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EINSTEIN Junior: Oral Rivaroxaban in Children With Venous Thrombosis (EINSTEIN Jr)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02234843
Recruitment Status : Completed
First Posted : September 9, 2014
Results First Posted : April 1, 2020
Last Update Posted : April 1, 2020
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Venous Thromboembolism
Interventions Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Standard of Care
Enrollment 500
Recruitment Details Study was conducted at 109 study centers in 28 countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Finland, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Portugal, Russia, Singapore, Slovakia, Spain, Sweden, Switzerland, Turkey, UK, and USA between 13 Nov 2014 and 30 Jan 2019.
Pre-assignment Details A total of 520 children were screened for this study. Twenty children did not pass the screen of inclusion/exclusion criteria. A total of 500 children were randomized 2:1 to study treatment.
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5 Comparator, Aged 12-<18 Comparator, Aged 6-<12 Comparator, Aged 2-<6 Comparator, Aged 0.5-<2 Comparator, Aged Birth-<0.5
Hide Arm/Group Description Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension. Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension. Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension. Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension. Children aged 12-<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to Vitamin K Antagonist (VKA) therapy. VKA dosages were adjusted to maintain the international normalized ratio (INR) within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Children aged 6-<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Children aged 2-<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Children aged 0.5-<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Children aged birth-<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Period Title: Overall Study
Started 184 67 47 21 16 92 34 22 9 8
Completed 162 61 44 16 14 79 32 20 8 8
Not Completed 22 6 3 5 2 13 2 2 1 0
Reason Not Completed
Death             1             0             0             0             0             0             0             0             0             0
Protocol Violation             1             0             1             0             0             0             0             0             0             0
Efficacy outcome reached             2             0             0             0             0             2             0             0             0             0
Patient convenience             2             0             0             0             0             1             0             0             0             0
Withdrawal by Subject             5             1             1             0             0             7             0             0             0             0
Recovery             1             0             0             0             0             0             0             0             0             0
Other             0             2             0             1             0             1             0             1             0             0
Physician Decision             4             1             0             1             0             0             0             1             0             0
Adverse Event             5             1             1             3             2             1             0             0             1             0
Non-compliance with study drug             1             0             0             0             0             1             1             0             0             0
Lost to Follow-up             0             1             0             0             0             0             1             0             0             0
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5 Comparator, Aged 12-<18 Comparator, Aged 6-<12 Comparator, Aged 2-<6 Comparator, Aged 0.5-<2 Comparator, Aged Birth-<0.5 Total
Hide Arm/Group Description Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension. Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension. Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension. Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension. Children aged 12-<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Children aged 6-<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Children aged 2-<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Children aged 0.5-<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Children aged birth-<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. Total of all reporting groups
Overall Number of Baseline Participants 184 67 47 21 16 92 34 22 9 8 500
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 184 participants 67 participants 47 participants 21 participants 16 participants 92 participants 34 participants 22 participants 9 participants 8 participants 500 participants
12-<18 years
184
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
92
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
276
  55.2%
6-<12 years
0
   0.0%
67
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
34
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
101
  20.2%
2-<6 years
0
   0.0%
0
   0.0%
47
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
22
 100.0%
0
   0.0%
0
   0.0%
69
  13.8%
0.5-<2 years
0
   0.0%
0
   0.0%
0
   0.0%
21
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
9
 100.0%
0
   0.0%
30
   6.0%
Birth-<0.5 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
16
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
8
 100.0%
24
   4.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 184 participants 67 participants 47 participants 21 participants 16 participants 92 participants 34 participants 22 participants 9 participants 8 participants 500 participants
Female
97
  52.7%
24
  35.8%
24
  51.1%
10
  47.6%
5
  31.3%
55
  59.8%
15
  44.1%
9
  40.9%
5
  55.6%
1
  12.5%
245
  49.0%
Male
87
  47.3%
43
  64.2%
23
  48.9%
11
  52.4%
11
  68.8%
37
  40.2%
19
  55.9%
13
  59.1%
4
  44.4%
7
  87.5%
255
  51.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 184 participants 67 participants 47 participants 21 participants 16 participants 92 participants 34 participants 22 participants 9 participants 8 participants 500 participants
Hispanic or Latino
164
  89.1%
58
  86.6%
42
  89.4%
15
  71.4%
12
  75.0%
79
  85.9%
26
  76.5%
19
  86.4%
8
  88.9%
6
  75.0%
429
  85.8%
Not Hispanic or Latino
7
   3.8%
5
   7.5%
1
   2.1%
3
  14.3%
1
   6.3%
6
   6.5%
5
  14.7%
1
   4.5%
0
   0.0%
0
   0.0%
29
   5.8%
Unknown or Not Reported
13
   7.1%
4
   6.0%
4
   8.5%
3
  14.3%
3
  18.8%
7
   7.6%
3
   8.8%
2
   9.1%
1
  11.1%
2
  25.0%
42
   8.4%
1.Primary Outcome
Title Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period
Hide Description The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
Time Frame During the main study treatment period (i.e., 3 months, except for children with central venous catheter venous thromboembolism (CVC-VTE) aged <2 years for whom it was 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Rivaroxaban Group Comparator Group
Hide Arm/Group Description:
Children randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux. Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children randomized to the comparator group will continue with UFH, LMWH or fondaparinux or may switch to VKA therapy. VKA dosages will be adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux can be discontinued once the INR is above 2.0 on two separate occasions, 24 hours apart
Overall Number of Participants Analyzed 335 165
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
1.2
(0.4 to 3.0)
3.0
(1.2 to 6.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban Group, Comparator Group
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1509
Comments [Not Specified]
Method Expl. Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
0.11 to 1.41
Estimation Comments [Not Specified]
2.Primary Outcome
Title Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period
Hide Description The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
Time Frame During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5 Comparator, Aged 12-<18 Comparator, Aged 6-<12 Comparator, Aged 2-<6 Comparator, Aged 0.5-<2 Comparator, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 12-<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 6-<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 2-<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 0.5-<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged birth-<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Overall Number of Participants Analyzed 184 67 47 21 16 92 34 22 9 8
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
2.2
(0.7 to 5.3)
0.0
(0.0 to 5.3)
0.0
(0.0 to 6.8)
0.0
(0.0 to 8.3)
0.0
(0.0 to 14.6)
3.3
(0.9 to 8.6)
2.9
(0.2 to 15.1)
4.5
(0.2 to 20.7)
0.0
(0.0 to 18.4)
0.0
(0.0 to 29.9)
3.Primary Outcome
Title Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period
Hide Description Incidence rates for all children except those aged < 2 years with catheter-related thrombosis. If no participant in the specific subgroup entered in the specific optional extension period, no analysis of an outcome was possible., The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference Population.
Time Frame During extended treatment period: up to month 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Rivaroxaban, Aged 12-<18 Comparator, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5 Comparator, Aged 6-<12 Comparator, Aged 2-<6 Comparator, Aged 0.5-<2 Comparator, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 12-<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 6-<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 2-<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 0.5-<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged birth-<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Overall Number of Participants Analyzed 93 46 21 19 0 2 8 7 1 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Extension 1 (month 3 to 6) Number Analyzed 93 participants 46 participants 21 participants 19 participants 0 participants 2 participants 8 participants 7 participants 1 participants 1 participants
0.0
(0.0 to 3.8)
2.2
(0.1 to 10.9)
0.0
(0.0 to 14.6)
0.0
(0.0 to 16.3)
0.0
(0.0 to 77.6)
0.0
(0.0 to 14.6)
0.0
(0.0 to 37.7)
0.0
(0.0 to 95.0)
0.0
(0.0 to 95.0)
Extension 2 (month 6 to 9) Number Analyzed 38 participants 19 participants 9 participants 6 participants 0 participants 0 participants 3 participants 3 participants 0 participants 0 participants
2.6
(0.1 to 13.4)
5.3
(0.3 to 24.4)
0.0
(0.0 to 29.9)
0.0
(0.0 to 40.2)
0.0
(0.0 to 63.2)
0.0
(0.0 to 77.6)
Extension 3 (month 9 to 12) Number Analyzed 26 participants 14 participants 3 participants 2 participants 0 participants 0 participants 1 participants 2 participants 0 participants 0 participants
0.0
(0.0 to 11.6)
0.0
(0.0 to 23.0)
0.0
(0.0 to 63.2)
0.0
(0.0 to 77.6)
0.0
(0.0 to 95.2)
0.0
(0.0 to 77.6)
4.Primary Outcome
Title Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication)
Hide Description The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Age group with primary efficacy outcome was reported.
Time Frame More than 2 and up to 30 days after stop of study medication
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Rivaroxaban, Aged 12-<18 Comparator, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5 Comparator, Aged 6-<12 Comparator, Aged 2-<6 Comparator, Aged 0.5-<2 Comparator, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 12-<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 6-<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 2-<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 0.5-<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged birth-<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Overall Number of Participants Analyzed 184 92 67 47 21 16 34 22 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period
Hide Description The Central independent adjudication committee (CIAC) classified bleeding as: Major bleeding defined as overt bleeding and: · associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact (visit or telephone call) with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life (such as loss of school days or hospitalization).
Time Frame During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (SAF)
Arm/Group Title Rivaroxaban Group Comparator Group
Hide Arm/Group Description:
Children randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux. Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children randomized to the comparator group will continue with UFH, LMWH or fondaparinux or may switch to VKA therapy. VKA dosages will be adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux can be discontinued once the INR is above 2.0 on two separate occasions, 24 hours apart
Overall Number of Participants Analyzed 329 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
3
(1.6 to 5.5)
1.9
(0.5 to 3.3)
6.Primary Outcome
Title Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period
Hide Description The Central independent adjudication committee (CIAC) classified bleeding as: Major bleeding defined as overt bleeding and: · associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact (visit or telephone call) with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life (such as loss of school days or hospitalization).
Time Frame During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (SAF)
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5 Comparator, Aged 12-<18 Comparator, Aged 6-<12 Comparator, Aged 2-<6 Comparator, Aged 0.5-<2 Comparator, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 12-<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 6-<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 2-<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 0.5-<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged birth-<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Overall Number of Participants Analyzed 180 67 46 21 15 89 34 22 9 8
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
1.7
(0.5 to 4.7)
3.0
(0.5 to 9.6)
6.5
(1.8 to 17.7)
4.8
(0.2 to 21.8)
6.7
(0.3 to 30.2)
2.2
(0.4 to 7.3)
0.0
(0.0 to 9.0)
0.0
(0.0 to 13.9)
11.1
(0.6 to 44.3)
0.0
(0.0 to 34.9)
7.Primary Outcome
Title Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period
Hide Description Incidence rates for all children except those aged < 2 years with catheter-related thrombosis. If no participant entered in the specific optional extension period, no analysis of an outcome was possible. The CIAC classified bleeding as: Major bleeding defined as overt bleeding and: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life.
Time Frame During extended treatment period: up to month 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (SAF)
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 0.5-<2 Comparator, Aged 12-<18 Comparator, Aged 0.5-<2 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged Birth-<0.5 Comparator, Aged 6-<12 Comparator, Aged 2-<6 Comparator, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 12-<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 0.5-<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 6-<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 2-<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged birth-<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Overall Number of Participants Analyzed 93 0 46 1 21 19 2 8 7 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Extension 1 (month 3 to 6) Number Analyzed 93 participants 0 participants 46 participants 1 participants 21 participants 19 participants 2 participants 8 participants 7 participants 1 participants
1.1
(0.1 to 5.3)
0.0
(0.0 to 6.9)
0.0
(0.0 to 95.0)
0.0
(0.0 to 14.6)
0.0
(0.0 to 16.3)
0.0
(0.0 to 77.6)
0.0
(0.0 to 34.9)
0.0
(0.0 to 37.7)
0.0
(0.0 to 95.0)
Extension 2 (month 6 to 9) Number Analyzed 38 participants 0 participants 19 participants 0 participants 9 participants 6 participants 0 participants 3 participants 2 participants 0 participants
2.6
(0.1 to 13.4)
5.3
(0.3 to 24.4)
0.0
(0.0 to 29.9)
0.0
(0.0 to 40.2)
0.0
(0.0 to 63.2)
0.0
(0.0 to 77.6)
Extension 3 (month 9 to 12) Number Analyzed 26 participants 0 participants 46 participants 0 participants 3 participants 2 participants 0 participants 1 participants 2 participants 0 participants
0.0
(0.0 to 11.6)
0.0
(0.0 to 23.0)
0.0
(0.0 to 63.2)
0.0
(0.0 to 77.6)
0.0
(0.0 to 95.0)
0.0
(0.0 to 77.6)
8.Secondary Outcome
Title Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period
Hide Description The secondary efficacy outcome defined as the composite of all symptomatic recurrent venous thromboembolism and asymptomatic deterioration on repeat imaging as assessed by central independent adjudication committee. (CIAC) Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
Time Frame During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS)
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5 Comparator, Aged 12-<18 Comparator, Aged 6-<12 Comparator, Aged 2-<6 Comparator, Aged 0.5-<2 Comparator, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 12-<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 6-<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 2-<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged 0.5-<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Children aged birth-<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart.
Overall Number of Participants Analyzed 184 67 47 21 16 92 34 22 9 8
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
2.2
(0.7 to 5.3)
0.0
(0.0 to 5.3)
2.1
(0.1 to 10.7)
0.0
(0.0 to 14.6)
0.0
(0.0 to 19.8)
4.3
(1.5 to 10.3)
2.9
(0.2 to 15.1)
4.5
(0.2 to 20.7)
0.0
(0.0 to 29.9)
0.0
(0.0 to 34.9)
9.Secondary Outcome
Title AUC(0-24)ss in Plasma
Hide Description AUC(0-24)ss: Area under the concentration vs. time curve from time 0 to 24 hours at steady state.
Time Frame over 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis set (PKS)
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 173 65 44 21 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram*hour per liter
2120
(26.4% to N/A)
1960
(31.7% to N/A)
2380
(40.7% to N/A)
1840
(36.4% to N/A)
1590
(29.6% to N/A)
10.Secondary Outcome
Title Cmax,ss in Plasma
Hide Description Maximum drug concentration in measured matrix at steady state during a dosage interval
Time Frame 0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours (one dosing interval in steady state)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis set (PKS)
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 173 65 44 21 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram per liter
237
(20.6% to N/A)
184
(36.2% to N/A)
182
(31.2% to N/A)
136
(29.4% to N/A)
119
(24.1% to N/A)
11.Secondary Outcome
Title Ctrough,ss in Plasma
Hide Description Ctrough,ss refers to the drug concentration at the end of the dosage interval at steady state
Time Frame 0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours(one sampling interval in steady state)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis set (PKS)
Arm/Group Title Rivaroxaban, Aged 12-<18 Rivaroxaban, Aged 6-<12 Rivaroxaban, Aged 2-<6 Rivaroxaban, Aged 0.5-<2 Rivaroxaban, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 173 65 44 21 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram per liter
20.7
(45.8% to N/A)
21.4
(62.7% to N/A)
31.6
(70.1% to N/A)
22.9
(68.6% to N/A)
18.5
(50.4% to N/A)
12.Secondary Outcome
Title Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
Hide Description Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
Time Frame Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 12-<18
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Overall Number of Participants Analyzed 156
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=156 Number Analyzed 156 participants
1.29  (0.28)
Day 30 (2.5-4h) n=150 Number Analyzed 150 participants
1.57  (0.36)
Day 60 (2-8h) n=156 Number Analyzed 156 participants
1.52  (0.29)
13.Secondary Outcome
Title Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Hide Description Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
Time Frame Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 6-<12
Hide Arm/Group Description:
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=18 Number Analyzed 18 participants
1.46  (0.25)
Day 30 (2.5-4h) n=20 Number Analyzed 20 participants
1.67  (0.39)
Day 60 (2-8h) n=20 Number Analyzed 20 participants
1.52  (0.33)
14.Secondary Outcome
Title Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Hide Description Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
Time Frame Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 6-<12
Hide Arm/Group Description:
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=33 Number Analyzed 33 participants
1.17  (0.23)
Day 30 (2.5-4h) n=33 Number Analyzed 33 participants
1.26  (0.22)
Day 60 (2-8h) n=34 Number Analyzed 34 participants
1.21  (0.19)
15.Secondary Outcome
Title Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
Hide Description Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
Time Frame Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 2-<6
Hide Arm/Group Description:
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=1 Number Analyzed 1 participants
0.99 [1]   (NA)
Day 30 (2.5-4h) n=34 Number Analyzed 34 participants
1.36  (0.28)
Day 60 (2-8h) n=32 Number Analyzed 32 participants
1.33  (0.26)
[1]
'NA' denotes data that cannot be calculated.
16.Secondary Outcome
Title Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
Hide Description Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
Time Frame Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 0.5-<2
Hide Arm/Group Description:
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=0 Number Analyzed 0 participants
Day 30 (2.5-4h) n=1 Number Analyzed 1 participants
1.41 [1]   (NA)
Day 60 (2-8h) n=2 Number Analyzed 2 participants
1.05  (0.17)
[1]
'NA' denotes data that cannot be calculated.
17.Secondary Outcome
Title Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
Hide Description Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
Time Frame Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 2-<6
Hide Arm/Group Description:
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-3h) n=4 1.87  (1.09)
Day 60 (2-6h) n=4 1.32  (0.12)
18.Secondary Outcome
Title Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
Hide Description Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
Time Frame Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 0.5-<2
Hide Arm/Group Description:
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: ratios
Day 30 (0.5-3h) n=9 Number Analyzed 9 participants
1.25  (0.18)
Day 60 (2-6h) n=7 Number Analyzed 7 participants
2.00  (2.22)
19.Secondary Outcome
Title Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
Hide Description Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds.
Time Frame Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-3h) n=11 Number Analyzed 11 participants
1.35  (0.20)
Day 60 (2-6h) n=4 Number Analyzed 4 participants
1.45  (0.16)
20.Secondary Outcome
Title Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
Hide Description The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time Frame Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 12-<18
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Overall Number of Participants Analyzed 154
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=154 Number Analyzed 154 participants
1.17  (0.28)
Day 30 (2.5-4h) n=149 Number Analyzed 149 participants
1.38  (0.50)
Day 60 (2-8h) n=153 Number Analyzed 153 participants
1.33  (0.38)
21.Secondary Outcome
Title Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Hide Description The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time Frame Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 6-<12
Hide Arm/Group Description:
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=17 Number Analyzed 17 participants
1.27  (0.20)
Day 30 (2.5-4h) n=17 Number Analyzed 17 participants
1.39  (0.26)
Day 60 (2-8h) n=19 Number Analyzed 19 participants
1.24  (0.20)
22.Secondary Outcome
Title Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Hide Description The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time Frame Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 6-<12
Hide Arm/Group Description:
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=30 Number Analyzed 30 participants
1.11  (0.24)
Day 30 (2.5-4h) n=30 Number Analyzed 30 participants
1.15  (0.22)
Day 60 (2-8h) n=31 Number Analyzed 31 participants
1.18  (0.24)
23.Secondary Outcome
Title Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
Hide Description The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
Time Frame Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 2-<6
Hide Arm/Group Description:
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 32
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=1 Number Analyzed 1 participants
0.90 [1]   (NA)
Day 30 (2.5-4h) n=32 Number Analyzed 32 participants
1.29  (0.33)
Day 60 (2-8h) n=29 Number Analyzed 29 participants
1.23  (0.21)
[1]
'NA' denotes data that cannot be calculated.
24.Secondary Outcome
Title Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
Hide Description The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
Time Frame Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 0.5-<2
Hide Arm/Group Description:
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-1.5h) n=0 Number Analyzed 0 participants
Day 30 (2.5-4h) n=1 Number Analyzed 1 participants
1.13 [1]   (NA)
Day 60 (2-8h) n=2 Number Analyzed 2 participants
1.10  (0.02)
[1]
'NA' denotes data that cannot be calculated.
25.Secondary Outcome
Title Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
Hide Description The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time Frame Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 2-<6
Hide Arm/Group Description:
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-3h) n=4 1.50  (0.83)
Day 60 (2-6h) n=4 1.13  (0.06)
26.Secondary Outcome
Title Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
Hide Description The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time Frame Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 0.5-<2
Hide Arm/Group Description:
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-3h) n=9 Number Analyzed 9 participants
1.20  (0.39)
Day 60 (2-6h) n=6 Number Analyzed 6 participants
1.10  (0.47)
27.Secondary Outcome
Title Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
Hide Description The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time Frame Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: ratio
Day 30 (0.5-3h) n=9 Number Analyzed 9 participants
1.31  (0.15)
Day 60 (2-6h) n=3 Number Analyzed 3 participants
1.21  (0.16)
28.Secondary Outcome
Title Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
Hide Description This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time Frame Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 24 hours on Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 12-<18
Hide Arm/Group Description:
Children aged 12-<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension.
Overall Number of Participants Analyzed 167
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Day 30 (0.5-1.5h) n=141 Number Analyzed 141 participants
164.46  (124.46)
Day 30 (2.5-4h) n=164 Number Analyzed 164 participants
254.66  (188.64)
Day 60 (2-8h) n=167 Number Analyzed 167 participants
255.40  (171.59)
Day 90 (20-24h) n=58 Number Analyzed 58 participants
62.12  (175.87)
29.Secondary Outcome
Title Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Hide Description This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time Frame Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 24 hours on Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 6-<12
Hide Arm/Group Description:
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Day 30 (0.5-1.5h) n=22 Number Analyzed 22 participants
206.89  (105.01)
Day 30 (2.5-4h) n=23 Number Analyzed 23 participants
263.24  (156.73)
Day 60 (2-8h) n=22 Number Analyzed 22 participants
243.45  (124.92)
Day 90 (20-24h) n=9 Number Analyzed 9 participants
27.39  (14.66)
30.Secondary Outcome
Title Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
Hide Description This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time Frame Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 16 hours on Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 6-<12
Hide Arm/Group Description:
Children aged 6-<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Day 30 (0.5-1.5h) n=37 Number Analyzed 37 participants
96.82  (76.77)
Day 30 (2.5-4h) n=36 Number Analyzed 36 participants
139.10  (102.19)
Day 60 (2-8h) n=35 Number Analyzed 35 participants
126.53  (81.78)
Day 90 (10-16h) n=20 Number Analyzed 20 participants
47.49  (66.88)
31.Secondary Outcome
Title Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
Hide Description This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time Frame Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 16 hours on Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 2-<6
Hide Arm/Group Description:
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Day 30 (2.5-4h) n=37 Number Analyzed 37 participants
177.78  (147.29)
Day 60 (2-8h) n=36 Number Analyzed 36 participants
150.03  (95.77)
Day 90 (10-16h) n=18 Number Analyzed 18 participants
54.40  (51.52)
32.Secondary Outcome
Title Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
Hide Description This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
Time Frame Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 0.5-<2
Hide Arm/Group Description:
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Day 30 (0.5-1.5h) n=1 Number Analyzed 1 participants
247.54 [1]   (NA)
Day 30 (2.5-4h) n=2 Number Analyzed 2 participants
160.71  (153.84)
Day 60 (2-8h) n=4 Number Analyzed 4 participants
121.09  (81.94)
[1]
'NA' denotes data that cannot be calculated.
33.Secondary Outcome
Title Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
Hide Description This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
Time Frame Up to 3 hours post dose on Day 30, up to 6 hours post dose on Day 60, and up to 16 hours on Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 2-<6
Hide Arm/Group Description:
Children aged 2-<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Day 30 (0.5-3h) n=4 Number Analyzed 4 participants
209.67  (127.86)
Day 60 (2-6h) n=4 Number Analyzed 4 participants
140.46  (78.82)
Day 90 (10-16h) n=1 Number Analyzed 1 participants
62.56 [1]   (NA)
[1]
'NA' denotes data that cannot be calculated.
34.Secondary Outcome
Title Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
Hide Description This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
Time Frame Up to 3 hours post dose on Day 30, up to 6 hours post dose on Day 60, up to 16 hours on Day 90 and follow-up up to 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged 0.5-<2
Hide Arm/Group Description:
Children aged 0.5-<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Day 30 (0.5-3h) n=12 Number Analyzed 12 participants
111.35  (97.03)
Day 30 (2-6h) n=11 Number Analyzed 11 participants
147.24  (125.40)
Day 90 (10-16h) n=3 Number Analyzed 3 participants
23.40  (4.51)
Follow-up n=1 Number Analyzed 1 participants
71.30 [1]   (NA)
[1]
'NA' denotes data that cannot be calculated.
35.Secondary Outcome
Title Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
Hide Description This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time Frame Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
Arm/Group Title Rivaroxaban, Aged Birth-<0.5
Hide Arm/Group Description:
Children aged birth-<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of < 20 kg received rivaroxaban as oral suspension.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Day 30 (0.5-3h) n=10 Number Analyzed 10 participants
118.12  (82.08)
Day 60 (2-6h) n=5 Number Analyzed 5 participants
228.03  (181.08)
Time Frame After randomization until last intake of study medication plus 2 days, up to 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Comparator Group Rivaroxaban Group
Hide Arm/Group Description Children randomized to the comparator group will continue with UFH, LMWH or fondaparinux or may switch to VKA therapy. VKA dosages will be adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux can be discontinued once the INR is above 2.0 on two separate occasions, 24 hours apart Children randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux. Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of < 20 kg received rivaroxaban as oral suspension.
All-Cause Mortality
Comparator Group Rivaroxaban Group
Affected / at Risk (%) Affected / at Risk (%)
Total   0/162 (0.00%)      2/329 (0.61%)    
Hide Serious Adverse Events
Comparator Group Rivaroxaban Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/162 (21.60%)      78/329 (23.71%)    
Blood and lymphatic system disorders     
Febrile neutropenia * 1  1/162 (0.62%)  1 8/329 (2.43%)  9
Lymphadenopathy * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Pancytopenia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Sickle cell anaemia with crisis * 1  1/162 (0.62%)  2 0/329 (0.00%)  0
Thrombocytopenia * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Bone marrow failure * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Cardiac disorders     
Atrial tachycardia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Cardiac failure * 1  0/162 (0.00%)  0 1/329 (0.30%)  2
Low cardiac output syndrome * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Pericardial effusion * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Postural orthostatic tachycardia syndrome * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Congenital, familial and genetic disorders     
Muscular dystrophy * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Ear and labyrinth disorders     
Vertigo * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Eye disorders     
Papilloedema * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Retinal haemorrhage * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Gastrointestinal disorders     
Abdominal pain * 1  1/162 (0.62%)  1 3/329 (0.91%)  3
Enterocolitis haemorrhagic * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Gastric haemorrhage * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Intestinal dilatation * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Pancreatitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Small intestinal obstruction * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Vomiting * 1  0/162 (0.00%)  0 6/329 (1.82%)  6
Faecaloma * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Paraesthesia oral * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
General disorders     
Chest pain * 1  1/162 (0.62%)  1 2/329 (0.61%)  2
Pyrexia * 1  2/162 (1.23%)  3 6/329 (1.82%)  6
Peripheral swelling * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Hepatobiliary disorders     
Drug-induced liver injury * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Immune system disorders     
Autoimmune disorder * 1  0/162 (0.00%)  0 1/329 (0.30%)  3
Infections and infestations     
Bacteraemia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Bronchiolitis * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Eczema herpeticum * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Gastroenteritis * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Gastroenteritis rotavirus * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Gastroenteritis viral * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Herpes zoster * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Mastoiditis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Meningitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Meningitis bacterial * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Nasopharyngitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Osteomyelitis * 1  0/162 (0.00%)  0 2/329 (0.61%)  3
Peritonitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Pneumonia viral * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Pyoderma streptococcal * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Tonsillitis streptococcal * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Urinary tract infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Varicella * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Viral infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Viral upper respiratory tract infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Wound infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Gastritis viral * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Bacterial sepsis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Implant site infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Parainfluenzae virus infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Device related infection * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Gastroenteritis norovirus * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Infected dermal cyst * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Candida infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Injury, poisoning and procedural complications     
Accidental overdose * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Subdural haemorrhage * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Traumatic fracture * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Post lumbar puncture syndrome * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Procedural pain * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Procedural haemorrhage * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Traumatic haemothorax * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Accidental underdose * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Incorrect route of product administration * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Investigations     
Alanine aminotransferase increased * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Aspartate aminotransferase increased * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Blood bilirubin increased * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Oxygen saturation decreased * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Drug clearance decreased * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Gastrointestinal stoma output decreased * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Metabolism and nutrition disorders     
Acidosis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Dehydration * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Fluid overload * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Hyponatraemia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Metabolic acidosis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Musculoskeletal and connective tissue disorders     
Back pain * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Pain in extremity * 1  0/162 (0.00%)  0 3/329 (0.91%)  3
Joint range of motion decreased * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Craniopharyngioma * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Myxofibrosarcoma * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Nervous system disorders     
Cerebral infarction * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Dizziness * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Dysaesthesia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Epilepsy * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Headache * 1  3/162 (1.85%)  3 2/329 (0.61%)  2
Hemiparesis * 1  0/162 (0.00%)  0 1/329 (0.30%)  2
Intracranial pressure increased * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Neuralgia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Paraesthesia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Seizure * 1  2/162 (1.23%)  2 1/329 (0.30%)  1
Syncope * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Sciatic nerve neuropathy * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Encephalitis autoimmune * 1  1/162 (0.62%)  2 0/329 (0.00%)  0
Hemianaesthesia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Hemiparaesthesia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Product Issues     
Device malfunction * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Psychiatric disorders     
Confusional state * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Drug abuse * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Renal and urinary disorders     
Haematuria * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
IgA nephropathy * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Nephrolithiasis * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Nephropathy * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Nephrotic syndrome * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Urinary bladder haemorrhage * 1  0/162 (0.00%)  0 1/329 (0.30%)  2
Urinary retention * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Renal impairment * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Acute kidney injury * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Reproductive system and breast disorders     
Menorrhagia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Haemorrhagic ovarian cyst * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Respiratory, thoracic and mediastinal disorders     
Diaphragmatic paralysis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Hypoxia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Pleural effusion * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Pneumonitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Respiratory distress * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Respiratory failure * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Pulmonary vein stenosis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Bronchopneumopathy * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Laryngeal haemorrhage * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Skin and subcutaneous tissue disorders     
Rash * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Surgical and medical procedures     
Colostomy * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Mastoidectomy * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Sclerotherapy * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Lumboperitoneal shunt * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Faecal disimpaction * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Vascular disorders     
Haematoma * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Haemorrhage * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
1
Term from vocabulary, MedDRA 21.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Comparator Group Rivaroxaban Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   121/162 (74.69%)      275/329 (83.59%)    
Blood and lymphatic system disorders     
Anaemia * 1  5/162 (3.09%)  5 11/329 (3.34%)  20
Coagulopathy * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Febrile neutropenia * 1  0/162 (0.00%)  0 3/329 (0.91%)  3
Haemolysis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Increased tendency to bruise * 1  3/162 (1.85%)  3 1/329 (0.30%)  1
Iron deficiency anaemia * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Leukocytosis * 1  0/162 (0.00%)  0 2/329 (0.61%)  3
Leukopenia * 1  1/162 (0.62%)  1 4/329 (1.22%)  8
Lymphadenitis * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Lymphadenopathy * 1  2/162 (1.23%)  2 2/329 (0.61%)  2
Lymphopenia * 1  0/162 (0.00%)  0 1/329 (0.30%)  5
Neutropenia * 1  4/162 (2.47%)  4 6/329 (1.82%)  7
Pancytopenia * 1  2/162 (1.23%)  2 1/329 (0.30%)  1
Thrombocytopenia * 1  2/162 (1.23%)  2 10/329 (3.04%)  15
Thrombocytosis * 1  1/162 (0.62%)  2 1/329 (0.30%)  2
Autoimmune neutropenia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Haemorrhagic diathesis * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Bone marrow failure * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Cytopenia * 1  1/162 (0.62%)  2 0/329 (0.00%)  0
Cardiac disorders     
Atrial tachycardia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Bradycardia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Palpitations * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Sinus tachycardia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Supraventricular tachycardia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Tachycardia * 1  0/162 (0.00%)  0 6/329 (1.82%)  6
Congenital, familial and genetic disorders     
Hydrocele * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Immunodeficiency congenital * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Protein S deficiency * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Ear and labyrinth disorders     
Conductive deafness * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Deafness * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Ear haemorrhage * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Ear pain * 1  1/162 (0.62%)  1 6/329 (1.82%)  7
Deafness unilateral * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Ear discomfort * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Ear pruritus * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Endocrine disorders     
Cushingoid * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Eye disorders     
Amblyopia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Astigmatism * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Cataract * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Diplopia * 1  1/162 (0.62%)  1 2/329 (0.61%)  2
Eye inflammation * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Eye irritation * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Eye pain * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Eye swelling * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Eyelid ptosis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Glaucoma * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Heterophoria * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Myopia * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Ocular hyperaemia * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Ocular hypertension * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Optic disc haemorrhage * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Papilloedema * 1  3/162 (1.85%)  3 4/329 (1.22%)  5
Photophobia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Retinal haemorrhage * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Strabismus * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Vision blurred * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Visual impairment * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Conjunctival hyperaemia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Eye pruritus * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Gastrointestinal disorders     
Abdominal discomfort * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Abdominal distension * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Abdominal pain * 1  9/162 (5.56%)  11 17/329 (5.17%)  27
Abdominal pain upper * 1  4/162 (2.47%)  4 11/329 (3.34%)  12
Anal fissure * 1  0/162 (0.00%)  0 1/329 (0.30%)  4
Anal fistula * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Aphthous ulcer * 1  0/162 (0.00%)  0 3/329 (0.91%)  3
Breath odour * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Constipation * 1  10/162 (6.17%)  10 8/329 (2.43%)  11
Dental caries * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Diarrhoea * 1  11/162 (6.79%)  12 25/329 (7.60%)  30
Diarrhoea haemorrhagic * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Dry mouth * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Dyspepsia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Faeces discoloured * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Flatulence * 1  2/162 (1.23%)  2 0/329 (0.00%)  0
Food poisoning * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Gastric haemorrhage * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Gastritis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Gastrooesophageal reflux disease * 1  1/162 (0.62%)  1 3/329 (0.91%)  3
Gastrointestinal disorder * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Gingival bleeding * 1  1/162 (0.62%)  1 13/329 (3.95%)  13
Gingival pain * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Glossitis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Haematemesis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Haematochezia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Mouth haemorrhage * 1  0/162 (0.00%)  0 6/329 (1.82%)  6
Mouth ulceration * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Nausea * 1  6/162 (3.70%)  7 22/329 (6.69%)  25
Oral pain * 1  2/162 (1.23%)  2 0/329 (0.00%)  0
Rectal haemorrhage * 1  3/162 (1.85%)  3 7/329 (2.13%)  8
Stomatitis * 1  1/162 (0.62%)  1 4/329 (1.22%)  7
Tongue blistering * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Tongue coated * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Tongue geographic * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Tongue ulceration * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Toothache * 1  2/162 (1.23%)  2 3/329 (0.91%)  4
Vomiting * 1  13/162 (8.02%)  17 36/329 (10.94%)  42
Anal haemorrhage * 1  0/162 (0.00%)  0 3/329 (0.91%)  3
Anal inflammation * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Large intestinal haemorrhage * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Perianal erythema * 1  0/162 (0.00%)  0 1/329 (0.30%)  2
Faecaloma * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Abdominal hernia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Appendix disorder * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Gastrointestinal inflammation * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Tooth socket haemorrhage * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Anorectal discomfort * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Anal incontinence * 1  0/162 (0.00%)  0 1/329 (0.30%)  2
General disorders     
Asthenia * 1  1/162 (0.62%)  1 3/329 (0.91%)  5
Chest discomfort * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Chest pain * 1  5/162 (3.09%)  6 16/329 (4.86%)  18
Cyst * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Fatigue * 1  6/162 (3.70%)  6 21/329 (6.38%)  23
Feeling abnormal * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Feeling cold * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Gait disturbance * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Granuloma * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Hyperthermia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Hypothermia * 1  2/162 (1.23%)  2 0/329 (0.00%)  0
Influenza like illness * 1  1/162 (0.62%)  1 2/329 (0.61%)  2
Injection site bruising * 1  8/162 (4.94%)  8 0/329 (0.00%)  0
Injection site extravasation * 1  1/162 (0.62%)  2 0/329 (0.00%)  0
Injection site haematoma * 1  3/162 (1.85%)  3 0/329 (0.00%)  0
Injection site haemorrhage * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Injection site induration * 1  1/162 (0.62%)  3 0/329 (0.00%)  0
Injection site mass * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Injection site pruritus * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Malaise * 1  2/162 (1.23%)  2 1/329 (0.30%)  1
Mucosal inflammation * 1  0/162 (0.00%)  0 4/329 (1.22%)  4
Oedema * 1  0/162 (0.00%)  0 3/329 (0.91%)  3
Oedema peripheral * 1  1/162 (0.62%)  1 4/329 (1.22%)  4
Pain * 1  0/162 (0.00%)  0 7/329 (2.13%)  7
Pyrexia * 1  14/162 (8.64%)  22 37/329 (11.25%)  51
Application site vesicles * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Peripheral swelling * 1  4/162 (2.47%)  5 5/329 (1.52%)  5
Catheter site haemorrhage * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Puncture site haemorrhage * 1  5/162 (3.09%)  8 1/329 (0.30%)  1
Catheter site pain * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Catheter site rash * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Vessel puncture site haemorrhage * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Nodule * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Non-cardiac chest pain * 1  2/162 (1.23%)  2 0/329 (0.00%)  0
Application site hypersensitivity * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Infusion site extravasation * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Vaccination site pain * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Medical device site haemorrhage * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Hepatobiliary disorders     
Cholangitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Cholelithiasis * 1  2/162 (1.23%)  2 1/329 (0.30%)  1
Gallbladder disorder * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Hepatic function abnormal * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Hypertransaminasaemia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Immune system disorders     
Allergy to animal * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Anaphylactic reaction * 1  1/162 (0.62%)  2 0/329 (0.00%)  0
Hypogammaglobulinaemia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Serum sickness * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Seasonal allergy * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Secondary immunodeficiency * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Allergy to arthropod sting * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Graft versus host disease in skin * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Graft versus host disease in liver * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Acute graft versus host disease in skin * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Infections and infestations     
Angular cheilitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Bacteriuria * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Bronchiolitis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Bronchitis * 1  0/162 (0.00%)  0 4/329 (1.22%)  4
Cellulitis * 1  2/162 (1.23%)  2 1/329 (0.30%)  1
Conjunctivitis * 1  2/162 (1.23%)  2 3/329 (0.91%)  4
Ear infection * 1  1/162 (0.62%)  1 3/329 (0.91%)  3
Eye infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Eyelid infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Folliculitis * 1  2/162 (1.23%)  2 2/329 (0.61%)  2
Gastroenteritis * 1  0/162 (0.00%)  0 7/329 (2.13%)  7
Gastroenteritis viral * 1  0/162 (0.00%)  0 4/329 (1.22%)  4
Gastrointestinal infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Giardiasis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Hand-foot-and-mouth disease * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Herpes virus infection * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Herpes zoster * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Hordeolum * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Impetigo * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Influenza * 1  3/162 (1.85%)  4 6/329 (1.82%)  6
Injection site infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Localised infection * 1  0/162 (0.00%)  0 3/329 (0.91%)  4
Mastoiditis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Nasopharyngitis * 1  10/162 (6.17%)  13 29/329 (8.81%)  36
Oral candidiasis * 1  1/162 (0.62%)  1 5/329 (1.52%)  5
Osteomyelitis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Otitis media * 1  1/162 (0.62%)  1 3/329 (0.91%)  3
Otitis media acute * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Otitis media chronic * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Paronychia * 1  1/162 (0.62%)  1 3/329 (0.91%)  3
Periodontitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Pharyngitis * 1  4/162 (2.47%)  4 2/329 (0.61%)  2
Pharyngitis streptococcal * 1  1/162 (0.62%)  3 2/329 (0.61%)  2
Pneumonia * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Pneumonia mycoplasmal * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Postoperative wound infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Rhinitis * 1  4/162 (2.47%)  4 11/329 (3.34%)  12
Scarlet fever * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Sinusitis * 1  1/162 (0.62%)  1 6/329 (1.82%)  6
Skin infection * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Subcutaneous abscess * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Tonsillitis * 1  4/162 (2.47%)  4 5/329 (1.52%)  5
Tooth abscess * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Upper respiratory tract infection * 1  8/162 (4.94%)  8 10/329 (3.04%)  13
Urethritis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Urinary tract infection * 1  2/162 (1.23%)  2 4/329 (1.22%)  4
Varicella * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Viral infection * 1  1/162 (0.62%)  1 4/329 (1.22%)  4
Viral pharyngitis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Viral rash * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Viral upper respiratory tract infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Vulvitis * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Vulvovaginal candidiasis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Wound infection * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Oral infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Tooth infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Abscess limb * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Staphylococcal bacteraemia * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Escherichia urinary tract infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Cardiac infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Tinea versicolour * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Asymptomatic bacteriuria * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Catheter site infection * 1  1/162 (0.62%)  1 2/329 (0.61%)  2
Enteritis infectious * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Implant site infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Sinusitis bacterial * 1  0/162 (0.00%)  0 1/329 (0.30%)  2
Adenovirus infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Bacterial infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Mastoid abscess * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Respiratory syncytial virus infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Ear infection viral * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Parainfluenzae virus infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Respiratory tract infection viral * 1  0/162 (0.00%)  0 1/329 (0.30%)  2
Respiratory tract infection * 1  0/162 (0.00%)  0 3/329 (0.91%)  3
Acarodermatitis * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Device related infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Vulvovaginal mycotic infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Oral herpes * 1  0/162 (0.00%)  0 4/329 (1.22%)  5
Gastrointestinal viral infection * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Candida infection * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Injury, poisoning and procedural complications     
Accidental overdose * 1  0/162 (0.00%)  0 7/329 (2.13%)  7
Alcohol poisoning * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Arthropod bite * 1  1/162 (0.62%)  1 2/329 (0.61%)  2
Concussion * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Fall * 1  2/162 (1.23%)  2 5/329 (1.52%)  6
Foot fracture * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Greenstick fracture * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Hand fracture * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Head injury * 1  3/162 (1.85%)  3 2/329 (0.61%)  4
Joint dislocation * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Ligament sprain * 1  3/162 (1.85%)  3 1/329 (0.30%)  1
Overdose * 1  0/162 (0.00%)  0 2/329 (0.61%)  2
Road traffic accident * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Subcutaneous haematoma * 1  5/162 (3.09%)  5 14/329 (4.26%)  21
Tibia fracture * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Transfusion reaction * 1  1/162 (0.62%)  1 2/329 (0.61%)  3
Wound secretion * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Mouth injury * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Exposure to communicable disease * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Muscle strain * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Contusion * 1  9/162 (5.56%)  10 15/329 (4.56%)  19
Incision site haemorrhage * 1  0/162 (0.00%)  0 4/329 (1.22%)  4
Wound haemorrhage * 1  2/162 (1.23%)  3 13/329 (3.95%)  14
Thermal burn * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Postoperative thoracic procedure complication * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Underdose * 1  0/162 (0.00%)  0 3/329 (0.91%)  3
Post procedural complication * 1  0/162 (0.00%)  0 1/329 (0.30%)  1
Stoma site rash * 1  1/162 (0.62%)  1 1/329 (0.30%)  1
Incision site haematoma * 1  1/162 (0.62%)  1 0/329 (0.00%)  0
Joint injury * 1  1/162 (0.62%)  1 0/329 (0.00%)  0