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Trial record 93 of 733 for:    warfarin

Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation (TripleAXEL)

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ClinicalTrials.gov Identifier: NCT02042534
Recruitment Status : Completed
First Posted : January 23, 2014
Results First Posted : February 8, 2017
Last Update Posted : February 8, 2017
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Sun U. Kwon, Asan Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Ischemic Stroke
Transient Ischemic Attack
Interventions Drug: Rivaroxaban
Drug: Warfarin
Enrollment 195
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rivaroxaban Warfarin
Hide Arm/Group Description

Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.

Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 – 3.0].

Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Period Title: Overall Study
Started 101 94
Completed 101 94
Not Completed 0 0
Arm/Group Title Rivaroxaban Warfarin Total
Hide Arm/Group Description

Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.

Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 – 3.0].

Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Total of all reporting groups
Overall Number of Baseline Participants 95 88 183
Hide Baseline Analysis Population Description
Modified Intention-to-treat analysis : The subject who is measured for the primary end point with IP is administered more than at least once after randomization
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 95 participants 88 participants 183 participants
70.2  (10.1) 70.6  (10.9) 70.4  (10.4)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 88 participants 183 participants
Female
40
  42.1%
36
  40.9%
76
  41.5%
Male
55
  57.9%
52
  59.1%
107
  58.5%
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/㎡
Number Analyzed 95 participants 88 participants 183 participants
24.4  (3.3) 23.6  (3.1) 24.0  (3.2)
1.Primary Outcome
Title Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging
Hide Description

Intracranial bleeding: symptomatic hemorrhage confirmed by CT or MRI or asymptomatic hemorrhage on follow-up GRE or SWI imaging at 1 month

Recurrent ischemic lesion: symptomatic ischemic stroke confirmed by relevant neuroimagings or asymptomatic recurrent ischemic lesion on follow-up or FLAIR imaging at 1 month

Time Frame 1 month after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
  • modified Intention to treat: 95 / 88 (Rivaroxaban/Warfarin)
  • Per protocol: 93 / 87 (Rivaroxaban/Warfarin)
  • Safety: 98 / 90 (Rivaroxaban/Warfarin)
Arm/Group Title Rivaroxaban Warfarin
Hide Arm/Group Description:

Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.

Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 – 3.0].

Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Overall Number of Participants Analyzed 95 88
Measure Type: Number
Unit of Measure: Participants
47 48
2.Secondary Outcome
Title The Number of Patients With Intracranial Bleeding
Hide Description Intracranial bleeding confirmed by relevant neuroimagings
Time Frame at 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT
Arm/Group Title Rivaroxaban Warfarin
Hide Arm/Group Description:

Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.

Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 – 3.0].

Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Overall Number of Participants Analyzed 95 88
Measure Type: Number
Unit of Measure: Participants
30 25
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6765
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
3.Secondary Outcome
Title The Number of Patients With Recurrent Ischemic Lesion
Hide Description Recurrent ischemic lesion confirmed by relevant neuroimagings
Time Frame at 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT
Arm/Group Title Rivaroxaban Warfarin
Hide Arm/Group Description:

Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.

Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 – 3.0].

Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Overall Number of Participants Analyzed 98 88
Measure Type: Number
Unit of Measure: Participants
28 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3753
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
4.Secondary Outcome
Title Length of Hospitalization
Hide Description Time to event will be calculated
Time Frame at 1month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rivaroxaban Warfarin
Hide Arm/Group Description:

Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.

Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 – 3.0].

Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Overall Number of Participants Analyzed 94 88
Mean (Standard Deviation)
Unit of Measure: days
4.6  (3.9) 5.6  (4.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon rank sum test
5.Secondary Outcome
Title Number of Participants With Modified Rankin Score of 0 or 1 at Week 4
Hide Description

modified Rankin Score

0 : No symptoms at all

  1. : No significant disability despite symptoms; able to carry out all usual duties and activities
  2. : Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
  3. : Moderate disability; requiring some help, but able to walk without assistance
  4. : Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
  5. : Severe disability; bedridden, incontinent and requiring constant nursing care and attention
  6. : Dead
Time Frame at 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT (mRS 0,1 at Week 4, n(%)
Arm/Group Title Rivaroxaban Warfarin
Hide Arm/Group Description:

Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.

Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 – 3.0].

Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Overall Number of Participants Analyzed 95 88
Measure Type: Number
Unit of Measure: participants
79 64
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban, Warfarin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3301
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rivaroxaban Warfarin
Hide Arm/Group Description

Safety population : 98 (patients)

Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.

Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

Safety population : 90 (patients)

Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 – 3.0].

Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

All-Cause Mortality
Rivaroxaban Warfarin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Rivaroxaban Warfarin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/98 (6.12%)      5/90 (5.56%)    
Cardiac disorders     
Atrial fibrillation  1  1/98 (1.02%)  1 0/90 (0.00%)  0
Ear and labyrinth disorders     
Vertigo positional  1  0/98 (0.00%)  0 1/90 (1.11%)  1
Gastrointestinal disorders     
Gastrooesophageal reflux disease  1  1/98 (1.02%)  1 0/90 (0.00%)  0
Large intestine polyp  1  1/98 (1.02%)  1 0/90 (0.00%)  0
Investigations     
International normalised ratio increased  1  1/98 (1.02%)  1 0/90 (0.00%)  0
Laboratory test abnormal  1  0/98 (0.00%)  0 1/90 (1.11%)  1
Musculoskeletal and connective tissue disorders     
Arthritis  1  0/98 (0.00%)  0 1/90 (1.11%)  1
Nervous system disorders     
Cerebral infarction  1  1/98 (1.02%)  1 1/90 (1.11%)  1
Stroke in evolution  1  1/98 (1.02%)  1 0/90 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary hypertension  1  0/98 (0.00%)  0 1/90 (1.11%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rivaroxaban Warfarin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   46/98 (46.94%)      51/90 (56.67%)    
Blood and lymphatic system disorders     
Anaemia  1  2/98 (2.04%)  2 0/90 (0.00%)  0
Gastrointestinal disorders     
Constipation  1  4/98 (4.08%)  4 6/90 (6.67%)  6
Nausea  1  3/98 (3.06%)  3 1/90 (1.11%)  1
Infections and infestations     
Nasopharyngitis  1  0/98 (0.00%)  0 2/90 (2.22%)  2
Investigations     
International normalised ratio increased  1  1/98 (1.02%)  1 6/90 (6.67%)  6
Metabolism and nutrition disorders     
Decreased appetite  1  0/98 (0.00%)  0 3/90 (3.33%)  3
Musculoskeletal and connective tissue disorders     
Musculoskeletal pain  1  2/98 (2.04%)  2 4/90 (4.44%)  5
Nervous system disorders     
Dizziness  1  3/98 (3.06%)  3 8/90 (8.89%)  9
Psychiatric disorders     
Delirium  1  0/98 (0.00%)  0 2/90 (2.22%)  2
Depression  1  1/98 (1.02%)  1 3/90 (3.33%)  3
Insomnia  1  1/98 (1.02%)  1 2/90 (2.22%)  2
Social circumstances     
Others  1  24/98 (24.49%)  68 12/90 (13.33%)  103
Vascular disorders     
Hypertension  1  4/98 (4.08%)  5 0/90 (0.00%)  0
Hypotension  1  1/98 (1.02%)  1 2/90 (2.22%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sun U. Kwon, MD, PhD, Prof
Organization: Asan Medical Center, University of Ulsan
Phone: 82-2-3010-3960
EMail: sukwon@amc.seoul.kr
Layout table for additonal information
Responsible Party: Sun U. Kwon, Asan Medical Center
ClinicalTrials.gov Identifier: NCT02042534     History of Changes
Other Study ID Numbers: LMI-2013-1013
First Submitted: January 17, 2014
First Posted: January 23, 2014
Results First Submitted: August 8, 2016
Results First Posted: February 8, 2017
Last Update Posted: February 8, 2017