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Treatment of Thrombocytopenia in Patients With Chronic Liver DiseaseUndergoing an Elective Procedure

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: NCT01972529
Recruitment Status : Completed
First Posted : October 30, 2013
Results First Posted : February 27, 2018
Last Update Posted : February 27, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Thrombocytopenia Associated With Liver Disease
Interventions Drug: avatrombopag (lower baseline platelet count)
Drug: placebo (lower baseline platelet count)
Drug: avatrombopag (higher baseline platelet count)
Drug: placebo (higher baseline platelet count)
Enrollment 231
Recruitment Details  
Pre-assignment Details A total of 370 participants signed informed consent. Of these 370 participants, 139 were screening failures and 231 were randomized into the study. Of the 139 screening failures, 120 did not meet the inclusion/exclusion criteria and the other 19 participants failed due to adverse events, lost to follow-up and withdrawal of consent.
Arm/Group Title 60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Hide Arm/Group Description Participants with a baseline platelet count of less than 40 x 10^9/liters (L) took three 20 milligrams (mg) (60 mg total) matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the elective procedure. Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Period Title: Overall Study
Started 48 90 34 59
Completed 46 85 32 55
Not Completed 2 5 2 4
Reason Not Completed
Adverse Event             0             1             0             0
Lost to Follow-up             1             0             0             0
Participant Choice             0             1             0             0
Withdrawl of Consent             1             2             0             1
Not Specified             0             0             0             2
Not treated             0             1             2             1
Arm/Group Title 60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count) Total
Hide Arm/Group Description Participants with a baseline platelet count of less than 40 x 10^9/liters (L) took three 20 milligrams (mg) matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Total of all reporting groups
Overall Number of Baseline Participants 48 90 34 59 231
Hide Baseline Analysis Population Description
Full analysis set was defined as the group of all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 90 participants 34 participants 59 participants 231 participants
55.1  (11.02) 55.6  (9.12) 57.8  (11.05) 57.5  (10.06) 56.3  (10.06)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 90 participants 34 participants 59 participants 231 participants
Female
16
  33.3%
25
  27.8%
10
  29.4%
22
  37.3%
73
  31.6%
Male
32
  66.7%
65
  72.2%
24
  70.6%
37
  62.7%
158
  68.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 90 participants 34 participants 59 participants 231 participants
Hispanic or Latino
10
  20.8%
10
  11.1%
3
   8.8%
7
  11.9%
30
  13.0%
Not Hispanic or Latino
37
  77.1%
77
  85.6%
31
  91.2%
51
  86.4%
196
  84.8%
Unknown or Not Reported
1
   2.1%
3
   3.3%
0
   0.0%
1
   1.7%
5
   2.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 90 participants 34 participants 59 participants 231 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
18
  37.5%
32
  35.6%
15
  44.1%
24
  40.7%
89
  38.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
3
   3.3%
0
   0.0%
2
   3.4%
5
   2.2%
White
28
  58.3%
50
  55.6%
19
  55.9%
31
  52.5%
128
  55.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   4.2%
5
   5.6%
0
   0.0%
2
   3.4%
9
   3.9%
1.Primary Outcome
Title Percentage of Participants Who Did Not Require a Platelet Transfusion or Any Rescue Procedure for Bleeding After Randomization Following a Scheduled Procedure
Hide Description Responders were defined as participants who did not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure. Participants with missing information due to early withdrawal or other reasons were conservatively considered as having received a transfusion in the analysis, (i.e. a Non-responder).
Time Frame Baseline (Visit 2) up to 7 days following a scheduled procedure
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis Set (FAS) was defined as the group of all randomized participants.
Arm/Group Title 60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Hide Arm/Group Description:
Participants with a baseline platelet count of less than 40 x 10^9/liters (L ) took three 20 milligrams (mg) matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Overall Number of Participants Analyzed 48 90 34 59
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
22.9
(11.0 to 34.8)
65.6
(55.7 to 75.4)
38.2
(21.9 to 54.6)
88.1
(79.9 to 96.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 60 mg Placebo (Lower Baseline Platelet Count), 60 mg Avatrombopag, (Lower Baseline Platelet Count)
Comments The null hypothesis was that the proportion of participants not requiring a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure was the same between the 60 mg avatrombopag and matched placebo treatment groups.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by the risk of bleeding associated with the elective procedure within each baseline platelet count cohort.
Method of Estimation Estimation Parameter Difference of proportion vs placebo
Estimated Value 42.6
Confidence Interval (2-Sided) 95%
27.2 to 58.1
Estimation Comments Difference of proportion versus (vs) placebo = proportion of Responders for avatrombopag – proportion of Responders for placebo; 95% CI is calculated based on normal approximation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 40 mg Placebo (Higher Baseline Platelet Count), 40 mg Avatrombopag (Higher Baseline Platelet Count)
Comments The null hypothesis was that the proportion of participants not requiring a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure was the same between the avatrombopag and placebo treatment groups.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by the risk of bleeding associated with the elective procedure within each baseline platelet count cohort.
Method of Estimation Estimation Parameter Difference of proportion vs placebo
Estimated Value 49.9
Confidence Interval (2-Sided) 95%
31.6 to 68.2
Estimation Comments Difference of proportion vs placebo = proportion of Responders for avatrombopag – proportion of Responders for placebo; 95% CI is calculated based on normal approximation.
2.Secondary Outcome
Title Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on the Scheduled Procedure Day
Hide Description Responders were defined as participants who achieved a platelet count greater than or equal to 50 x 10^9/L on the procedure day. Participants with missing a platelet count on the procedure day were conservatively considered as not achieving a platelet count of 50x10^9/L in the analysis, (i.e. Non-responders).
Time Frame Day 10 to Day 13 (Visit 4)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Hide Arm/Group Description:
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Overall Number of Participants Analyzed 48 90 34 59
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
4.2
(0.0 to 9.8)
68.9
(59.3 to 78.5)
20.6
(7.0 to 34.2)
88.1
(79.9 to 96.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 60 mg Placebo (Lower Baseline Platelet Count), 60 mg Avatrombopag, (Lower Baseline Platelet Count)
Comments The null hypothesis was that the proportion of participants not requiring a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure was the same between the avatrombopag and placebo treatment groups
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments P-value is stratified by the risk of bleeding associated with the elective procedure within each baseline platelet count cohort.
Method of Estimation Estimation Parameter Difference of proportion vs placebo
Estimated Value 64.7
Confidence Interval (2-Sided) 95%
53.6 to 75.8
Estimation Comments Difference of proportion vs placebo = proportion of responders for avatrombopag – proportion of responders for placebo; 95% CI is calculated based on normal approximation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 40 mg Placebo (Higher Baseline Platelet Count), 40 mg Avatrombopag (Higher Baseline Platelet Count)
Comments The null hypothesis was that the proportion of participants not requiring a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure was the same between the avatrombopag and placebo treatment groups
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments P-value is stratified by the risk of bleeding associated with the elective procedure within each baseline platelet count cohort.
Method of Estimation Estimation Parameter Difference of percentage vs placebo
Estimated Value 67.5
Confidence Interval (2-Sided) 95%
51.6 to 83.4
Estimation Comments Difference of proportion vs placebo = proportion of responders for avatrombopag – proportion of responders for placebo; 95% CI is calculated based on normal approximation.
3.Secondary Outcome
Title Change From Baseline in Platelet Count on the Scheduled Procedure Day
Hide Description Last observation carried forward was used for participants with a missing platelet count on the scheduled procedure day. Platelet count was measured preprocedure and before any platelet transfusion.
Time Frame Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Hide Arm/Group Description:
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Overall Number of Participants Analyzed 48 88 32 58
Mean (Standard Deviation)
Unit of Measure: Platelet count x 10^9/per liter
0.8  (6.36) 32.0  (25.53) 1.0  (9.30) 37.1  (27.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 60 mg Placebo (Lower Baseline Platelet Count), 60 mg Avatrombopag, (Lower Baseline Platelet Count)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments P-value is based on Wilcoxon rank sum test for each avatrombopag treatment group vs placebo within each baseline platelet count cohort.
Method of Estimation Estimation Parameter Difference in change of platelet count
Estimated Value 27.5
Confidence Interval (2-Sided) 95%
22.5 to 32.5
Estimation Comments Difference in change from baseline of platelet count for avatrombopag vs placebo within each baseline platelet count cohort is based on Hodges-Lehmann estimation; 95% confidence interval is the asymptotic (Moses) CI.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 40 mg Placebo (Higher Baseline Platelet Count), 40 mg Avatrombopag (Higher Baseline Platelet Count)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments P-value is based on Wilcoxon rank sum test for each avatrombopag treatment group vs placebo within each baseline platelet count cohort.
Method of Estimation Estimation Parameter Difference in change of platelet count
Estimated Value 33.0
Confidence Interval (2-Sided) 95%
25.5 to 41.5
Estimation Comments Difference in change from baseline of platelet count for avatrombopag vs placebo within each baseline platelet count cohort is based on Hodges-Lehmann estimation; 95% confidence interval is the asymptotic (Moses) CI.
4.Other Pre-specified Outcome
Title Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After a Scheduled Procedure
Hide Description The severity of bleeding events was assessed by the investigator (or appropriately delegated study site personnel) using the WHO bleeding scale. The WHO bleeding scale is a clinical investigator-assessed five-point scale with Grade 0 = No bleeding, Grade 1 = Petechial bleeding, Grade 2 = Mild blood loss (clinically significant), Grade 3 = Gross blood loss (requires transfusion (severe)), and Grade 4 = Debilitating blood loss, retinal or cerebral associated with fatality. Participants with missing information are considered as having a WHO bleeding score greater than or equal to 2 in the analysis.
Time Frame Baseline (Visit 2) up to 7 days post scheduled procedure
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Hide Arm/Group Description:
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Overall Number of Participants Analyzed 48 90 34 59
Measure Type: Number
Unit of Measure: Percentage of participants
6.3 5.6 2.9 0
5.Other Pre-specified Outcome
Title Number of Participants Experiencing an Adverse Event
Hide Description Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious adverse events, including platelet transfusion-related complications; routine laboratory evaluation for hematology, serum chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); the performance of physical examinations; and Doppler sonography. AE severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death related to the AE. All AEs graded as 4 or 5 were considered to be serious. Treatment-emergent adverse events (TEAEs) were defined as an AE that started on or after the date of first dose of study drug, up to 30 days after the last dose of study drug. Treatment-related AEs were considered by the investigator to be possibly or probably related to study drug.
Time Frame From date of first dose of study drug up to 30 days after the last dose of study drug, up to approximately 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
Arm/Group Title 60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Hide Arm/Group Description:
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
Overall Number of Participants Analyzed 48 89 32 58
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
31
  64.6%
53
  59.6%
18
  56.3%
31
  53.4%
Treatment-related TEAEs
7
  14.6%
12
  13.5%
2
   6.3%
4
   6.9%
Serious TEAEs
11
  22.9%
10
  11.2%
1
   3.1%
8
  13.8%
TEAEs leading to study drug dose adjustment
0
   0.0%
2
   2.2%
0
   0.0%
0
   0.0%
TEAEs leading to study drug withdrawal
0
   0.0%
2
   2.2%
0
   0.0%
0
   0.0%
TEAEs leading to study drug dose reduction
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame From date of administration of first dose up to 30 days after the last dose, up to approximately 3 years
Adverse Event Reporting Description Treatment-emergent adverse events and all serious adverse events were reported. Adverse events were graded using Common Terminology Criteria for Adverse Event version 4. Safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 post dose safety assessment. This set was analyzed “as treated".
 
Arm/Group Title 60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Hide Arm/Group Description Participants with a baseline platelet count of less than 40 x 10^9/liters (L) took three 20 milligrams (mg) matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Participants with a baseline platelet count of less than 40 x 10^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg matching placebo tablets orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure. Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal during the Treatment Period on Days 1 through 5, and 5 to 8 days prior to the scheduled procedure.
All-Cause Mortality
60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/48 (0.00%)   0/89 (0.00%)   0/32 (0.00%)   2/58 (3.45%) 
Show Serious Adverse Events Hide Serious Adverse Events
60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/48 (22.92%)   10/89 (11.24%)   1/32 (3.13%)   8/58 (13.79%) 
Blood and lymphatic system disorders         
Anaemia  1  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Splenomeglay  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Stress polycythaemia  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Haemorrhagic anaemia  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Splenic haemorrhage  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Splenic infarction  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Ear and labyrinth disorders         
Vertigo  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Abdominal Pain Upper  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Ascites  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Diarrhoea  2  0/48 (0.00%)  1/89 (1.12%)  1/32 (3.13%)  0/58 (0.00%) 
Upper gastrointestinal haemorrhage  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  1/58 (1.72%) 
Oesophageal varices haemorrhage  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Gastrointestinal haemorrhage  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Haematemesis  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
General disorders         
Generalised oedema  2  1/48 (2.08%)  0/89 (0.00%)  0/32 (0.00%)  0/58 (0.00%) 
Pyrexia  2  1/48 (2.08%)  0/89 (0.00%)  1/32 (3.13%)  0/58 (0.00%) 
Multiple Organ dysfunction syndrome  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Hepatobiliary disorders         
Chronic hepatic failure  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Infections and infestations         
Cellulitis  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Clostridium difficile infection  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Pneumonia  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Sepsis  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Urinary tract infection  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Injury, poisoning and procedural complications         
Anaphylactic transfusion reaction  2  1/48 (2.08%)  0/89 (0.00%)  0/32 (0.00%)  0/58 (0.00%) 
Post procedural haemorrhage  2  1/48 (2.08%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Procedural haemorrhage  2  1/48 (2.08%)  0/89 (0.00%)  0/32 (0.00%)  0/58 (0.00%) 
Procedural pain  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Transfusion reaction  2  3/48 (6.25%)  0/89 (0.00%)  0/32 (0.00%)  0/58 (0.00%) 
Investigations         
Clostridium test positive  2  1/48 (2.08%)  0/89 (0.00%)  0/32 (0.00%)  0/58 (0.00%) 
Platelet count decreased  2  1/48 (2.08%)  0/89 (0.00%)  0/32 (0.00%)  0/58 (0.00%) 
Metabolism and nutrition disorders         
Hyperkalaemia  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Hyponatraemia  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  1/58 (1.72%) 
Musculoskeletal and connective tissue disorders         
Muscle spasms  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Myalgia  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Nervous system disorders         
Coma hepatic  2  0/48 (0.00%)  0/89 (0.00%)  0/32 (0.00%)  1/58 (1.72%) 
Hepatic encephalopathy  2  1/48 (2.08%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Syncope  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Azotaemia  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Epistaxis  2  1/48 (2.08%)  0/89 (0.00%)  0/32 (0.00%)  0/58 (0.00%) 
Vascular disorders         
Hypotension  2  0/48 (0.00%)  1/89 (1.12%)  0/32 (0.00%)  0/58 (0.00%) 
1
Term from vocabulary, MeDRA 19.1
2
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
60 mg Placebo (Lower Baseline Platelet Count) 60 mg Avatrombopag, (Lower Baseline Platelet Count) 40 mg Placebo (Higher Baseline Platelet Count) 40 mg Avatrombopag (Higher Baseline Platelet Count)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/48 (27.08%)   28/89 (31.46%)   9/32 (28.13%)   16/58 (27.59%) 
Gastrointestinal disorders         
Abdominal pain  1  3/48 (6.25%)  8/89 (8.99%)  3/32 (9.38%)  5/58 (8.62%) 
Dyspepsia  2  2/48 (4.17%)  0/89 (0.00%)  2/32 (6.25%)  0/58 (0.00%) 
Nausea  2  2/48 (4.17%)  4/89 (4.49%)  2/32 (6.25%)  5/58 (8.62%) 
General disorders         
Fatigue  2  1/48 (2.08%)  6/89 (6.74%)  1/32 (3.13%)  1/58 (1.72%) 
Oedema peripheral  2  2/48 (4.17%)  3/89 (3.37%)  1/32 (3.13%)  3/58 (5.17%) 
Pyrexia  2  5/48 (10.42%)  7/89 (7.87%)  1/32 (3.13%)  5/58 (8.62%) 
Infections and infestations         
Gastroenteritis  2  0/48 (0.00%)  0/89 (0.00%)  2/32 (6.25%)  0/58 (0.00%) 
Injury, poisoning and procedural complications         
Procedural pain  2  0/48 (0.00%)  6/89 (6.74%)  0/32 (0.00%)  0/58 (0.00%) 
Nervous system disorders         
Headache  2  3/48 (6.25%)  5/89 (5.62%)  2/32 (6.25%)  6/58 (10.34%) 
1
Term from vocabulary, MeDRA 19.1
2
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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: Eisai Medical Services
Organization: Eisai Inc
Phone: 1-888-274-2378
EMail: esi_medinfo@eisai.com
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01972529     History of Changes
Other Study ID Numbers: E5501-G000-310
2013-000965-34 ( EudraCT Number )
First Submitted: October 24, 2013
First Posted: October 30, 2013
Results First Submitted: December 27, 2017
Results First Posted: February 27, 2018
Last Update Posted: February 27, 2018