This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag to treat adults with thrombocytopenia associated with liver disease. The study will evaluate avatrombopag in the treatment of thrombocytopenia associated with liver disease prior to an elective procedure to reduce the need for platelet transfusions or any rescue procedure for bleeding due to procedural and post-procedural bleeding complications. Participants will be enrolled into 2 cohorts according to mean baseline platelet count and, within each baseline platelet count cohort will be further stratified by risk of bleeding associated with the elective procedure (low, moderate, or high) and hepatocellular carcinoma (HCC) status (Yes or No).
Name: avatrombopag (lower baseline platelet count)
Name: placebo (lower baseline platelet count)
Name: avatrombopag (higher baseline platelet count)
Name: placebo (higher baseline platelet count)
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).
Measure: Percentage of Participants Who Did Not Require a Platelet Transfusion or Any Rescue Procedure for Bleeding After Randomization Following a Scheduled Procedure Time: Baseline (Visit 2) up to 7 days following a scheduled procedureDescription: 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).
Measure: Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on the Scheduled Procedure Day Time: Day 10 to Day 13 (Visit 4)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.
Measure: Change From Baseline in Platelet Count on the Scheduled Procedure Day Time: Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4)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.
Measure: Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After a Scheduled Procedure Time: Baseline (Visit 2) up to 7 days post scheduled procedureDescription: 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.
Measure: Number of Participants Experiencing an Adverse Event Time: From date of first dose of study drug up to 30 days after the last dose of study drug, up to approximately 3 yearsAllocation: Randomized
Parallel Assignment
There is one SNP
Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.) 18. Participants with a history of significant cardiovascular disease (eg, congestive heart failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events [eg, atrial fibrillation], coronary artery stent placement, angioplasty, and coronary artery bypass grafting) 19. --- G20210A ---