Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing an Elective Procedure

Phase 3

Completed

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)

Brief Summary: 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).

Detailed Description: This study will consist of 3 phases: Prerandomization, Randomization, and a Follow-up Phase. The Prerandomization Phase includes one Screening Visit that will take place from Day -14 through Day -1; the Randomization Phase includes the Baseline Period, Treatment Period, and Procedure Day Period (5 to 8 days after last dose of study drug \[Study Day 10 to 13\]). The Follow-up Phase comprises 2 visits: 7 days post Procedure Day and 30 days after receiving the last dose of study drug. Permitted procedures include: Paracentesis; Thoracentesis; Gastrointestinal endoscopy with or without plans for biopsy, colonoscopy, polypectomy, or variceal banding; Liver biopsy; Bronchoscopy with or without plans for biopsy; Ethanol ablation therapy or chemoembolization for HCC; Vascular catheterization (including right side procedures in participants with pulmonary hypertension); Transjugular intrahepatic portosystemic shunt; Dental procedures; Renal biopsy; Biliary interventions; Nephrostomy tube placement; Radiofrequency ablation; and Laparoscopic interventions.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Group A (avatrombopag, lower baseline platelet count)	avatrombopag (lower baseline platelet count)	60 mg avatrombopag (3 x 20 mg tablets) once daily on Days 1 through 5
Group B (placebo, lower baseline platelet count)	placebo (lower baseline platelet count)	placebo (3 x 20 mg matching placebo tablets) once daily on Days 1 through 5
Group C (avatrombopag, higher baseline platelet count)	avatrombopag (higher baseline platelet count)	40 mg avatrombopag (2 x 20 mg tablets) once daily on Days 1 through 5
Group D (placebo, higher baseline platelet count)	placebo (higher baseline platelet count)	placebo (2 x 20 mg matching placebo tablets) once daily on Days 1 through 5

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Did Not Require a Platelet Transfusion After Randomization and up to 7 Days Following a Scheduled Procedure	Randomization (Visit 2), up to 7 Days following a scheduled procedure	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).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day	Day 10 to Day 13 (Visit 4)	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 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).
Change From Baseline in Platelet Counts on Scheduled Procedure Day	Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4)	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.