NCT04915287

Efficacy of Avatrombopag in Thrombocytopenic Patients With Chronic Liver Disease Undergoing an Elective Procedure

Efficacy of Avatrombopag in Thrombocytopenic Patients With Chronic Liver Disease Undergoing an Elective Procedure: A Prospective Non-randomized Controlled Trial

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 476 (estimated)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this study, investigators aimed to evaluate the efficacy of Avatrombopag in thrombocytopenic patients with chronic liver disease undergoing an elective invasive procedure through a prospective, non-randomized controlled, multicenter clinical trial. The patients were non-randomly assigned to the Avatrombopag group (119 patients) and the conventional treatment group (357 patients). The primary endpoint was the proportion of patients not requiring prophylactic platelet transfusion or rescue therapy due to bleeding from grouping up to 10 days post-procedure. Second endpoints included the proportion of patients achieving a platelet count of ≥50x10\^9/L and the mean change in platelet count from baseline at the time before the procedure, the proportion of patients requiring platelet transfusion and the mean platelet transfusion units per capita, the incidence of bleeding events (WHO≥2 and requiring rescue therapy), the imaging evaluations of bleeding events, the incidence of adverse events, the changes in life quality between two groups before and after treatment, and the pharmacoeconomic index of two groups. Note: According to the results of interim statistical analysis (200-300 cases), it is up to the sponsor to decide whether to terminate the study in advance or increase the number of included cases at a later stage.

Detailed description

Thrombocytopenia is a common complication of chronic liver disease (CLD), which severity increases with the aggravation of CLD. TPO, the primary physiological regulator of platelet production, is mainly produced by the liver. With the progressive liver injury in patients with CLD, TPO production decreases, resulting in the reduction of platelet production and thrombocytopenia, which cause the significantly increased risk of bleeding during the invasive procedure in these patients and pose a severe challenge to clinical management. Platelet transfusion is a standard clinical treatment for CLD-related thrombocytopenia. Whether prophylactic platelet transfusion is needed before elective invasive procedure depends on the level of platelet count and the judgment of medical staff on the risk of bleeding in those procedures. Clinically, without effective preventive treatment in severe thrombocytopenia (PLT\< 50×10\^9/L), the risk of bleeding in related procedures is high, the hospitalization is prolonged after bleeding, and other post-procedure complications may occur. However, repeated prophylactic platelet transfusion may lead to ineffective platelet transfusion. ADAPT-1 and ADAPT-2 were identical design randomized, double-blinded, placebo-controlled, international multicenter phase III clinical trials. They confirmed that 1. Avatrombopag could significantly increase the platelet count in patients with chronic liver disease with severe thrombocytopenia (PLT\<50×10\^9/L), thus reducing the proportion of platelet transfusion or rescue due to bleeding in adult patients with chronic liver disease-associated thrombocytopenia undergoing elective invasive procedures; 2. In terms of safety, the incidence of adverse events in the Avatrombopag group was comparable to that in the placebo group. At present, Avatrombopag has been successively approved in Europe, the United States, and China for adult patients with chronic liver disease-associated thrombocytopenia undergoing elective invasive procedures. Avatrombopag is effective and safe in raising platelet count in patients with chronic liver disease. In addition, it has the characteristics of no risk of neutralizing antibody generation from small molecules and convenient oral administration. The purpose of this study was to observe the clinical benefit of Avatrombopag to raise platelet count in adult patients with chronic liver disease-associated thrombocytopenia who received elective high-risk invasive procedures and to validate the efficacy and safety of Avatrombopag further in Chinese population with different spectrum of etiology in chronic liver disease. Note: According to the results of interim statistical analysis (200-300 cases), it is up to the sponsor to decide whether to terminate the study in advance or increase the number of included cases at a later stage.

Conditions

• Thrombocytopenia; Drugs
• Chronic Liver Disease

Interventions

Type	Name	Description
DRUG	Avatrombopag maleate	1. Mean baseline platelet count 40 to less than 50 × 10\^9/L: 40mg Avatrombopag QD × 5 days from 10-13 days pre-procedure 2. Mean baseline platelet count less than 40 × 10\^9/L: 60mg Avatrombopag QD × 5 days from 10-13 days pre-procedure
BIOLOGICAL	Platelet transfusion	Mean baseline platelet count less than 50 × 10\^9/L pre-procedure: platelet transfusion if needed
DRUG	Medicine	Mean baseline platelet count less than 50 × 10\^9/L pre-procedure: rhuTPO, rhIL-11, Romiplostim, Eltrombopag, or Lusutrombopag, etc.

Timeline

• Start date: 2021-06-06
• Primary completion: 2023-06-30
• Completion: 2023-07-31
• First posted: 2021-06-07
• Last updated: 2022-11-15

Locations

1 site across 1 country: China

Regulatory

• FDA-regulated drug study