Doptelet reduces procedural bleeding risk in patients with chronic liver disease

Results of two phase 3 trials showed that Doptelet significantly reduced the need for platelet transfusions or rescue procedures for bleeding compared with placebo in patients with thrombocytopenia and chronic liver disease who underwent a scheduled procedure.

“Thrombocytopenia is common in patients with chronic liver disease (CLD), affecting up to 84% of patients, and worsens with the degree of cirrhosis,” Norah Terrault, MD, MPH, from the University of California, San Francisco, and colleagues wrote. “Avatrombopag has been developed as an alternative to platelet transfusions for patients with thrombocytopenia and CLD scheduled for a procedure to minimize bleeding and other safety risks and improve clinical management.”

Doptelet (avatrombopag, Dova/AkaRx) recently received FDA approval for treating patients with thrombocytopenia and chronic liver disease to reduce bleeding risk. It is an oral, small molecule thrombopoietin receptor agonist developed to provide a predictable increase in platelet counts as an alternative to platelet transfusions.
In two identically designed phase 3 trials — ADAPT-1 and ADAPT-2 — Terrault and colleagues randomly assigned patients to receive daily doses of avatrombopag or placebo for 5 days.

Significantly more treated patients with a low baseline platelet count did not require a platelet transfusion or rescue procedure for bleeding in both the ADAPT-1 trial (65.6% vs. 22.9%; P < .0001) and the ADAPT-2 trial (68.6% vs. 34.9%; P < .0006) compared with placebo. Similarly, more treated patients with a high baseline platelet count did not require transfusion or rescue procedure in both ADAPT-1 (88.1% vs. 38.2%; P < .0001) and ADAPT-2 (87.9% vs. 33.3%; P < .0001).

Subgroup analysis confirmed the efficacy of avatrombopag compared with placebo in patients undergoing procedures with low (84% vs. 40.7%), moderate (75.6% vs. 31%) and high (70.5% vs. 20.7%) bleeding risks, as well as its superiority to placebo regardless of age, sex, race, region, MELD score, Child-Turcotte Pugh class or disease etiology.
Both patients with low and high baseline platelet counts achieved the target platelet count of 50 × 109/L significantly more often than placebo in both trials (P < .0001).

Terrault and colleagues observed similar safety profiles between avatrombopag and placebo, including the overall incidence of serious adverse events, except for two patients who experienced both gastrointestinal hemorrhage and hyponatremia.

“By design, the magnitude and duration of the platelet-count increase with avatrombopag in the ADAPT trials was predictable and of short duration, making it ideal for prophylactic use for scheduled procedures,” the researchers wrote. – by Talitha Bennett

Disclosure: Terrault reports she received research grants from AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead and Merck. Please see the full study for the other researchers’ relevant financial disclosures.