Background
ADAPT-1 and ADAPT-2: Two identical Phase III, double-blind, placebo-controlled RCTs run in parallel. Combined N=435 patients with chronic liver disease (CLD) and thrombocytopenia (platelet count <50 × 10⁹/L) scheduled for elective procedures. Enrolled across diverse CLD etiologies including viral hepatitis and alcohol-related cirrhosis. Key distinction from ELEVATE: patients with prior PVT were excluded but history of PVT was not the primary exclusion criterion.
Interventions and follow up
Arm A: Avatrombopag 60 mg/day (if baseline platelets <40 × 10⁹/L) or 40 mg/day (if 40–50 × 10⁹/L) orally × 5 day
Arm B: Placebo × 5 day
Primary endpoint: Proportion achieving platelets ≥50 × 10⁹/L AND no platelet transfusion/rescue procedure
mFollow up: Day 35 post-procedure
Arm B: Placebo × 5 day
Primary endpoint: Proportion achieving platelets ≥50 × 10⁹/L AND no platelet transfusion/rescue procedure
mFollow up: Day 35 post-procedure
Results
Primary endpoint (low-baseline cohort, 60 mg): 65% vs 23% (ADAPT-1), 69% vs 35% (ADAPT-2), P<.001 both
Primary endpoint (high-baseline cohort, 40 mg): 88% vs 38% (ADAPT-1), 88% vs 33% (ADAPT-2), P<.001 both
Portal vein thrombosis: 0 events in either avatrombopag arm
Primary endpoint (high-baseline cohort, 40 mg): 88% vs 38% (ADAPT-1), 88% vs 33% (ADAPT-2), P<.001 both
Portal vein thrombosis: 0 events in either avatrombopag arm
Adverse events
Main adverse events: Grade ≥3 AEs: similar to placebo (~25%). No portal vein thrombosis in avatrombopag arm (0 vs 0). Nausea and abdominal pain most common. Thrombotic events overall similar between arms. No significant liver enzyme elevations attributable to drug.
Conclusions
Avatrombopag significantly increased platelet counts and reduced transfusion need pre-procedure in CLD patients across two replicate RCTs, with no signal of portal vein thrombosis. It was FDA approved in 2019 for this indication, offering a safe alternative to platelet transfusion.
Key Limitations
Key Limitations: Platelet target ≥50 × 10⁹/L is a surrogate — clinical bleeding outcomes were not powered as co-primary. The 5-day fixed dosing schedule may not be flexible for emergent procedures. Low-baseline and high-baseline cohorts used different doses, complicating cross-trial comparisons. Open-label use in clinical practice may differ from the tightly controlled trial setting. Long-term platelet dynamics post-procedure were not assessed.
Clinical Context
FDA approved in May 2019 for thrombocytopenia in adults with CLD scheduled for a procedure. Avatrombopag and lusutrombopag (L-PLUS 2) are both approved; avatrombopag does not require food restriction (unlike eltrombopag). The absence of PVT signal — in contrast to the halted ELEVATE trial with eltrombopag — is the defining clinical feature. Preferred over platelet transfusions due to reduced transfusion-related risks and logistical advantages.
References