Background
Phase III, double-blind, placebo-controlled RCT. 215 patients with CLD and thrombocytopenia (platelet count <50 × 10⁹/L) scheduled for elective invasive procedures. Enrolled in 9 countries. Patients with prior history of PVT within 12 months excluded. CLD etiologies included viral hepatitis B/C and alcohol-related cirrhosis.
Interventions and follow up
Arm A: Lusutrombopag 3 mg/day orally for up to 7 days (start ≥9 days before procedure)
Arm B: Placebo
Primary endpoint: Proportion not requiring platelet transfusion pre-procedure or rescue transfusio
mFollow up: Day 35 post-procedure
Arm B: Placebo
Primary endpoint: Proportion not requiring platelet transfusion pre-procedure or rescue transfusio
mFollow up: Day 35 post-procedure
Results
Primary endpoint (transfusion avoidance): 64.8% vs 29.0%, P<.0001
Platelet count increase ≥50 × 10⁹/L on procedure day: 64.8% vs 13.1%
Portal vein thrombosis: 0 events in lusutrombopag arm
Platelet count increase ≥50 × 10⁹/L on procedure day: 64.8% vs 13.1%
Portal vein thrombosis: 0 events in lusutrombopag arm
Adverse events
Main adverse events: Grade ≥3 AEs: 13.2% vs 7.5%. No portal vein thrombosis detected by imaging follow-up. Headache and nasopharyngitis most common. No hepatotoxicity. Overall safety profile similar to placebo.
Conclusions
Lusutrombopag 3 mg × ≤7 days significantly reduced platelet transfusion requirement before invasive procedures in CLD patients, with no portal vein thrombosis signal. It was FDA approved in 2018 for this indication, as the first oral TPO receptor agonist approved for CLD-related thrombocytopenia.
Key Limitations
Key Limitations: Relatively modest platelet increases in a proportion of patients — some still required transfusion despite treatment. Fixed 7-day maximum dosing window may not accommodate all procedure scheduling. The trial was conducted predominantly in Asian countries (Japan, Korea), and the applicability to Western CLD populations (higher NASH/alcohol proportion) requires consideration. Direct comparisons to avatrombopag have not been performed in an RCT.
Clinical Context
FDA approved in July 2018 for thrombocytopenia in adults with CLD scheduled for a procedure — first in class for this indication. Together with avatrombopag (2019), it has displaced platelet transfusions as the preferred management pre-procedure for CLD thrombocytopenia in guidelines. Unlike eltrombopag (ELEVATE trial), neither lusutrombopag nor avatrombopag showed a PVT signal. Board pearl: eltrombopag = PVT risk in CLD → NOT approved; lusutrombopag + avatrombopag = safe → both approved.
References