Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure

Norah A. Terrault, Tarek Hassanein, Charles D. Howell, Shobha Joshi, John Lake, Linda Sher, Hugo Vargas, Joe McIntosh, Shande Tang, Tim M. Jenkins

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background & Aims This is a phase II multicentre study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis. Methods Adults with cirrhosis and platelet counts ≥10 to ≤58 × 109/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100 mg loading dose followed by 20, 40, or 80 mg/day on days 2-7) of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2 different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or 20 mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ≥20 × 109/L from baseline and >50 × 109/L at least once during days 4-8. Results A total of 130 patients were randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16, cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0% of treated patients in cohort A and 47.6% in cohort B compared to 6.3% and 9.5% of controls; a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p <0.01), except for the 100/40 mg group in cohort A (p = 0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avatrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up. Conclusions In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.

Original languageEnglish (US)
Pages (from-to)1253-1259
Number of pages7
JournalJournal of hepatology
Issue number6
StatePublished - Dec 1 2014


  • Avatrombopag
  • Chronic liver disease
  • Cirrhosis
  • Elective procedure
  • Platelet
  • Thrombocytopenia
  • Thrombopoietin receptor agonist

ASJC Scopus subject areas

  • Hepatology


Dive into the research topics of 'Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure'. Together they form a unique fingerprint.

Cite this