title: Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure.
abstract: OBJECTIVE
  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 ⩽58×10(9)/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100mg 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 20mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ⩾20×10(9)/L from baseline and >50×10(9)/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.
authors.affiliation: University of California San Francisco, San Francisco, CA, United States. Electronic address: norah.terrault@ucsf.edu.
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
authors.affiliation: Southern California Liver Centers, Coronado, CA, United States.
authors.forename: Tarek
authors.initials: T
authors.lastname: Hassanein
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Howell
authors.affiliation: Tulane University School of Medicine, New Orleans, LA, United States.
authors.forename: Shobha
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
authors.forename: John
authors.initials: J
authors.lastname: Lake
authors.affiliation: University of Southern California, Los Angeles, CA, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Sher
authors.affiliation: Mayo Clinic Hospital, Phoenix, AZ, United States.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vargas
authors.affiliation: Eisai Corporation of North America, Woodcliff Lake, NJ, United States.
authors.forename: Joe
authors.initials: J
authors.lastname: McIntosh
authors.affiliation: Eisai Corporation of North America, Woodcliff Lake, NJ, United States.
authors.forename: Shande
authors.initials: S
authors.lastname: Tang
authors.affiliation: Eisai Ltd, Hatfield, UK.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Jenkins
mesh_terms: D001792:Blood Platelets / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D005221:Fatigue / Q000453:epidemiology; D005260:Female; D006261:Headache / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000453:epidemiology; D010976:Platelet Count; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D012307:Risk Factors; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000209:etiology*
chemical_list: D053628:Receptors, Thrombopoietin; D013844:Thiazoles; D013876:Thiophenes; C533238:avatrombopag
keywords: Avatrombopag; Chronic liver disease; Cirrhosis; Elective procedure; Platelet; Thrombocytopenia; Thrombopoietin receptor agonist