title: Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg.
  
  
  METHODS
  In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per muL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per microL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per microL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00102739.
  
  
  RESULTS
  73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts >/=50 000 per microL; odds ratio [OR] 9.61 [95% CI 3.31-27.86]; p<0.0001). Response to eltrombopag compared with placebo was not affected by predefined study stratification variables (baseline platelet counts, concomitant ITP drugs, and splenectomy status) or by the number of previous ITP treatments. Of the 34 patients in the efficacy analysis who increased their dose of eltrombopag, ten (29%) responded. Platelet counts generally returned to baseline values within 2 weeks after the end of treatment. Patients receiving eltrombopag had less bleeding at any time during the study than did those receiving placebo (OR 0.49 [95% CI 0.26-0.89]; p=0.021). The frequency of grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups.
  
  
  CONCLUSIONS
  Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP.
authors.affiliation: Weill-Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.forename: Drew
authors.initials: D
authors.lastname: Provan
authors.forename: Tahir
authors.initials: T
authors.lastname: Shamsi
authors.forename: Gregory
authors.initials: G
authors.lastname: Cheng
authors.forename: Bethan
authors.initials: B
authors.lastname: Psaila
authors.forename: Lidia
authors.initials: L
authors.lastname: Kovaleva
authors.forename: Abdulgabar
authors.initials: A
authors.lastname: Salama
authors.forename: Julian M
authors.initials: JM
authors.lastname: Jenkins
authors.forename: Debasish
authors.initials: D
authors.lastname: Roychowdhury
authors.forename: Bhabita
authors.initials: B
authors.lastname: Mayer
authors.forename: Nicole
authors.initials: N
authors.lastname: Stone
authors.forename: Michael
authors.initials: M
authors.lastname: Arning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; C520809:eltrombopag