passages: 1905
passages: document
passages: Eltrombopag for management of chronic immune thrombocytopenia ( RAISE ) : a 6-month , randomised , phase 3 study . BACKGROUND Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia . We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period . METHODS We undertook a phase 3 , double-blind , placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months ' duration who had baseline platelet counts lower than 30,000 per μL . Patients were randomly allocated ( in a 2:1 ratio ) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months . Randomisation was done centrally with a computer-generated randomisation schedule and was stratified by baseline platelet count ( ≤ 15,000 per μL ) , use of treatment for immune thrombocytopenia , and splenectomy status . Patients , investigators , and those assessing data were masked to allocation . Dose modifications were made on the basis of platelet response . Patients were assessed for response to treatment ( defined as a platelet count of 50,000-400,000 per μL ) weekly during the first 6 weeks and at least once every 4 weeks thereafter ; the primary endpoint was the odds of response to eltrombopag versus placebo . Analysis was by intention to treat . This study is registered at ClinicalTrials.gov , number NCT00370331 . FINDINGS Between Nov 22 , 2006 , and July 31 , 2007 , 197 patients were randomly allocated to treatment groups and were included in the intention-to-treat analysis ( 135 eltrombopag , 62 placebo ) . 106 ( 79 % ) patients in the eltrombopag group responded to treatment at least once during the study , compared with 17 ( 28 % ) patients in the placebo group . The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period ( odds ratio 8·2 , 99 % CI 3·59-18·73 ; p < 0·0001 ) . 37 ( 59 % ) patients receiving eltrombopag reduced concomitant treatment versus ten ( 32 % ) patients receiving placebo ( p=0·016 ) . 24 ( 18 % ) patients receiving eltrombopag needed rescue treatment compared with 25 ( 40 % ) patients receiving placebo ( p=0·001 ) . Three ( 2 % ) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo . Nine ( 7 % ) eltrombopag-treated patients and two ( 3 % ) in the placebo group had mild increases in alanine aminotransferase concentration , and five ( 4 % ) eltrombopag-treated patients ( vs none allocated to placebo ) had increases in total bilirubin . Four ( 7 % ) patients taking placebo had serious bleeding events , compared with one ( < 1 % ) patient treated with eltrombopag . INTERPRETATION Eltrombopag is effective for management of chronic immune thrombocytopenia , and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment . These benefits should be balanced with the potential risks associated with eltrombopag treatment . FUNDING GlaxoSmithKline .
entities: 1906
entities: Intervention_Pharmacological
entities: Eltrombopag
entities: 1907
entities: Intervention_Pharmacological
entities: Eltrombopag
entities: 1908
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1909
entities: Intervention_Control
entities: placebo
entities: 1910
entities: Intervention_Control
entities: placebo-controlled
entities: 1911
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1912
entities: Intervention_Control
entities: placebo
entities: 1913
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1914
entities: Intervention_Control
entities: placebo
entities: 1915
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1916
entities: Intervention_Control
entities: placebo
entities: 1917
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1918
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1919
entities: Intervention_Control
entities: placebo
entities: 1920
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1921
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1922
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1923
entities: Intervention_Pharmacological
entities: eltrombopag-treated
entities: 1924
entities: Intervention_Pharmacological
entities: eltrombopag-treated
entities: 1925
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1926
entities: Intervention_Pharmacological
entities: Eltrombopag
entities: 1927
entities: Intervention_Pharmacological
entities: eltrombopag
entities: 1928
entities: Outcome_Physical
entities: response
entities: 1929
entities: Outcome_Physical
entities: response to treatment
entities: 1930
entities: Outcome_Physical
entities: platelet count
entities: 1931
entities: Outcome_Physical
entities: responded to treatment
entities: 1932
entities: Outcome_Adverse-effects
entities: thromboembolic
entities: 1933
entities: Outcome_Adverse-effects
entities: serious bleeding
entities: 1934
entities: Participant_Condition
entities: chronic immune thrombocytopenia
entities: 1935
entities: Participant_Condition
entities: patients with chronic immune thrombocytopenia
entities: 1936
entities: Participant_Age
entities: adults
entities: 1937
entities: Participant_Condition
entities: previously treated immune thrombocytopenia of more than 6 months ' duration
entities: 1938
entities: Participant_Condition
entities: baseline platelet counts lower than 30,000 per μL
entities: 1939
entities: Participant_Sample-size
entities: 197