@entity7142 versus @entity18111 for primary treatment of XXXX caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.

@entity1 @entity5 @entity10998 @entity344 @entity281 @entity735 @entity74 @entity3 @entity18111 @entity7142
BACKGROUND: @entity7142 is a novel @entity10998 with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of @entity7142 versus @entity18111 in @entity1 with @entity3 . METHODS: This was a phase 3, double-blind, global multicentre, comparative-group study. @entity1 with suspected @entity3 were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active @entity5 at baseline, to receive @entity7142 372 mg (prodrug; equivalent to 200 mg @entity7142 ; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or @entity18111 (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in @entity1 who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in @entity1 who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. FINDINGS: 527 adult @entity1 were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with @entity7142 (48 @entity1 ) and 20% with @entity18111 (52 @entity1 ), with an adjusted treatment difference of -1  0% (95% CI -7  8 to 5  7). Because the upper bound of the 95% CI (5  7%) did not exceed 10%, non-inferiority was shown. Most @entity1 (247 [96%] receiving @entity7142 and 255 [98%] receiving @entity18111 ) had treatment-emergent adverse events (p=0  122); the most common were @entity344 (174 [68%] vs 180 [69%]) and @entity281 (152 [59%] vs 158 [61%]). Proportions of @entity1 with treatment-emergent adverse events by system organ class were similar overall. However, @entity7142 -treated @entity1 had a lower frequency of @entity74 (23 [9%] vs 42 [16%]; p=0  016), @entity735 (39 [15%] vs 69 [27%]; p=0  002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0  037). Drug-related adverse events were reported in 109 (42%) @entity1 receiving @entity7142 and 155 (60%) receiving @entity18111 (p<0  001). INTERPRETATION: @entity7142 was non-inferior to @entity18111 for the primary treatment of suspected @entity3 . @entity7142 was well tolerated compared with @entity18111 , with fewer study-drug-related adverse events. Our results support the use of @entity7142 for the primary treatment of @entity1 with @entity3 . FUNDING: Astellas Pharma Global Development, Basilea Pharmaceutica International.
