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Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With Clostridium difficile Infection.

ABSTRACT: BACKGROUND:Although the incidence of Clostridium difficile infection (CDI) is increasing, available CDI treatment options are limited in terms of sustained response after treatment. This phase 3 trial assessed the efficacy and safety of surotomycin, a novel bactericidal cyclic lipopeptide, versus oral vancomycin in subjects with CDI. METHODS:In this randomized, double-blind, active-controlled, multicenter, international trial, subjects with CDI confirmed by a positive toxin result were randomized to receive surotomycin (250 mg twice daily) or vancomycin (125 mg 4 times daily) orally for 10 days. The primary endpoints were clinical response at end of treatment and evaluation of surotomycin safety. The key secondary endpoints were clinical response over time and sustained clinical response through a 30- to 40-day follow-up period. Clostridium difficile infection recurrence during follow-up and time to diarrhea resolution were also analyzed. RESULTS:In total, 570 subjects were randomized and had confirmed CDI; 290 subjects received surotomycin and 280 subjects received vancomycin. Surotomycin clinical cure rates at end of treatment (surotomycin/vancomycin: 79.0%/83.6%; difference of -4.6%; 95% confidence interval, -11.0 to 1.9]), clinical response over time (stratified log-rank test, P = .832), and sustained clinical response at end of trial (Day 40-50) (60.6%/61.4%; difference of -0.8%; 95% CI, -8.8 to 7.1) in the microbiological modified intent to treat population did not meet noninferiority or superiority criteria versus vancomycin. Both treatments were generally well tolerated. CONCLUSIONS:Surotomycin failed to meet the criteria for noninferiority versus vancomycin for the primary and key secondary endpoints in this trial.

SUBMITTER: Boix V

PROVIDER: S-EPMC5414029 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With <i>Clostridium difficile</i> Infection.

Boix Vicente V Fedorak Richard N RN Mullane Kathleen M KM Pesant Yves Y Stoutenburgh Uschi U Jin Mandy M Adedoyin Adedayo A Chesnel Laurent L Guris Dalya D Larson Kajal B KB Murata Yoshihiko Y

Open forum infectious diseases 20170119 1

<h4>Background</h4>Although the incidence of <i>Clostridium difficile</i> infection (CDI) is increasing, available CDI treatment options are limited in terms of sustained response after treatment. This phase 3 trial assessed the efficacy and safety of surotomycin, a novel bactericidal cyclic lipopeptide, versus oral vancomycin in subjects with CDI.<h4>Methods</h4>In this randomized, double-blind, active-controlled, multicenter, international trial, subjects with CDI confirmed by a positive toxin ...[more]

PMID: 28480267

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Project description:BackgroundClostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection.MethodsWe did a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) to receive oral ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was achievement of a sustained clinical response, defined as clinical cure at the end of treatment and no recurrence within 30 days, which was used to establish non-inferiority (15% margin) of ridinilazole versus vancomycin. The primary efficacy analysis was done on a modified intention-to-treat population comprising all individuals with C difficile infection confirmed by the presence of free toxin in stool who were randomly assigned to receive one or more doses of the study drug. The study is registered with ClinicalTrials.gov, number NCT02092935.FindingsBetween June 26, 2014, and August 31, 2015, 100 patients were recruited; 50 were randomly assigned to receive ridinilazole and 50 to vancomycin. 16 patients did not complete the study, and 11 discontinued treatment early. The primary efficacy analysis included 69 patients (n=36 in the ridinilazole group; n=33 in the vancomycin group). 24 of 36 (66·7%) patients in the ridinilazole group versus 14 of 33 (42·4%) of those in the vancomycin group had a sustained clinical response (treatment difference 21·1%, 90% CI 3·1-39·1, p=0·0004), establishing the non-inferiority of ridinilazole and also showing statistical superiority at the 10% level. Ridinilazole was well tolerated, with an adverse event profile similar to that of vancomycin: 82% (41 of 50) of participants reported adverse events in the ridinilazole group and 80% (40 of 50) in the vancomycin group. There were no adverse events related to ridinilazole that led to discontinuation.InterpretationRidinilazole is a targeted-spectrum antimicrobial that shows potential in treatment of initial C difficile infection and in providing sustained benefit through reduction in disease recurrence. Further clinical development is warranted.FundingWellcome Trust and Summit Therapeutics.

Dataset Information

Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With Clostridium difficile Infection.

Publications

Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With <i>Clostridium difficile</i> Infection.

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