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

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.