Clostridium difficile infection causes serious diarrheal disease. Although several drugs are available for treatment, including
vancomycin, recurrences remain a problem.
LFF571 is a semisynthetic thiopeptide with potency against C. difficile in vitro. In this phase 2 exploratory study, we compared the safety and efficacy (based on a noninferiority analysis) of
LFF571 to those of
vancomycin used in adults with primary episodes or first recurrences of moderate C. difficile
infection. Patients were randomized to receive 200 mg of
LFF571 or 125 mg of
vancomycin four times daily for 10 days. The primary endpoint was the proportion of clinical cures at the end of
therapy in the per-protocol population. Secondary endpoints included clinical cures at the end of
therapy in the modified intent-to-treat (mITT) population, the time to
diarrhea resolution, and the recurrence rate. Seventy-two patients were randomized, with 46 assigned to receive
LFF571. Based on the protocol-specified definition, the rate of clinical cure for
LFF571 (90.6%) was noninferior to that of
vancomycin (78.3%). The 30-day sustained cure rates for
LFF571 and
vancomycin were 56.7% and 65.0%, respectively, in the per-protocol population and 58.7% and 60.0%, respectively, in the modified intent-to-treat population. Using toxin-confirmed cases only, the recurrence rates were lower for
LFF571 (19% versus 25% for
vancomycin in the per-protocol population).
LFF571 was generally safe and well tolerated. The incidence of adverse events (AEs) was higher for
LFF571 (76.1% versus 69.2% for
vancomycin), although more AEs in the
vancomycin group were suspected to be related to the study
drug (38.5% versus 32.6% for
LFF571). One patient receiving
LFF571 discontinued the study due to an AE. (This study has been registered at ClinicalTrials.gov under registration no. NCT01232595.).