Randomized Clinical Trial in Clostridium difficile Infection Confirms Superiority of Fidaxomicin Over Vancomycin

Abstract

The usual treatments of Clostridium difficile infection (CDI), metronidazole, or vancomycin (VAN), have cure rates of 80%-90% but 20%-30% of patients experience a relapse. This phase III, randomized, controlled trial (RCT) compared fidaxomicin (FDX), a first-in-class bacteriocidal macrocyclic antibiotic, with VAN in treatment of CDI. METHODS: Eligible patients had acute CDI symptoms and a positive stool toxin test. Patients received oral FDX (200 mg twice daily) or oral VAN (125 mg 4 times daily) for 10 days. The primary end point was clinical cure. Secondary end points were CDI recurrence (diarrhea and positive stool toxin test within 4 weeks after treatment), and global cure (clinical cure with no recurrence). RESULTS: This RCT comprised 535 subjects with 524 available for safety, 509 for modified intent-to-treat (mITT), and 451 for perprotocol (PP) analyses. Europe (39%), the United States (30%), and Canada (31%) contributed subjects from 100 clinical sites. All data are given for the PP population; the mITT population was similar in all instances. The primary noninferiority end point of cure was met with 91.7% cured vs 90.6% (FDX vs VAN, respectively). Recurrence was seen in 12.8% vs 25.3% (FDX vs VAN, respectively; P