Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial
The Lancet Infectious Diseases, 03/27/2012
Cornely OA et al. – Fidaxomicin could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin.Methods
- In this multicentre, double-blind, randomised, non-inferiority trial, the authors enrolled patients from 45 sites in Europe and 41 sites in the USA and Canada between April 19, 2007, and Dec 11, 2009.
- Eligible patients were aged 16 years or older with acute, toxin-positive C difficile infection.
- Patients were randomly allocated (1:1) to receive oral fidaxomicin (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days.
- The primary endpoint was clinical cure, defined as resolution of diarrhoea and no further need for treatment.
- An interactive voice-response system and computer-generated randomisation schedule gave a randomisation number and medication kit number for each patient.
- Participants and investigators were masked to treatment allocation.
- Non-inferiority was prespecified with a margin of 10%.
- Modified intention-to-treat and per-protocol populations were analysed.
- Of 535 patients enrolled, 270 were assigned fidaxomicin and 265 vancomycin.
- After 26 patients were excluded, 509 were included in the modified intention-to-treat (mITT) population.
- 198 (91•7%) of 216 patients in the per-protocol population given fidaxomicin achieved clinical cure, compared with 213 (90•6%) of 235 given vancomycin, meeting the criterion for non-inferiority (one-sided 97.5% CI -4.3%).
- Non-inferiority was also shown for clinical cure in the mITT population, with 221 (87.7%) of 252 patients given fidaxomicin and 223 (86.8%) of 257 given vancomycin cured (one-sided 97.5% CI -4.9%).
- nalyses of the primary endpoint in the mITT population, outcomes in the two treatment groups did not differ significantly; although patients receiving concomitant antibiotics for other infections had a higher cure rate with fidaxomicin (46 [90.2%] of 51) than with vancomycin (33 [73.3%] of 45; p=0.031).
- Occurrence of treatment-emergent adverse events did not differ between groups. 20 (7.6%) of 264 patients given at least one dose of fidaxomicin and 17 (6.5%) of 260 given vancomycin died.