Abstract
Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40 (95 confidence interval [CI], 26-51; P <. 0001) compared with vancomycin through day 40. A 37 (95 CI, 2-60; P =. 037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P =. 50 vs 13-40 days), driven by 7 (1.2) fidaxomicin versus 17 (2.9) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P <. 01). Fidaxomicin has the potential to substantially improve outcomes from CDI.
| Original language | English |
|---|---|
| Journal | Clinical Infectious Diseases |
| Volume | 55 |
| Issue number | SUPPL.2 |
| Pages (from-to) | 93 - 103 |
| ISSN | 1058-4838 |
| DOIs | |
| Publication status | Published - 01.08.2012 |
Funding
Financial support. This work was supported by Optimer; the NIHR Oxford Biomedical Research Centre (to D. W. C., A. S. W., B. C. Y., N. E. S., and T. E. A. P.); and the German Federal Ministry of Research and Education (BMBF grant number 01KN1106 to O. A. C.). Potential conflicts of interest. D. W. C., T. E. A. P., A. S. W., K. W., M. M., T. J. L., O. A. C., and R. E. report that their respective institutions received per-case funding from Optimer Pharmaceuticals. D. W. C., T. E. A. P., M. M., and T. J. L. received support from Optimer Pharmaceuticals for travel to meetings for the conduct of the clinical trial or presentation of the results of the clinical trial, and T. J. L. and M. M. received honoraria from Optimer Pharmaceuticals for additional meetings and related studies on fidaxomicin. In addition, M. M. receives honoraria from Actelion, Cubist, Iroko, Merck, Novartis, NuQure, Pfizer, Salix, Sanofi, and The Medicines Company, and T. J. L. receives honoraria from Merck, Cubist Pharmaceuticals, ViroPharma, Cempra, and Iroko Pharmaceuticals and is listed on a fidaxomicin patent. S. L. G. is a part-time employee of Optimer Pharmaceuticals, receiving honoraria from and owning stock options in Cempra. O. A. C. has received research grants from Actelion, Astellas, Basilea, Bayer, Biocryst, Celgene, F2G, Genzyme, Gilead, Merck/ Schering, Miltenyi, Pfizer, Quintiles, and ViroPharma; is a consultant to Astellas, Basilea, F2G, Gilead, Merck/Schering, Optimer, and Pfizer; and has received lecture honoraria from Astellas, Gilead, Merck/Schering, and Pfizer. All other authors report no potential conflicts.
