818. Efficacy and Safety of Oral Vancomycin (V) Versus Oral Metronidazole (M) for Treatment of Clostridium difficile Associated Diarrhea (CDAD): Pooled Results from Two Randomized Clinical Trials
Session: Poster Abstract Session: Antimicrobial Chemotherapy
Friday, October 19, 2012
Room: SDCC Poster Hall F-H
Background: V and M are commonly used for treatment of CDAD (aka, CDI). Head-to-head trials are limited but data suggest improved outcomes in patients with severe CDAD treated with V. Tolevamer, a “toxin-binding resin,” was inferior to V and M in two large randomized clinical trials. We compared V vs M for CDAD from these trials.

Methods: Data were pooled, in a post-hoc analysis, from 2 Phase 3, multi-center, randomized, double-blind, double-dummy, active control, parallel-design efficacy and safety trials at 209 sites. Subjects with primary or recurrent CDAD were treated with V (125mg QID) or M (375mg QID) for 10 days with 4-wk follow up.  The primary end-point was resolution of diarrhea and abdominal pain (clinical success). Secondary evaluations included time to resolution of diarrhea (TTROD), recurrence of CDAD, and adverse events (AEs). Treatments were compared via logistic and proportional hazards regression models and uni- and multivariate logistic regression analysis (OR 95% CI) was performed to assess potential factors impacting the primary outcome. Kaplan-Meier estimates were used for TTROD.

Results: 537 subjects were evaluated for efficacy (V: 259; M: 278); 53% age > 65 yrs, 29% had severe CDAD, 78% were being treated for primary CDAD, and 23% had infection due to a BI strain (aka, NAP1/027). Overall, V significantly improved clinical success [81.1% vs 72.7%; OR (95% CI): 1.681 (1.114, 2.537), p= 0.0134]. Factors associated with clinical success included treatment naïve status, primary CDAD, and mild/moderate CDAD. In multivariate analysis, treatment with V, treatment naïve status, and mild/moderate disease severity remained significantly associated with clinical success. Median TTROD was similar between groups (5 days). Recurrence rates were 20.6% (V) and 23.0% (M). The proportion of subjects reporting related treatment emergent AEs was similar between groups. AE discontinuations were more frequent with M (11.2% vs 6.5%). More subjects experienced nephrotoxicity-related AEs with V [n=12 (4.6%)] than M [n=3 (1.0%)], predominantly among older subjects.

Conclusion: CDAD clinical success was statistically superior for V compared to M in the largest multicenter, randomized, blinded, head-to-head clinical trials conducted to date.

Stuart Johnson, MD, FIDSA1,2, Dale Gerding, MD, FIDSA2,3, David Davidson, MD4, Thomas J Louie, M D5, Oliver A Cornely, MD, FIDSA6, David Fitts7, Stephen Gelone, PharmD8 and Colin Broom, MD7, (1)Edward Hines, Jr. VA Hospital, Hines, IL, (2)Loyola University Chicago Stritch School of Medicine, Maywood, IL, (3)Hines VA Hospital, Hines, IL, (4)Bluebirdbio, Cambridge, MA, (5)University of Calgary, Calgary, AB, Canada, (6)Uniklinik koln, Cologne, Germany, (7)ViroPharma Incorporated, Exton, PA, (8)ViroPharma, Inc., Exton, PA

Disclosures:

S. Johnson, ViroPharma: Consultant, Consulting fee

D. Gerding, Viropharma: Consultant, Investigator and Patents licensed to ViroPharma, Consulting fee and Grant recipient

D. Davidson, None

T. J. Louie, None

O. A. Cornely, Astellas: Consultant, Grant Investigator, Research Contractor, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
Gilead: Consultant, Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
Merck/MSD: Consultant, Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
Pfizer: Consultant, Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium

D. Fitts, ViroPharma Incorporated: Employee, Salary

S. Gelone, ViroPharma Incorporated: Employee, Salary

C. Broom, ViroPharma Incorporated: Employee, Salary

Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 17th with the exception of research findings presented at the IDWeek press conferences.