Introduction Clostridium difficile associated diarrhoea (CDAD) is a common nosocomial infection that recurs in more than 1 in 4 cases. Garey et al. found that a course of rifaximin after standard therapy reduced relapse rate though not significantly1. We aimed to confirm or refute this finding.
Design A parallel group, randomised, placebo controlled trial in 23 English hospitals.
Funding NIHR RfPB Grant PB-PG-0110–21041. Norgine supplied drug and placebo without charge.
Population age ≥18 with resolution of CDAD after treatment with metronidazole or vancomycin. CDAD diagnosis required evidence of toxin production or pseudomembranes at endoscopy. Exclusion criteria: pregnancy or breast feeding; life expectancy <4 weeks; unable to take intervention (hypersensitivity or swallowing disorder);>5 days elapsed since treatment. Randomisation was stratified by hospital using a remote, internet-based system. Participants, clinicians and researchers were blind to allocation.
Intervention Rifaximin 1200 mg daily for two weeks then 600 mg daily for two weeks, in three divided doses. Comparator: identical placebo. Primary Outcome: relapse ≤12 weeks after treatment initiation.
Sample size The planned sample size was 180 to detect a difference in relapse of 20% (30% placebo, 10% rifaximin) with 80% power, allowing for loss to follow-up of 20%. EudraCT 2012-003205-10; www.clinicaltrials.gov NCT01670149
Results Recruitment occurred December 2012–March 2015. Of 2157 patients screened, 151 were eligible, willing and randomised before funding limits were reached (74 placebo, 77 rifaximin). Primary outcome data were available on 130. Mean age was 71.9 (SD 15.3). 36% were in-patients at start of intervention. 18/61 (29.5%) on placebo relapsed within 12 weeks compared to 11/69 (15.9%) on rifaximin, a difference between groups of −13.7% (95% CI −28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6 month safety follow up 9 participants died in each group (12%). Adverse event rates were similar between groups.
Conclusion CDAD relapse rate was 13.7% lower than on placebo. The confidence interval means that lack of effect remains possible but the estimated effect size is similar to Garey’s trial, and those reported for fidaxomicin, with longer follow-up2. Age and mortality rate were higher in our trial which may reflect greater similarity to the population at risk. Comparative trials of cost effectiveness should follow.
. Garey et al. J Antimicrob Chemother 2011;66:2850–2855.
. Crook et al. CID 2012;55(S2):S93–103.
Disclosure of Interest G. Major: None Declared, L Bradshaw: None Declared, N Boota: None Declared, K Sprange: None Declared, A Jawhari: None Declared, M Diggle: None Declared, A Montgomery: None Declared, R Spiller Conflict with: Norgine Pharmaceuticals Ltd supplied product and comparator free of cost
- clostridium difficile
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