Clinical infection associated with Clostridium difficile (CDAI) recurs in 15-30% of patients. This multi-center, randomized, placebo-controlled study (RAPID Trial) evaluated whether post-treatment prophylaxis with ongoing rifaximin would reduce the recurrence rate. After initial therapy with metronidazole or vancomycin, 151 patients (mean 71.9 year) received placebo therapy or rifaximin 400mg three times daily for 2 weeks then 200mg three times daily for 2 weeks. Among 130 evaluable patients, recurrence within 12 weeks of study entry was more common in those receiving placebo (29.5% vs 15.9%; 95% CI −28.1% to 0.7%, p=0.06). Adverse events were similar between groups and 9 patients in each group died during further 6 month follow-up. The authors noted that rifaximin appeared to cut the recurrence rate in half, but failure to reach statistical significance was likely due, in part, to challenges reaching their recruitment target.
While this study failed to reach the necessary and planned recruitment of 180 patients prior to closure and end of funding, the authors provided a meta-analysis combining results with a similar smaller trial, yielding an overall absolute reduction in risk of CDAI recurrence of 14% (95% CI -26% to -3%; p=0.01). This is similar to the prevention of recurrence seen in recent trials of several novel and potentially costly antibiotic and monoclocal antibody therapies that were deemed cost effective when used for primary therapy and/or secondary prevention. Rifaximin is attractive because of its low systemic bioavailability and reported modest effect on fecal microbiota. Fecal transplantation is likely most efficacious for those with multiple episodes of recurrence.
Major G, Bradshaw L, Boota N, et al. Follow-on RifAximin for the Prevention of recurrence following standard treatment of Infection with Clostridium Difficile (RAPID): a randomised placebo controlled trial. Gut 2018 Sep 25. (Epub ahead of print) (https://gut.bmj.com/content/gutjnl/early/2018/09/25/gutjnl-2018-316794.full.pdf