Grant: Project Grant

Background: Clostridioides difficile infection (CDI) is associated with substantial morbidity and mortality because 25% of patients experience a repeat infection (rCDI). Guidelines differ on how to treat and prevent CDI because we lack randomized controlled studies. A platform trial is an efficient way to test multiple treatment and prevention strategies for CDI. Methods: We are proposing a multicentre platform trial to enrol patients with a first or second episode of CDI. Domain 1 (Treatment): participants will be randomized to one of two treatment strategies that are used in practice, but haven't been compared. The first is a four-week taper of vancomycin, which was recently found to be superior to a 14 day course of vancomycin in a trial run by our group. The comparator will be fidaxomicin, an effective treatment to prevent rCDI, but one that is costly and not universally accessible. Domain 2 (prevention): participants will be consented for a placebo-controlled prophylaxis trial of vancomycin, in the event they are re-exposed to antibiotics within six-months of their presenting episode. New participants can also join this domain. Sample sizes for both domains have been calculated and are achievable over the course of a 5-year study. The analysis will be conducted by experts using a Bayesian probability approach. The primary outcome for both studies will be the guideline definition of rCDI at 56-days. We will work with a patient partner and integrate sex and gender into analyses. Results will be disseminated widely using the CIHR integrated knowledge translation framework. Impact: a platform study allows us to answer two important questions in the treatment and prevention of CDI. This will save costs and control for some factors that could influence the outcome. We will leverage an existing network of sites with CDI trials experience. New questions will be added to the platform over time. Results will be meaningful for patients and will change guidelines.