Bezlotoxumab Versus FMT for Multiple Recurrent CDI

New Treatment Strategy for Patients With Multiple Recurrent Clostridioides Difficile Infection With Bezlotoxumab as First Option

The objective of this trial is to investigate whether a treatment strategy offering bezlotoxumab before FMT in patients suffering from multiple recurrent CDI results in equal efficacy compared with a treatment strategy with initial FMT. Strategy A includes bezlotoxumab as ancillary treatment as first option, and FMT in case of failure. Option B includes FMT as ancillary treatment as first option, and antibiotic treatment with fidaxomicin in case of failure. A secondary objective is to provide a point estimate of recurrence after bezlotoxumab for the treatment of multiple recurrent CDI.

Inclusion Criteria:

• 18-90 years old
• diarrhea (3 or more unformed stools per 24h for two consecutive days; or >= 8 unformed stools per 48h) XML File Identifier: KqQEbBLRYEZjGgsIl5GcI+NXCyM= Page 10/22
• positive PCR test for toxin A/B genes and/or positive toxin EIA for current and previous episodes (low PCR cycle threshold value when only PCR performed)
• a minimum of two prior CDI episodes
• previous episode is maximum of 3 months prior to the current episode
• the current episode responds well to Standard of Care treatment (vancomycin or fidaxomicin orally).
• Assessment of the severity of the disease will be performed according to the ESCMID recommendations.
• Both mild and severe CDI will be included

Exclusion Criteria:

• Severe complicated CDI, i.e presence of: hypotension, septic shock, elevated serum lactate, ileus, toxic megacolon, bowel perforation, or any fulminant course of disease.
• ICU admission for underlying disease
• pregnancy or current desire for pregnancy
• breastfeeding
• (prolonged) use of antibiotics (other than for treatment of CDI) during the study period or directly after the intervention
• previous use of bezlotoxumab or fecal microbiota transplantation
• a history of underlying congestive heart failure (potential safety signal phase-III trail bezlotoxumab).
• Diagnosis of inflammatory bowel disease in medical history.