Bezlotoxumab Versus FMT for Multiple Recurrent CDI (BSTEP)

Leiden University Medical Center (LUMC)

Status and phase: Withdrawn; Phase 4

Conditions: Enterocolitis, Pseudomembranous; Clostridium Infections; Clostridioides Difficile

Treatments: Drug: Vancomycin oral; Procedure: Fecal Microbiota Transplantation (FMT); Drug: Bezlotoxumab

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT05077085

BSTEP

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy.

Experimental group

Description:

initial bezlotoxumab in addition to 14 days SoC oral antibiotic treatment with vancomycin 125 mg QID. 14 days of vancomycin 125mg QID plus fecal microbiota in case of treatment failure.

Treatment:

Drug: Bezlotoxumab

Drug: Vancomycin oral

Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy.

Active Comparator group

Description:

fecal microbiota transplantation in addition to 14 days SoC oral antibiotic treatment with vancomycin 125 mg QID. 10 days of fidaxomicin 200 mg BID in case of treatment failure.

Treatment:

Procedure: Fecal Microbiota Transplantation (FMT)

Drug: Vancomycin oral