Bezlotoxumab Versus FMT for Multiple Recurrent CDI

NCT ID: NCT05077085

Last Updated: 2023-03-28

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-31
• Study Completion Date: 2024-12-31

Brief Summary

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.

Conditions

Clostridium Infections; Clostridioides Difficile; Enterocolitis, Pseudomembranous

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Bezlotoxumab

Intervention Type: DRUG

single intravenous infusion of bezlotoxumab 10 mg/kg

Vancomycin oral

Intervention Type: DRUG

14 days vancomycin oral 125mg QID (250mg QID when 125mg not available)

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

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.

Group Type: ACTIVE_COMPARATOR

Fecal Microbiota Transplantation (FMT)

Intervention Type: PROCEDURE

single infusion of 198 cc fecal suspension (derived from 60g donor feces) via duodenal tube or coloscopy

Vancomycin oral

Intervention Type: DRUG

14 days vancomycin oral 125mg QID (250mg QID when 125mg not available)

Interventions

Bezlotoxumab

single intravenous infusion of bezlotoxumab 10 mg/kg

Intervention Type: DRUG

Fecal Microbiota Transplantation (FMT)

single infusion of 198 cc fecal suspension (derived from 60g donor feces) via duodenal tube or coloscopy

Intervention Type: PROCEDURE

Vancomycin oral

14 days vancomycin oral 125mg QID (250mg QID when 125mg not available)

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OLVG

NETWORK

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

Medical Center Haaglanden

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Joffrey van Prehn, MD, PhD

Clinical Microbiologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J van Prehn

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Amsterdam University Medical Centers, AMC

Amsterdam, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

Haaglanden Medical Center

The Hague, , Netherlands

Countries

Netherlands

Other Identifiers

BSTEP

Identifier Type: -

Identifier Source: org_study_id