Bezlotoxumab Versus FMT for Multiple Recurrent CDI
- Conditions
- Clostridium InfectionsClostridioides DifficileEnterocolitis, Pseudomembranous
- Interventions
- Registration Number
- NCT05077085
- Lead Sponsor
- Leiden University Medical Center
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy. Bezlotoxumab 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. Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy. Vancomycin oral 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. Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy. Fecal Microbiota Transplantation (FMT) 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. Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy. Vancomycin oral 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.
- Primary Outcome Measures
Name Time Method Global cure of the treatment strategy 12 weeks (after rescue therapy if applicable) Defined as cure without relapse of CDI within 12 weeks after completion of the treatment strategy in the study arm, i.e. after completion of secondary treatment in case of failure on initial treatment.
- Secondary Outcome Measures
Name Time Method Post-treatment IBS-like symptoms 12 weeks Development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment
Fecal microbiota (16S) alfa- and beta-diversity Pre-treatment and 3 and 12 weeks As assessed by 16S rRNA amplicon sequencing
Cost-effectiveness 12 weeks Costs per cured patient (global and sustained cure) and costs per QALY gained, using the EQ-5D-5L health questionaire that assesses five domains by 5 point scale, e.g. no/slight/moderate/severe/extreme impairment and a visual analogue 0-100 scale of health rating, higher is better)
Initial cure after treatment with bezlotoxumab or FMT 2 days after end of treatment Defined as cure after completion of the primary CDI treatment in the study arm. Initial cure is assessed at day 2 after end of treatment (EOT).
Rate of antibiotic use 12 weeks Recurrence after initial treatment with bezlotoxumab or FMT 12 weeks Defined as CDI relapse within 12 weeks after initial cure
Sustained cure after initial treatment with bezlotoxumab or FMT 12 weeks Sustained cure is defined as cure without relapse of CDI within 12 weeks after completion of the initial treatment.
Adverse events 12 weeks Throughout the entire study all adverse events will be noted. After the final study procedure of the last patient, all adverse events will be categorized:
1. Most likely related to ancillary CDI treatment (bezlotoxumab or FMT)
2. May be related to ancillary CDI treatment
3. Not related to ancillary CDI treatmentDuration of hospitalization 12 weeks Eradication of toxigenic C. difficile 3 and 12 weeks As assessed by PCR
Trial Locations
- Locations (4)
Haaglanden Medical Center
🇳🇱Den Haag, Netherlands
Amsterdam University Medical Centers, AMC
🇳🇱Amsterdam, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands