Clinical trial NCT05077085: Bezlotoxumab Versus FMT for Multiple Recurrent CDI
Official title: New Treatment Strategy for Patients With Multiple Recurrent Clostridioides Difficile Infection With Bezlotoxumab as First Option
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Clostridium Infections
Clostridioides Difficile
Enterocolitis, Pseudomembranous
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: OLVG
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Erasmus Medical Center
name: Medical Center Haaglanden
First posted: 2021-10-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter open label randomized controlled trial
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Global cure of the treatment strategy
timeFrame: 12 weeks (after rescue therapy if applicable)
Secondary outcomes:
measure: Initial cure after treatment with bezlotoxumab or FMT
timeFrame: 2 days after end of treatment
measure: Recurrence after initial treatment with bezlotoxumab or FMT
timeFrame: 12 weeks
measure: Sustained cure after initial treatment with bezlotoxumab or FMT
timeFrame: 12 weeks
measure: Adverse events
timeFrame: 12 weeks
measure: Post-treatment IBS-like symptoms
timeFrame: 12 weeks
measure: Duration of hospitalization
timeFrame: 12 weeks
measure: Rate of antibiotic use
timeFrame: 12 weeks
measure: Eradication of toxigenic C. difficile
timeFrame: 3 and 12 weeks
measure: Fecal microbiota (16S) alfa- and beta-diversity
timeFrame: Pre-treatment and 3 and 12 weeks
measure: Cost-effectiveness
timeFrame: 12 weeks
Other outcomes:
measure: Patient wellbeing
timeFrame: Pre-treatment and 12 weeks
measure: Rate of patients with improved defecation pattern
timeFrame: 12 weeks
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centers, AMC
city: Den Haag
country: Netherlands
facility: Haaglanden Medical Center
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: J van Prehn
role: PRINCIPAL_INVESTIGATOR
References: