Bezlotoxumab Versus FMT for Multiple Recurrent CDI

Clostridium Infections Clinical Trial

— BSTEP  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05077085
• Other study ID #: BSTEP
• Status: Withdrawn
• Phase: Phase 4
• Start date: January 2022
• Est. completion date: December 2024

Study information

• Verified date: March 2023
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Clostridium Infections
• Enterocolitis
• Enterocolitis, Pseudomembranous
• Infections

Intervention

Drug:
• Bezlotoxumab
single intravenous infusion of bezlotoxumab 10 mg/kg

Procedure:
• Fecal Microbiota Transplantation (FMT)
single infusion of 198 cc fecal suspension (derived from 60g donor feces) via duodenal tube or coloscopy

Drug:
• Vancomycin oral
14 days vancomycin oral 125mg QID (250mg QID when 125mg not available)

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Centers, AMC	Amsterdam
Netherlands	Haaglanden Medical Center	Den Haag
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Erasmus Medical Center	Rotterdam

Sponsors (5)

Lead Sponsor	Collaborator
Leiden University Medical Center	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Medical Center Haaglanden, OLVG

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient wellbeing	As assessed by questionnaire, that includes: self rated health - 5 point scale, higher is worse outcome; happiness - 7 points scale, higher is worse outcome; optimism - 6 items; patient health questionnaire PHQ-9 - 9 items with 4 point scale, higher is worse outcome; hospital anxiety and depression scale HADS - 14 items	Pre-treatment and 12 weeks
Other	Rate of patients with improved defecation pattern	As assessed by personal diary	12 weeks
Primary	Global cure of the treatment strategy	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.	12 weeks (after rescue therapy if applicable)
Secondary	Initial cure after treatment with bezlotoxumab or FMT	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).	2 days after end of treatment
Secondary	Recurrence after initial treatment with bezlotoxumab or FMT	Defined as CDI relapse within 12 weeks after initial cure	12 weeks
Secondary	Sustained cure after initial treatment with bezlotoxumab or FMT	Sustained cure is defined as cure without relapse of CDI within 12 weeks after completion of the initial treatment.	12 weeks
Secondary	Adverse events	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: Most likely related to ancillary CDI treatment (bezlotoxumab or FMT); May be related to ancillary CDI treatment; Not related to ancillary CDI treatment	12 weeks
Secondary	Post-treatment IBS-like symptoms	Development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment	12 weeks
Secondary	Duration of hospitalization		12 weeks
Secondary	Rate of antibiotic use		12 weeks
Secondary	Eradication of toxigenic C. difficile	As assessed by PCR	3 and 12 weeks
Secondary	Fecal microbiota (16S) alfa- and beta-diversity	As assessed by 16S rRNA amplicon sequencing	Pre-treatment and 3 and 12 weeks
Secondary	Cost-effectiveness	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)	12 weeks