NCT05077085

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jan 2022

Typical duration for phase_4

Geographic Reach
1 country

4 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 21, 2021

Completed
22 days until next milestone

First Posted

Study publicly available on registry

October 13, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

January 1, 2022

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2024

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2024

Completed
Last Updated

March 28, 2023

Status Verified

March 1, 2023

Enrollment Period

2.5 years

First QC Date

September 21, 2021

Last Update Submit

March 24, 2023

Conditions

Clostridium InfectionsClostridioides DifficileEnterocolitis, Pseudomembranous

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (10)

  • Initial cure after treatment with bezlotoxumab or FMT

    2 days after end of treatment

  • Recurrence after initial treatment with bezlotoxumab or FMT

    12 weeks

  • Sustained cure after initial treatment with bezlotoxumab or FMT

    12 weeks

  • Adverse events

    12 weeks

  • Post-treatment IBS-like symptoms

    12 weeks

  • +5 more secondary outcomes

Other Outcomes (2)

  • Patient wellbeing

    Pre-treatment and 12 weeks

  • Rate of patients with improved defecation pattern

    12 weeks

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: BezlotoxumabDrug: Vancomycin oral

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

ACTIVE COMPARATOR

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.

Procedure: Fecal Microbiota Transplantation (FMT)Drug: Vancomycin oral

Interventions

BezlotoxumabDRUG

single intravenous infusion of bezlotoxumab 10 mg/kg

Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy.
Fecal Microbiota Transplantation (FMT)PROCEDURE

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

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

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

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

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Amsterdam University Medical Centers, AMC

Amsterdam, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Haaglanden Medical Center

The Hague, Netherlands

Location

MeSH Terms

Conditions

Clostridium InfectionsEnterocolitis, Pseudomembranous

Interventions

bezlotoxumabFecal Microbiota TransplantationVancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsEnterocolitisGastroenteritisGastrointestinal DiseasesDigestive System DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

Biological TherapyTherapeuticsGlycopeptidesGlycoconjugatesCarbohydratesPeptidesAmino Acids, Peptides, and Proteins

Study Officials

  • J van Prehn

    Leiden University Medical Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Multicenter open label randomized controlled trial
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical Microbiologist

Study Record Dates

First Submitted

September 21, 2021

First Posted

October 13, 2021

Study Start

January 1, 2022

Primary Completion

July 1, 2024

Study Completion

December 1, 2024

Last Updated

March 28, 2023

Record last verified: 2023-03

Data Sharing

IPD Sharing
Will not share

Locations

NL(4)