search
Back to results

Bezlotoxumab Versus FMT for Multiple Recurrent CDI (BSTEP)

Primary Purpose

Clostridium Infections, Clostridioides Difficile, Enterocolitis, Pseudomembranous

Status
Withdrawn
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Bezlotoxumab
Fecal Microbiota Transplantation (FMT)
Vancomycin oral
Sponsored by
Leiden University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clostridium Infections

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Amsterdam University Medical Centers, AMC
  • Haaglanden Medical Center
  • Leiden University Medical Center
  • Erasmus Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

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

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

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
Recurrence after initial treatment with bezlotoxumab or FMT
Defined as CDI relapse within 12 weeks after initial cure
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.
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
Post-treatment IBS-like symptoms
Development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment
Duration of hospitalization
Rate of antibiotic use
Eradication of toxigenic C. difficile
As assessed by PCR
Fecal microbiota (16S) alfa- and beta-diversity
As assessed by 16S rRNA amplicon sequencing
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)

Full Information

First Posted
September 21, 2021
Last Updated
March 24, 2023
Sponsor
Leiden University Medical Center
Collaborators
OLVG, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Medical Center Haaglanden
search

1. Study Identification

Unique Protocol Identification Number
NCT05077085
Brief Title
Bezlotoxumab Versus FMT for Multiple Recurrent CDI
Acronym
BSTEP
Official Title
New Treatment Strategy for Patients With Multiple Recurrent Clostridioides Difficile Infection With Bezlotoxumab as First Option
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Withdrawn
Study Start Date
January 2022 (Anticipated)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center
Collaborators
OLVG, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Medical Center Haaglanden

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Infections, Clostridioides Difficile, Enterocolitis, Pseudomembranous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Multicenter open label randomized controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy.
Arm Type
Experimental
Arm Description
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.
Arm Title
Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy.
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bezlotoxumab
Intervention Description
single intravenous infusion of bezlotoxumab 10 mg/kg
Intervention Type
Procedure
Intervention Name(s)
Fecal Microbiota Transplantation (FMT)
Intervention Description
single infusion of 198 cc fecal suspension (derived from 60g donor feces) via duodenal tube or coloscopy
Intervention Type
Drug
Intervention Name(s)
Vancomycin oral
Intervention Description
14 days vancomycin oral 125mg QID (250mg QID when 125mg not available)
Primary Outcome Measure Information:
Title
Global cure of the treatment strategy
Description
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.
Time Frame
12 weeks (after rescue therapy if applicable)
Secondary Outcome Measure Information:
Title
Initial cure after treatment with bezlotoxumab or FMT
Description
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).
Time Frame
2 days after end of treatment
Title
Recurrence after initial treatment with bezlotoxumab or FMT
Description
Defined as CDI relapse within 12 weeks after initial cure
Time Frame
12 weeks
Title
Sustained cure after initial treatment with bezlotoxumab or FMT
Description
Sustained cure is defined as cure without relapse of CDI within 12 weeks after completion of the initial treatment.
Time Frame
12 weeks
Title
Adverse events
Description
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
Time Frame
12 weeks
Title
Post-treatment IBS-like symptoms
Description
Development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment
Time Frame
12 weeks
Title
Duration of hospitalization
Time Frame
12 weeks
Title
Rate of antibiotic use
Time Frame
12 weeks
Title
Eradication of toxigenic C. difficile
Description
As assessed by PCR
Time Frame
3 and 12 weeks
Title
Fecal microbiota (16S) alfa- and beta-diversity
Description
As assessed by 16S rRNA amplicon sequencing
Time Frame
Pre-treatment and 3 and 12 weeks
Title
Cost-effectiveness
Description
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)
Time Frame
12 weeks
Other Pre-specified Outcome Measures:
Title
Patient wellbeing
Description
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
Time Frame
Pre-treatment and 12 weeks
Title
Rate of patients with improved defecation pattern
Description
As assessed by personal diary
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J van Prehn
Organizational Affiliation
Leiden University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amsterdam University Medical Centers, AMC
City
Amsterdam
Country
Netherlands
Facility Name
Haaglanden Medical Center
City
Den Haag
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Bezlotoxumab Versus FMT for Multiple Recurrent CDI

We'll reach out to this number within 24 hrs