Clostridium InfectionsPhase 4BSTEPNCT05077085
Bezlotoxumab Versus FMT for Multiple Recurrent CDI
A Phase 4 study testing Bezlotoxumab, Fecal Microbiota Transplantation (FMT) and Vancomycin oral in people with Clostridium Infections and Clostridioides Difficile, run by Leiden University Medical Center at 4 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Clostridium Infections, Clostridioides Difficile, Enterocolitis, Pseudomembranous
- What is being tested?
- Bezlotoxumab, Fecal Microbiota Transplantation (FMT) and Vancomycin oral
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 4 sitesNetherlands
- Study dates
- Jan 2022to Dec 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country.
Netherlands4 sites
Amsterdam University Medical Centers, AMC
Amsterdam
Leiden University Medical Center
Leiden
Erasmus Medical Center
Rotterdam
Haaglanden Medical Center
The Hague
About this study
Official title: New Treatment Strategy for Patients With Multiple Recurrent Clostridioides Difficile Infection With Bezlotoxumab as First Option
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.
- Being tested
- Bezlotoxumab, Fecal Microbiota Transplantation (FMT), Vancomycin oral
- Medical subject headings
- Clostridium Infections, Enterocolitis, Pseudomembranous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BezlotoxumabDrug
single intravenous infusion of bezlotoxumab 10 mg/kg
Fecal Microbiota Transplantation (FMT)Procedure or surgery
single infusion of 198 cc fecal suspension (derived from 60g donor feces) via duodenal tube or coloscopy
Vancomycin oralDrug
14 days vancomycin oral 125mg QID (250mg QID when 125mg not available)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Bezlotoxumab; Drug: 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. Receives: Procedure: Fecal Microbiota Transplantation (FMT); Drug: Vancomycin oral |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks (after rescue therapy if applicable)
Secondary outcomes (10)
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).
Measured: 2 days after end of treatment
Recurrence after initial treatment with bezlotoxumab or FMT
Defined as CDI relapse within 12 weeks after initial cure
Measured: 12 weeks
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.
Measured: 12 weeks
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
Measured: 12 weeks
Post-treatment IBS-like symptoms
Development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment
Measured: 12 weeks
Duration of hospitalization
Measured: 12 weeks
Rate of antibiotic use
Measured: 12 weeks
Eradication of toxigenic C. difficile
As assessed by PCR
Measured: 3 and 12 weeks
Fecal microbiota (16S) alfa- and beta-diversity
As assessed by 16S rRNA amplicon sequencing
Measured: Pre-treatment and 3 and 12 weeks
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)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2021
- Study startJan 2022 (estimated)
- Primary completionJul 2024 (estimated)
- Study completionDec 2024 (estimated)
Why it stopped: Withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clostridium InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter open label randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- OLVG, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Medical Center Haaglanden
- Responsible party
- Principal investigator, Joffrey van Prehn, MD, PhD, Leiden University Medical Center
- Investigators
- J van Prehn, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05077085
- Sponsor's protocol ID
- BSTEP
- Acronym
- BSTEP
- Status last verified
- Mar 2023
- First submitted
- 21 Sep 2021
- Last updated
- 28 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- New Treatment Strategy for Patients With Multiple Recurrent Clostridioides Difficile Infection With Bezlotoxumab as First Option
- ClinicalTrials.gov ID
- NCT05077085
- Acronym / sponsor ID
- BSTEP / BSTEP
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- OLVG, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Medical Center Haaglanden
- Study start
- Jan 2022 (estimated)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 13 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multicenter open label randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy. | Experimental | Drug: Bezlotoxumab, Drug: Vancomycin oralinitial 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. | Active comparator | Procedure: Fecal Microbiota Transplantation (FMT), Drug: Vancomycin oralfecal 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bezlotoxumabsingle intravenous infusion of bezlotoxumab 10 mg/kg | Drug | Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy. |
| Fecal Microbiota Transplantation (FMT)single infusion of 198 cc fecal suspension (derived from 60g donor feces) via duodenal tube or coloscopy | Procedure or surgery | Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy. |
| Vancomycin oral14 days vancomycin oral 125mg QID (250mg QID when 125mg not available) | Drug | Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy., Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy. |
Primary outcome
Global cure of the treatment strategy
Time frame: 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.
10 secondary outcomes
Initial cure after treatment with bezlotoxumab or FMT
Time frame: 2 days after end of treatment
Recurrence after initial treatment with bezlotoxumab or FMT
Time frame: 12 weeks
Sustained cure after initial treatment with bezlotoxumab or FMT
Time frame: 12 weeks
Adverse events
Time frame: 12 weeks
Post-treatment IBS-like symptoms
Time frame: 12 weeks
Duration of hospitalization
Time frame: 12 weeks
Rate of antibiotic use
Time frame: 12 weeks
Eradication of toxigenic C. difficile
Time frame: 3 and 12 weeks
Fecal microbiota (16S) alfa- and beta-diversity
Time frame: Pre-treatment and 3 and 12 weeks
Cost-effectiveness
Time frame: 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J van Prehn principal investigator
Leiden University Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bezlotoxumab, Fecal Microbiota Transplantation (FMT) and Vancomycin oral in people with Clostridium Infections and Clostridioides Difficile, run by Leiden University Medical Center at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global cure of the treatment strategy (time frame: 12 weeks (after rescue therapy if applicable)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2023; AzTrials last refreshed its copy on 30 Oct 2026.