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| Name | Class |
|---|---|
| OLVG | NETWORK |
| Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | OTHER |
| Erasmus Medical Center | OTHER |
| Medical Center Haaglanden |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bezlotoxumab | Drug | single intravenous infusion of bezlotoxumab 10 mg/kg |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Recurrence after initial treatment with bezlotoxumab or FMT |
| Measure | Description | Time Frame |
|---|---|---|
| Patient wellbeing | As assessed by questionnaire, that includes:
| Pre-treatment and 12 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| J van Prehn | Leiden University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amsterdam University Medical Centers, AMC | Amsterdam | Netherlands | ||||
| Leiden University Medical Center |
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| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| D004761 | Enterocolitis, Pseudomembranous |
| ID | Term |
|---|---|
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000613978 | bezlotoxumab |
| D000069467 | Fecal Microbiota Transplantation |
| D014640 | Vancomycin |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
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| OTHER |
Multicenter open label randomized controlled trial
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| Fecal Microbiota Transplantation (FMT) | Procedure | single infusion of 198 cc fecal suspension (derived from 60g donor feces) via duodenal tube or coloscopy |
|
| Vancomycin oral | Drug | 14 days vancomycin oral 125mg QID (250mg QID when 125mg not available) |
|
Defined as CDI relapse within 12 weeks after initial cure |
| 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. | 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:
| 12 weeks |
| Post-treatment IBS-like symptoms | Development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment | 12 weeks |
| Duration of hospitalization | 12 weeks |
| Rate of antibiotic use | 12 weeks |
| Eradication of toxigenic C. difficile | As assessed by PCR | 3 and 12 weeks |
| Fecal microbiota (16S) alfa- and beta-diversity | As assessed by 16S rRNA amplicon sequencing | 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) | 12 weeks |
| Rate of patients with improved defecation pattern | As assessed by personal diary | 12 weeks |
| Leiden |
| Netherlands |
| Erasmus Medical Center | Rotterdam | Netherlands |
| Haaglanden Medical Center | The Hague | Netherlands |
| D004760 | Enterocolitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| D002241 |
| Carbohydrates |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |