Fecal Microbiota Transplantation for Primary Clostridium Difficile Diarrhea

Study Overview
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Brief Summary
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Clostridium difficile associated diarrhea (CDAD) is a significant cause of morbidity and mortality, caused by loss of healthy gut flora. Conventional treatment uses antibiotics to kill Clostridium difficile. A novel treatment uses replacement of gut flora by fecal microbiota transplant (FMT). Randomized trials have established safety and efficacy of FMT in recurrent CDAD, but no trial has used FMT for primary CDAD. This study will randomize patients to oral encapsulated FMT or oral Vancomycin.

Detailed Description
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Patients with primary CDAD will be approached for consent and randomized equally to two arms: oral FMT with oral Vancomycin placebo, or oral FMT placebo with oral Vancomycin. FMT will be prepared from anonymous donors screened according to Health Canada guidelines and stored frozen.

Official Title
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Fecal Microbiota Transplantation for Primary Therapy in Clostridium Difficile Diarrhea - A Placebo-blinded Randomized Clinical Trial

Conditions
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Clostridium Difficile

Intervention / Treatment
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* Biological: Fecal Microbiota Transplantation
* Drug: Vancomycin
* Biological: Fecal Microbiota Transplantation Placebo
* Drug: Vancomycin Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: life expectancy > 3 months, 3 or more unformed stools in 24 hours prior to randomization, positive stool test within 72 hours of randomization Exclusion Criteria: pregnancy, previous stool test positive within 12 months, toxic megacolon or ileus, already received >4 doses of treatment for current episode, inflammatory bowel disease, gastrointestinal surgery within 90 days of randomization (except appendectomy or cholecystectomy), documented aspiration of gastric contents within 90 days of randomization, requirement for treatment with oral probiotics, opiates, loperamide or diphenoxylate during the study duration, anticipated use of antibiotics for any reason during the study duration, known non-CDAD concurrent gastrointestinal infection, concurrent enrollment in another clinical trial for any reason, intolerance or hypersensitivity to Vancomycin, anaphylactic reaction to any food, current induction chemotherapy, HIV infection with Cluster of Differentiation 4 (CD4) count <200, or any medical or non-medical condition considered by the investigator to preclude participation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplantation<br>Oral, encapsulated fecal microbiota transplantation | Biological: Fecal Microbiota Transplantation<br>* Oral, encapsulated FMT<br>* Other names: Stool Transplant;Drug: Vancomycin Placebo<br>* Matching placebo to Vancomycin<br>* Other names: Vancocin Placebo;|
| Active Comparator: Vancomycin<br>125 mg po qid x 10 days | Drug: Vancomycin<br>* Vancomycin po 125 mg qid x 10 days<br>* Other names: Vancocin;Biological: Fecal Microbiota Transplantation Placebo<br>* Matching placebo to FMT<br>* Other names: Stool Transplant Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Cure of diarrhea without recurrence in intention to treat population | Cure is defined as less than 3 bowel motions per day for 2 consecutive days during the 10 day treatment period. Recurrence is defined as 3 or more bowel motions within one day during the follow-up period. | 56 days | 
| Adverse Events | Number of participants with treatment-related adverse events as defined by the Medical Dictionary for Regulatory Activities. | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Cure of diarrhea without recurrence in a per protocol population | Cure is defined as less than 3 bowel motions per day for 2 consecutive days during the 10 day treatment period. Recurrence is defined as 3 or more bowel motions within one day during the follow-up period. | 56 days | 
| Efficacy: cure of diarrhea in intention to treat and per protocol populations | Cure is defined as less than 3 bowel motions per day for 2 consecutive days during the 10 day treatment period. | 10 days | 
| Efficacy: time to cure of diarrhea | Cure is defined as less than 3 bowel motions per day for 2 consecutive days during the 10 day treatment period. | 56 days | 
| Efficacy: Health status questionnaire |  | 56 days |