Fecal Microbiota Transplantation for Primary Clostridium Difficile Diarrhea

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Clostridium Difficile
• Intervention / Treatment: Biological: Fecal Microbiota Transplantation; Drug: Vancomycin Placebo; Drug: Vancomycin; Biological: Fecal Microbiota Transplantation Placebo

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Memorial University of Newfoundland
• Investigators: Principal Investigator: Peter Daley, MD FRCPC, Memorial University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: June 13, 2016
• First Posted (Estimate): June 16, 2016

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: MUN-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: After analysis is completed, data will be released

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No