Microbiota or Placebo After Antimicrobial Therapy for Recurrent C. Difficile at Home (MATCH)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Fecal Microbiota Therapy (FMT) is effective vs. placebo in the prevention of C. difficile infection recurrence.

Detailed Description
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Clostridium difficile infection (CDI) is one of the most common nosocomial infections and is increasingly seen in non-hospitalized patients. Although more than 90% of patients have symptom resolution with a course of standard antimicrobial therapy, subsequent recurrence rates range from 15-30% (after the first CDI episode) to 40-50% (after the second and subsequent episodes). Fecal microbiota transplantation (FMT) has shown promise as an adjunct to standard antimicrobial therapy, reducing recurrence among FMT recipients to 15%. The primary study goal is to assess the efficacy of FMT for the prevention of subsequent recurrent CDI, when administered after successful treatment of recurrent CDI with standard antimicrobial therapy. Secondary goals are to evaluate, the efficacy of FMT in terms of CDI severity, duration, the safety of FMT, and in the event of a positive study result, establish a mechanism for providing FMT within the VA system. This study will enroll 390 participants. Participants will be randomized (1:1 ratio) to FMT or placebo, stratified by number of prior recurrent CDI episodes (1 versus >1). They will be assessed for symptoms of CDI, other study outcomes and any treatment-related adverse events at 2, 14, 28, 42, and 56 days, and month 3, 4, 5 and 6 after administration of the study treatment. The primary outcome is recurrent CDI (definite or possible) or death within 56 days of randomization. Definite recurrence is defined as any of the following: The new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis; Other clinical symptoms including ileus, toxic megacolon, or colectomy; PLUS Laboratory confirmation of C. difficile from a stool specimen by EIA toxin test. Possible recurrence is defined as the same clinical manifestations as above, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative EIA toxin test result, or uninterpretable result).

Official Title
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CSP #2004 - Microbiota or Placebo After Antimicrobial Therapy for Recurrent C. Difficile at Home (MATCH)

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: Fecal Microbiota Therapy (FMT)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One or more episodes recurrent CDI (defined as > 3 loose/watery stools/24h for 2 consecutive days with CDI treatment, and not explained by another diagnosis PLUS laboratory confirmation of C. difficile; or ileus, or toxic megacolon PLUS laboratory confirmation of C. difficile, occurring within 90 days of a prior CDI episode with similar symptoms and laboratory confirmation) Resolution or improvement of symptoms from most recent CDI episode, defined as no longer meeting the clinical definition for CDI for a 48 hour period during treatment, including not meeting the definition again after an initial improvement Within the enrollment window: 2 days after completion of antimicrobial therapy for CDI (to allow for a washout period) to 14 days after completion of therapy or 30 days after the onset of CDI whichever is later. Age 18 years Enrolled in a VHA facility Able and willing to provide informed consent Exclusion Criteria: Unlikely to swallow capsules Pregnancy, planning to be pregnant, or breastfeeding Receipt of cytotoxic chemotherapy, intravenous or subcutaneous immune globulin, or confirmed neutropenia (absolute neutrophil count of < 1,000 cells/ L) within the past 3 months Inflammatory bowel disease or other chronic diarrheal disease/fecal incontinence predating CDI Ongoing antibiotic use other than those for the current episode of CDI Prior FMT Life expectancy of < 8 weeks Anaphylactic food allergy Active enrollment in another research study on antibiotics, probiotics, or FMT without investigators approval Presence of an ileostomy or colostomy HIV with CD4 count < 200 cells/�L in prior 3 months Decompensated cirrhosis Bone marrow/peripheral blood stem cell transplant in the past year Unlikely to follow study protocol

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Fecal Microbiota Therapy (FMT) | Drug: Fecal Microbiota Therapy (FMT)<br>* Oral capsule-delivered FMT<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Oral capsule-delivered placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent CDI (Definite or Probable) or Death | The primary outcome is recurrent CDI (definite or probable) or death within 56 days of randomization. Definite recurrence is defined as any of the following: The new onset of more than three loose or watery stools in 24 hours for two consecutive days Other clinical symptoms including ileus, toxic mega colon, or colectomy PLUS Laboratory confirmation of C. difficile from a stool specimen. Probable recurrence is defined as the same clinical manifestations as above, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative result, or uninterpretable result). | Within 56 days of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent CDI (Definite or Possible), or Death | The incidence of recurrent CDI (definite or possible) or death within 6 months of randomization. | Within 6 months of randomization | 
| Quality of Life at 56 Day | The investigators will use a brief assessment of both overall and gastrointestinal health status, using a previously validated instrument. | 56 days from randomization | 
| Number of CDI Recurrences | The number of CDI recurrences within 6 months for a patient is the count of separate CDI recurrences from randomization to 6 months after randomization. | Within 6 months of randomization | 
| Diarrhea That is Negative for C. Difficile by EIA Toxin Test and PCR | This is similar to probable recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by EIA toxin test and PCR, not episodes that are not tested or are uninterpretable. | Within 56 days of randomization | 
| Multiple Related Symptoms | An assessment for non-diarrheal manifestations of CDI such as abdominal pain, urgency, and fecal incontinence will be performed. | Within 6 months of randomization | 
| Definite Recurrent CDI | The incidence of definite recurrent CDI within 56 days of randomization. Definite recurrence is defined as any of the following: The new onset of more than three loose or watery stools in 24 hours for two consecutive days Other clinical symptoms including ileus, toxic mega colon, or colectomy PLUS Laboratory confirmation of C. difficile from a stool specimen. | Within 56 days of randomization | 
| Possible Recurrent CDI | The incidence of probable recurrent CDI within 56 days of randomization. Possible recurrence is defined as the same clinical manifestations as definite recurrent CDI, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative result, or uninterpretable result). | Within 56 days of randomization | 
| Death | The incidence of death within 56 days of randomization. | Within 56 days of randomization | 
| Diarrhea That is Negative for C. Difficile by EIA Toxin Testing But Positive by PCR | This is similar to possible recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by EIA toxin test, not episodes that are not tested or are uninterpretable. | Within 56 days of randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clinical trial, FMT, recurrent c. difficile, infectious disease, intestine, gastrointestinal, prevention, randomized, diarrhea, fecal microbiota therapy