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

Phase 2

Terminated

• Conditions: Clostridium Difficile Infection
• Interventions: Drug: Placebo; Drug: Fecal Microbiota Therapy (FMT)

• Registration Number: NCT03005379
• Lead Sponsor: VA Office of Research and Development

Brief Summary

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

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 toxin Enzyme Immunoassays (EIA) 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).

Study Timeline

• Study First Submitted: 2016-12-14
• Study First Submitted QC: 2016-12-23
• Study First Posted: 2016-12-29
• Study Start: 2018-11-15
• Primary Completion: 2022-08-30
• Study Completion: 2023-01-31
• Results First Submitted: 2023-08-23
• Results First Submitted QC: 2023-09-18
• Results First Posted: 2023-10-11
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-14
• Last Update Posted: 2024-04-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 153

Inclusion Criteria

1. 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)
2. 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
3. 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.
4. Age 18 years
5. Enrolled in a Veterans Health Administration (VHA) facility
6. Able and willing to provide informed consent

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Exclusion Criteria

1. Unlikely to swallow capsules
2. Pregnancy, planning to be pregnant, or breastfeeding
3. 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
4. Inflammatory bowel disease or other chronic diarrheal disease/fecal incontinence predating CDI
5. Ongoing antibiotic use other than those for the current episode of CDI
6. Prior FMT
7. Life expectancy of < 8 weeks
8. Anaphylactic food allergy
9. Active enrollment in another research study on antibiotics, probiotics, or FMT without investigators approval
10. Presence of an ileostomy or colostomy
11. HIV with Clusters of Differentiation 4 (CD4) cell count < 200 cells/µL in prior 3 months
12. Decompensated cirrhosis
13. Bone marrow/peripheral blood stem cell transplant in the past year
14. Unlikely to follow study protocol

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Placebo
1	Fecal Microbiota Therapy (FMT)	Fecal Microbiota Therapy (FMT)

Primary Outcome Measures

Name	Time	Method
Possible or Definite Recurrent Clostridium Difficile Infection (CDI), or Death	Within 56 days of randomization	The primary outcome is recurrent CDI (definite or possible) or death within 56 days of randomization.; A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (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 toxin Enzyme Immunoassays (EIA) test.

Secondary Outcome Measures

Name	Time	Method
Frequency of Possible CDI Recurrences Within 6 Months of Randomization	Within 6 months of randomization	A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
Definite Recurrent CDI	Within 56 days of randomization	The occurrence of definite recurrent CDI within 56 days of randomization. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (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.
Occurrence of Urgency Among All Possible CDI Recurrences.	within 6 months from randomization	A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced urgency in each of their possible CDI recurrences. The urgency is defined as the urgent need to pass stool, feelings of incomplete bowel control, or inability to control defecation.
Diarrhea That is Negative for C. Difficile by EIA Toxin Test and Polymerase Chain Reaction (PCR)	Within 56 days of randomization	This is similar to a possible recurrent CDI, but includes only episodes of diarrhea that are tested negative for C. difficile by EIA toxin test and PCR. A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
Occurrence of Abdominal Pain Among All Possible CDI Recurrences.	Within 6 months of randomization	A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced abdominal pain in each of their possible CDI recurrences.
Possible Recurrent CDI	Within 56 days of randomization	The occurrence of possible recurrent CDI within 56 days of randomization. A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
Recurrent CDI (Definite or Possible) or Death Within 6 Months of Randomization.	Within 6 months of randomization	A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (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.
Quality of Life at 56 Day	56 days from randomization	The investigators will use a brief assessment of both overall and gastrointestinal health status, a previously validated instrument called Gastrointestinal Quality of Life Index (GIQLI). GIQLI takes value between 0 and 144, with higher score associated with better quality of life.
Death	Within 56 days of randomization	The occurrence of death within 56 days of randomization.
Diarrhea That is Negative for C. Difficile by EIA Toxin Testing But Positive by PCR	Within 56 days of randomization	This is similar to possible recurrent CDI, but includes only episodes of diarrhea that are tested negative for C. difficile by EIA toxin test but positive by PCR. A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
Occurrence of Fecal Incontinence Among All Possible CDI Recurrences.	within 6 months from randomization	A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced fecal incontinence in each of their possible CDI recurrences. Fecal incontinence is defined as having unintentional passing of stool (liquid or solid).
Occurrence of Altering Life Style Among All Possible CDI Recurrences	within 6 months of randomization	A possible CDI recurrence is defined as a 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. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they had to alter their life style (such as using pads) in each of the possible CDI recurrence.

Trial Locations

Locations (1)

Minneapolis VA Health Care System, Minneapolis, MN; 🇺🇸 Minneapolis, Minnesota, United States