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

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

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.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Drug: Fecal Microbiota Therapy (FMT); Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417-2309
      • Minneapolis VA Health Care System, Minneapolis, MN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Possible or Definite Recurrent Clostridium Difficile Infection (CDI), or Death	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.	Within 56 days of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent CDI (Definite or Possible) or Death 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.	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, 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.	56 days from randomization
Frequency of 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.	Within 6 months of randomization
Diarrhea That is Negative for C. Difficile by EIA Toxin Test and Polymerase Chain Reaction (PCR)	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.	Within 56 days of randomization
Occurrence of Abdominal Pain Among All Possible CDI Recurrences.	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.	Within 6 months of randomization
Definite Recurrent CDI	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.	Within 56 days of randomization
Possible Recurrent CDI	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.	Within 56 days of randomization
Death	The occurrence 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 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.	Within 56 days of randomization
Occurrence of Urgency Among All Possible CDI Recurrences.	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.	within 6 months from randomization
Occurrence of Fecal Incontinence Among All Possible CDI Recurrences.	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).	within 6 months from randomization
Occurrence of Altering Life Style Among All Possible CDI Recurrences	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.	within 6 months of randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse and Serious Adverse Events	Safety outcomes to be collected include: Serious adverse events, with a focus on SAEs involving hospitalization (new or prolonged), and all-cause mortality; Adverse events which may be related to FMT treatment. This includes adverse events which Site Investigators consider related/possibly related to the study treatment and all adverse events which occur within 14 days of study treatment (since an aggregate analysis of events temporally linked to treatment could show a causal relationship when compared to placebo); Infectious transmissions which are plausibly linked to FMT treatment.; Development of new conditions theoretically linked to alterations in gut microbiota.	Within 6 months of randomization

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Study Chair: Dimitri M Drekonja, MD, Minneapolis VA Health Care System, Minneapolis, MN; Study Chair: Aasma Shaukat, MD MPH, Minneapolis VA Health Care System, Minneapolis, MN

Publications and helpful links

General Publications

• Drekonja DM, Shaukat A, Zhang JH, Reinink AR, Nugent S, Dominitz JA, Davis-Karim A, Gerding DN, Kyriakides TC. Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment. Clin Trials. 2021 Oct;18(5):622-629. doi: 10.1177/17407745211021198. Epub 2021 Jun 22.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2018
• Primary Completion (Actual): August 30, 2022
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 23, 2016
• First Posted (Estimated): December 29, 2016

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: diarrhea; prevention; clinical trial; FMT; randomized; infectious disease; recurrent c. difficile; intestine; gastrointestinal; fecal microbiota therapy
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections
• Other Study ID Numbers: 2004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Digital data underlying primary scientific publications from this study will be held as part of a data sharing resource maintained by the Cooperative Studies Program (CSP). Study data held for this purpose may include data, data content, format, and organization. The data may be available to the public and other VA and non-VA researchers under certain conditions and consistent with the informed consent and CSP policy which prioritize protecting subjects' privacy and confidentiality to the fullest extent possible.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No