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

Primary Purpose

Clostridium Difficile Infection

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fecal Microbiota Therapy (FMT)

Placebo

About this trial

This is an interventional prevention trial for Clostridium Difficile Infection focused on measuring FMT, recurrent c. difficile, infectious disease, intestine, clinical trial, gastrointestinal, prevention, randomized, diarrhea, fecal microbiota therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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/µL in prior 3 months
Decompensated cirrhosis
Bone marrow/peripheral blood stem cell transplant in the past year
Unlikely to follow study protocol

Sites / Locations

Minneapolis VA Health Care System, Minneapolis, MN

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

Fecal Microbiota Therapy (FMT)

Placebo

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Recurrent CDI (Definite or Possible), or Death

The incidence of recurrent CDI (definite or possible) or death 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.

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.

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.

Multiple Related Symptoms

An assessment for non-diarrheal manifestations of CDI such as abdominal pain, urgency, and fecal incontinence will be performed.

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.

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).

Death

The incidence of death 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.

Full Information

NCT ID

NCT03005379

First Posted

December 14, 2016

Last Updated

September 18, 2023

Sponsor

VA Office of Research and Development

1. Study Identification

Unique Protocol Identification Number

NCT03005379

Brief Title

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

Acronym

MATCH

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Terminated

Why Stopped

Study is terminated for futility per protocol-specified interim analysis and DMC recommendation.

Study Start Date

November 15, 2018 (Actual)

Primary Completion Date

August 30, 2022 (Actual)

Study Completion Date

January 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

VA Office of Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Clostridium Difficile Infection

Keywords

FMT, recurrent c. difficile, infectious disease, intestine, clinical trial, gastrointestinal, prevention, randomized, diarrhea, fecal microbiota therapy

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

153 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Fecal Microbiota Therapy (FMT)

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Fecal Microbiota Therapy (FMT)

Intervention Description

Oral capsule-delivered FMT

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Oral capsule-delivered placebo

Primary Outcome Measure Information:

Title

Recurrent CDI (Definite or Probable) or Death

Description

Time Frame

Within 56 days of randomization

Secondary Outcome Measure Information:

Title

Recurrent CDI (Definite or Possible), or Death

Description

The incidence of recurrent CDI (definite or possible) or death within 6 months of randomization.

Time Frame

Within 6 months of randomization

Title

Quality of Life at 56 Day

Description

The investigators will use a brief assessment of both overall and gastrointestinal health status, using a previously validated instrument.

Time Frame

56 days from randomization

Title

Number of CDI Recurrences

Description

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.

Time Frame

Within 6 months of randomization

Title

Diarrhea That is Negative for C. Difficile by EIA Toxin Test and PCR

Description

Time Frame

Within 56 days of randomization

Title

Multiple Related Symptoms

Description

An assessment for non-diarrheal manifestations of CDI such as abdominal pain, urgency, and fecal incontinence will be performed.

Time Frame

Within 6 months of randomization

Title

Definite Recurrent CDI

Description

Time Frame

Within 56 days of randomization

Title

Possible Recurrent CDI

Description

Time Frame

Within 56 days of randomization

Title

Death

Description

The incidence of death within 56 days of randomization.

Time Frame

Within 56 days of randomization

Title

Diarrhea That is Negative for C. Difficile by EIA Toxin Testing But Positive by PCR

Description

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.

Time Frame

Within 56 days of randomization

Other Pre-specified Outcome Measures:

Title

Adverse and Serious Adverse Events

Description

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.

Time Frame

Within 6 months of randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dimitri M Drekonja, MD

Organizational Affiliation

Minneapolis VA Health Care System, Minneapolis, MN

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Aasma Shaukat, MD MPH

Organizational Affiliation

Minneapolis VA Health Care System, Minneapolis, MN

Official's Role

Study Chair

Facility Information:

Facility Name

Minneapolis VA Health Care System, Minneapolis, MN

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55417-2309

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Citations:

PubMed Identifier

34154439

Citation

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.

Results Reference

result

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

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