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

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).

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 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 CD4 count < 200 cells/�L 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