microbiota or placebo after antimicrobial therapy for recurrent c. difficile at home (match)

Conditions: Clostridium Difficile Infection

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.

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).

Eligibility criteria:
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

Keywords: fmt recurrent c. difficile infectious disease intestine clinical trial gastrointestinal prevention randomized diarrhea fecal microbiota therapy