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

• Recurrent CDI (definite or probable) or death [ Time Frame: Within 56 days of randomization ]

  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).

  
  

• Recurrent CDI (definite or probable), or death [ Time Frame: Within 6 months of randomization ]
  The incidence of recurrent CDI (definite or probable) or death within 6 months of randomization.
  
  
• Quality of Life [ Time Frame: 56 days from randomization ]
  The investigators will use a brief assessment of both overall and gastrointestinal health status, using a previously validated instrument.
  
  
• Number of CDI recurrences [ Time Frame: Within 6 months of randomization ]
  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 PCR [ Time Frame: Within 56 days of randomization ]
  This is similar to probable recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by PCR, not episodes that are not tested or are uninterpretable.
  
  
• Multiple related symptoms [ Time Frame: Within 6 months of randomization ]
  An assessment for non-diarrheal manifestations of CDI such as abdominal pain, urgency, and fecal incontinence will be performed.
  
  
• Definite recurrent CDI [ Time Frame: Within 56 days of randomization ]

  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.
  
  
• Probable recurrent CDI [ Time Frame: Within 56 days of randomization ]
  The incidence of probable recurrent CDI within 56 days of randomization. Probable 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 [ Time Frame: Within 56 days of randomization ]
  The incidence of death within 56 days of randomization.
  
  

• Adverse and Serious Adverse Events [ Time Frame: Within 6 months of randomization ]

  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.
  
  

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 probable) or death within 56 days of randomization. Definite recurrence is defined as: new onset of more than 3 loose or watery stools in 24 hours for 2 consecutive days with laboratory confirmation of C. difficile from a stool specimen; or ileus, toxic megacolon or colectomy with laboratory confirmation. Probable recurrence is defined identically as above but WITHOUT laboratory confirmation of C. difficile (not tested or negative test).