Fecal Transplantation for Primary Clostridium Difficile Infection
Fecal Transplantation for Primary Clostridium Difficile Infection
In this randomized controlled trial the investigators want to compare the effect of one-time
 rectal instillation of fecal microbiota transplantation, compared to a ten-day antibiotic
 course for the treatment of primary Clostridium difficile infection (CDI). The investigators
 hypothetsize that the instillation of feces from a healthy donor will be non-inferior to
 vancomycin in inducing a durable cure.
Up to one third of patients with clostridium difficile infection treated with antibiotics
 experience recurrent or relapsing symptoms within a few weeks. Even with subsequent
 antibiotic treatment, multiple recurrences/relapses are frequent. Fecal microbiota
 transplantation (FMT) has been shown to be significantly more effective in curing recurrent
 CDI than repeated antibiotic treatment. In current guidelines, FMT is proposed as a treatment
 option after multiple recurrences/relapses of CDI. The rationale to reserve transplantation
 of donor feces for recurrent and difficult cases of CDI is a possible risk of pathogen
 transmittance and the process of finding a donor and screen for communicable disease.

 The effect of FMT for recurrent CDI, however, suggests that this therapy may be more
 effective than antibiotics in inducing a durable cure also for primary CDI. If the
 therapeutic effect of FMT proves to be equal (non-inferior) or more effective than
 antibiotics, FMT may be the preferable treatment option due to favourable ecological impact
 compared to antibiotics. In an era with increasing concerns about overuse of antibiotics and
 emergence of antibiotic resistant bacteria, it is important to investigate therapeutic
 alternatives that may reduce the need for antibiotics.

 This trial is a phase III multicentre, randomized controlled, open-label non-inferiority
 parallel group trial with two arms (FMT and antibiotics), and is a continuation of the phase
 II trial IMT for Primary Clostridium Difficile Infection (NCT02301000). In the current trial,
 patients with Clostridium difficile infection and no previous CDI within 12 months prior to
 inclusion will be randomized 1:1 to FMT or 10 days of guideline-recommended antibiotic
 therapy (vancomycin 125 mg four times a day).

 Patients are recruited in Norwegian hospitals.

 The investigators plan to use frozen microbiota, because supply is easier to organize,
 compared to fresh fecal samples. Patients in the FMT treatment group will receive one rectal
 dose of FMT, originating from screened, healthy donors. Patients who are not cured by the
 first dose is offered a protocol defined additional FMT treatment. In the case of clinical
 deterioration, appropriate measures will be undertaken according to current guidelines.

 Patient treatment outcomes are evaluated after 14, 60 and 365 days from inclusion and
 treatment initiation.

 An interim analysis is planned after inclusion of the first 94 patients (corresponding to 50%
 of the planned number of patients).
Inclusion Criteria:

 -  Patients, ≥18 years with primary C. difficile infection, defined by the following
 three criteria:

 1. Diarrhea as defined by the WHO (≥3 loose stools per day), and

 2. Positive stool test for toxin producing C. difficile, and

 3. No evidence of previous C. difficile infection during 365 days before enrolment.

 -  Written informed consent

 Exclusion Criteria:

 -  Known presence of other stool pathogens known to cause diarrhea.

 -  Ongoing antibiotic treatment for other infections that cannot be stopped before study
 treatment administration.

 -  Inflammatory bowel disease or microscopic colitis.

 -  < 3 months life expectancy.

 -  Serious immunodeficiency, defined as one of the following:

 -  Ongoing or recent chemotherapy and current or expected neutropenia with
 neutrophil count of < 500/μL.

 -  Active severe immunocompromising disease.

 -  Inability to comply with protocol requirements.

 -  Need of intensive care.

 -  Known irritable bowel syndrome, diarrheal type.

 -  Pregnancy or nursing.

 -  Known or suspected toxic megacolon or ileus.

 -  Total or subtotal colectomy, ileostomy or colonostomy.

 -  Contraindications for rectal catheter insertion

 -  Known hypersensitivity or other contraindications to vancomycin