Fecal Microbiota Transplantation by Colonoscopy for Recurrent C. Difficile Infection
Condition: Clostridium Difficile
MeSH terms: Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      In the recent past, a deep change in the epidemiology of C. difficile infection has occurred,
      with a rise in its frequency, severity, and mortality. Both the refractoriness of the
      infection to standard therapy and its probability of recurrence have also increased,
      representing a main clinical issue. Fecal microbiota transplantation (FMT) refers to the
      introduction of a liquid filtrate of stools from a healthy donor into the gastrointestinal
      tract of a patient for the treatment of specific diseases. FMT has shown outstanding results
      in the treatment of recurrent C. difficile infection. It can be performed through various
      routes: nasogastric or nasojejunal tube, upper endoscopy, retention enema, colonoscopy. In a
      recent systematic review of studies using FMT for the treatment of recurrent C. difficile
      infection, Cammarota et al. observed that lower gastrointestinal route (colonoscopy, enema)
      led to the achievement of higher eradication rates than upper delivery (gastroscopy,
      naso-gastric or naso-jejunal tube) (81-86% vs 84-93%, respectively). In a randomized clinical
      trial, Van Nood et al. showed the efficacy of FMT by nasojejunal tube in recurrent C.
      difficile infection. Up to now, data on FMT by lower route come out only by case series and
      case reports.

      The investigators' aim is to compare the efficacy of colonoscopic FMT and standard antibiotic
      therapy for the treatment of C. difficile infection in a randomized clinical trial
    

Detailed description: 
      In the recent past, a deep change in the epidemiology of C. difficile infection has occurred,
      with a rise in its frequency, severity, and mortality. Both the refractoriness of the
      infection to standard therapy and its probability of recurrence have also increased,
      representing a main clinical issue. Fecal microbiota transplantation (FMT) refers to the
      introduction of a liquid filtrate of stools from a healthy donor into the gastrointestinal
      tract of a patient for the treatment of specific diseases. FMT has shown outstanding results
      in the treatment of recurrent C. difficile infection. It can be performed through various
      routes: nasogastric or nasojejunal tube, upper endoscopy, retention enema, colonoscopy. In a
      recent systematic review of studies using FMT for the treatment of recurrent C. difficile
      infection, Cammarota et al. observed that lower gastrointestinal route (colonoscopy, enema)
      led to the achievement of higher eradication rates than upper delivery (gastroscopy,
      naso-gastric or naso-jejunal tube) (81-86% vs 84-93%, respectively). In a randomized clinical
      trial, Van Nood et al. showed the efficacy of FMT by nasojejunal tube in recurrent C.
      difficile infection. Up to now, data on FMT by lower route come out only by case series and
      case reports.

      The investigators' aim is to compare the efficacy of colonoscopic FMT and standard antibiotic
      therapy for the treatment of C. difficile infection in an open-label randomized clinical
      trial The investigators' trial should confirm the clinical results obtained by Van Nood et
      al. by using a colonoscopy approach.

      The investigators' study is an open-label randomized controlled trial, enrolling patients
      with recurrent C. difficile infection, who are candidates for further antibiotic treatment in
      accordance with guidelines. Recurrent C. difficile infection is meant as the reappearance of
      clinical symptoms and positivity of C. difficile toxin test within 8 weeks after the end of
      the previous therapy. Patients' stool will be screened for detection of parasites and enteric
      bacterial pathogens to exclude other infective pathogens. Patients with severe clinical
      features (sepsis, severe dehydration, major co-morbidities), former colectomy, high-risk of
      endoscopic complications, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS),
      viral hepatitis, AIDS or syphilis will be excluded.

      Patients will be instructed and invited to signal recurrent symptoms and diarrhea after
      treatment. Monthly clinical and lab checks will be performed for a period of six months after
      the treatment.

      Treatment procedures:

      All patients will start therapy with vancomycin for four days before of stratification, with
      random allocation (1 to 1) to one of the two treatment schemes: 1) FMT, with the infusion in
      the cecum - through the biopsy channel - of 60-120 gr (depending on production) of donated
      feces, obtained from the donor within 6 hours from transplantation, and manually homogenized
      in 100/200 ml of physiological solution; or 2) standard vancomycin-based therapy according to
      the international recommendations. Colonoscopy will be performed by an expert endoscopist,
      with mucosal biopsy (when possible) for histology examination. Patients allocated to FMT arm
      will undergo preparation for colonoscopy (four liters of a solution with saline laxatives).
      All patient will be instructed on hygiene rules to be followed at the patient's domicile to
      avoid re-infections at home. Stool donors should preferably be patient's relatives or
      intimates, must not have taken antibiotics in the last 6 months, should not present
      significant intestinal symptoms of other intestinal diseases and must result negative at the
      serum screening for viral hepatitis, AIDS or syphilis. Their stool will be tested for C.
      difficile, enteric bacteria, intestinal protozoa and helminthes pathogens.
    

Intervention name(s): Fecal Microbiota Transplantation; Standard Antibiotic Therapy; Vancomycin (before randomization)
Intervention type(s): Other; Drug; Drug
Intervention description(s): Vancomycin will be administered in all patients for 5 days before randomization. Then, patients will be randomized in FMT Group or Standard Antibiotic therapy Group. Patients in the FMT Group will stop vancomycin 24 hours before the fecal microbiota transplantation. Patients in the Standard Antibiotic Therapy Group will continue vancomycin.
Intervention MeSH terms: Anti-Bacterial Agents; Vancomycin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Fecal microbiota transplantation; Recurrent Clostridium difficile infection; Colonoscopy; Randomized clinical trial