Oral Vancomycin Followed by Fecal Transplant Versus Tapering Oral Vancomycin

• A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection. [ Time Frame: 3 years ]
  To assess the number of patients with recurrence of laboratory-confirmed CDI in the 120 days following completion of intervention with either oral vancomycin followed by fecal transplantation or a 6-week taper of oral vancomycin.
  
  

• A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection. [ Time Frame: 3 years ]

  To evaluate the safety profile of fecal transplantation.

  To characterize other outcomes of patients treated with fecal transplantation and oral vancomycin, as determined by the following:

  i. Early (within 14 days of treatment completion) and late (within 120 days of treatment) recurrence of symptoms compatible with CDI; ii. Days with diarrhea in the 120 days post-treatment; iii. CDI requiring hospital admission in the 120 days after treatment onset; iv. All-cause and CDI-attributable mortality; v. Recurrence of CDI in the 120 days after crossover to the alternate treatment arm.

  
  

The proposed trial is a single-centre, phase II/III, open, parallel-group, randomized controlled trial. To have an evaluable population of 114 participants and assuming a 20% loss to follow-up, approximately 146 patients will be randomized in a 1:1 ratio to receive either approximately 2 weeks of oral vancomycin followed by a single fecal transplant via enema (hereon referred to as the "fecal transplant arm") or a 6-week taper of oral vancomycin (hereon referred to as the "vancomycin taper arm"). The 2 weeks of vancomycin pre-treatment in the fecal transplant arm will allow for a fecal transplant donor to be screened for potentially transmissible infectious diseases (clinically and through blood and stool tests), in order to ensure appropriateness and safety of donation.

If patients fail treatment during the follow-up period of 120 days, they will be offered the opportunity to cross over to the alternate treatment arm. Those who cross over will be followed for an additional 120 days from the second intervention.

Participants will be assessed clinically for recurrence in CDI symptoms and adverse events at the following time points after the intervention: 4 days, 7 days, 3 weeks, 6 weeks, 12 weeks and 16 weeks. All recurrences of CDI symptoms will be investigated with C. difficile laboratory testing to confirm the etiology of these symptoms.

Analysis will be intention to treat. An interim analysis may take place after completion of follow-up of 30 patients. This interim analysis is meant to establish the safety and feasibility of the study, not measure efficacy. Although there were no formal sample size calculations to assess safety of the procedure, with a sample size of 70 participants, an adverse event rate, for example of 2.5%, can be detected with a probability of 0.83 for the fecal transplantation group.