Oral Vancomycin Followed by Fecal Transplant Versus Tapering Oral Vancomycin
Recurrent CDI is a growing problem with few treatment options that provide lasting effect. Fecal transplantation has been shown in several case series to be successful in controlling recurrent CDI. The current study is a non-blinded, randomized controlled trial comparing fecal transplantation with a 6 week taper of oral vancomycin for the treatment of refractory CDI. Approximately 146 patients will be enrolled over one year. Participants in the study will be followed for 120 days, and will be given the opportunity to cross over to the alternative intervention arm if a relapse in symptoms occurs. The primary outcome measure will be recurrence of toxin-confirmed CDI within 120 days of starting the intervention. Secondary outcomes include: early recurrence of symptoms within 14 days, relapse within 120 days (same strain of C. difficile), attributable mortality, hospitalization and serious adverse events.
Recurrent Clostridium Difficile Infection
Laboratory Confirmed Clostridium Difficile Infection
Biological: Fecal Transplant
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II/III Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin for Recurrent Clostridium Difficile Infection (CDI)|
- 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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: Yes ]
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.
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Fecal Transplant
2 weeks of oral vancomycin pre-treatment followed by single dose fecal transplant administered by rectal enema. Fecal transplant (slurry) consists of 50 grams healthy donor stool blended in 500ml of Normal Saline.
Biological: Fecal Transplant
Fecal slurry 50 grams stool in 500ml normal saline
Active Comparator: Oral Vancomycin Taper
2 weeks of oral vancomycin pre-treatment followed by 6-week taper of oral vancomycin
Dose: 125 mg po qid x 2 weeks then 125 mg po bid x 1 week then 125 mg po od x 1 week then 125 mg po q every other day x 1 week then 125 mg po q every third day x 1 week then discontinue Route: oral
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01226992
|Contact: Mary Jane Salpeter, RN BHA||416 340-4800 ext firstname.lastname@example.org|
|Contact: Susy Hota, MD FRCP||416 340-4800 ext email@example.com|
|University Health Network||Recruiting|
|Toronto, Ontario, Canada, M5N 1Y7|
|Contact: Mary Jane Salpeter, RN BHA 416 340-4800 ext 8353 firstname.lastname@example.org|
|Contact: Susy Hota, MD FRCPC 416 340-4800 ext 7287 email@example.com|
|Principal Investigator: Susy Hota, MD FRCPC|
|Sub-Investigator: Valerie Sales, MD FRCPC|
|Principal Investigator:||Susy Hota, MD FRCPC||Infectious Disease, Infection Prevention and Control, Epidemiologist|
|Study Director:||Susan Poutanen, MD MPH FRCPC||Infectious Disease, Microbiologist|