Oral Vancomycin Followed by Fecal Transplant Versus Tapering Oral Vancomycin
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.
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.
Inclusion Criteria:

 -  Laboratory or pathology-confirmed diagnosis of recurrent C. difficile infection (CDI)
 with symptoms within the previous 60 days. Recurrent CDI is defined as:

 -  >/=2 episodes of CDI. Eligible patients must have had at least one treatment
 course with oral vancomycin (minimum 10 days of 500 mg total daily oral
 vancomycin).

 Symptoms of CDI include:

 -  Diarrhea (see below) OR

 -  Abdominal pain AND abdominal distension/bloating AND fever, systemic illness with no
 other reason for these symptoms

 Diarrhea will be self-reported and is defined as:

 -  at least 6 watery feces in 36 hours OR

 -  3 unformed feces in 24 hours for minimum 2 days OR

 -  8 unformed feces over 48 hours

 -  Age 18 years or older

 -  Signed informed consent

 -  Able to travel to clinic for follow-up visit and/or adhere to study procedures

 -  Agrees to abstain from taking probiotic supplementations for medicinal reasons
 for the duration of the study and follow-up period. To clarify, dietary intake is
 acceptable (e.g. non-supplemented yogurt).

 Exclusion Criteria:

 -  Planned participation in another clinical trial

 -  Patients with conditions such as neutropenia, graft versus host disease or severe
 immunocompromise, in whom enemas are contraindicated

 -  More than one episode of CDI that has been severe or rapid in onset, resulting in:

 -  intensive care unit admission

 -  Evidence of active, severe colitis (ie. ongoing diarrhea not responsive to oral
 vancomycin; hemorrhagic colitis) such that an enema is contraindicated (note that
 such patients may be eligible once their colitis is under control)

 -  Unable to tolerate fecal transplantation procedure for any other reason

 -  Hypersensitivity or intolerance to oral vancomycin

 -  Patients with underlying chronic gastrointestinal diseases that cause diarrhea,
 such as:

 -  Inflammatory bowel disease

 -  Short gut syndrome

 -  Severe motility disorders

 -  Severe diverticular disease

 -  Other chronic diarrhea NYD

 -  Unable to record frequency of bowel movements

 -  Receiving an investigational medication

 -  Planned therapy in the next 120 days that may cause diarrhea (example:
 chemotherapy)

 -  Planned surgery requiring perioperative antibiotics within 120 days

 -  Pregnancy

 -  Requires the regular use of medications that affect bowel motility before onset
 of CDI (example: metoclopramide, narcotics, loperamide)

 -  Serious bleeding disorder, anticoagulant use that cannot be stopped temporarily
 for procedure (in consultation with prescribing physician) or serious platelet
 disorder (platelet counts below 50).

 -  Any condition that, in the opinion of the investigator, would pose a health risk
 to the subject.