Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase II/III Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin for Recurrent Clostridium Difficile Infection (CDI)
Brief Summary: 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.


Options:
A: Patient inclusion criteria

1. Age 18 years or older.
2. Able to provide informed consent.
3. Laboratory or pathology: confirmed diagnosis of recurrent CDI with symptoms (defined below) within the previous 180 days.
4. ≥ 2 episodes of CDI within 6 months and/or ongoing symptoms consistent with CDI despite treatment with oral vancomycin at a dose of at least 125 mg 4 times daily for at least 5 days.

Symptoms of CDI, diarrhea deﬁned as: 3 or more unformed bowel movements in 24 hours for a minimum of 2 days with no other causes for diarrhea. Subjects will be required to have laboratory or pathology-confirmed diagnosis of recurrent C. difficile infection where recurrence is deﬁned as return of diarrhea and positive stool test after a period of symptom resolution within 8 weeks of the first episode and has received at least a 10-day course of standard antibiotic therapy.

Patient exclusion criteria

1. Planned or actively participating in another clinical trial.
2. Patients with neutropenia with absolute neutrophil count \<0.5 x 109/L
3. Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray
4. Peripheral white blood cell count \> 30.0 x 10E9/L AND temperature \> 38.0 oC
5. Active gastroenteritis due to Salmonella, Shigella, E. coli 0157H7, Yersinia or Campylobacter.
6. Presence of colostomy
7. Unable to tolerate HBT or enema for any reason.
8. Requiring systemic antibiotic therapy for more than 7 days.
9. Actively taking Saccharomyces boulardii
10. Severe underlying disease such that the patient is not expected to survive for at least 30 days.
11. Any condition that, in the opinion of the investigator, that the treatment may pose a health risk to the subject.

Donor inclusion

1. Able to provide and sign informed consent.
2. Able to complete and sign the donor questionnaire
3. Able to adhere to fecal transplantation stool collection standard operating procedure.

Donor exclusion

1. Tested positive for any of the following: Human Immunodeficiency virus (HIV) 1/2, hepatitis IgM, hepatitis B (HBsAg), hepatitis C antibody, syphilis, human T- lymphotrophic virus (HTLV) 1/II and vancomycin resistant Enterococcus (VRE), methicillin resistant S. aureus (MRSA), Salmonella, Shigella, E.coli O157 H7, Yersinia and Campylobacter.
2. Detection of ova, parasites, C. difficile toxin, norovirus, adenovirus, rotavirus on stool examination
3. History of any type of active cancer or autoimmune disease
4. History of risk factors for acquisition of HIV, syphilis, Hepatitis B, Hepatitis C, prion or any neurological disease as determined by the donor questionnaire, appendix B.
5. History of gastrointestinal comorbidities, e.g., inflammatory bowel disease, irritable bowel syndrome, chronic constipation or diarrhea
6. Receipt of blood transfusion from a country other than Canada in preceding 6 months
7. Antibiotic use or any systemic immunosuppressive agents in the 3 months prior to stool donation
8. Receipt of any type of live vaccine within 3 months prior to stool donation
9. Ingestion of nut or shell fish 3 days preceding donation if the recipient has known allergies to these food.
10. Any current or previous medical or psychosocial condition or behaviours which in the opinion of the investigator may pose risk to the recipients or the donor
B: Inclusion Criteria:

1. Age \> 18 and \< 90 years at the time of Screening.
2. Diagnosis of at least 3 episodes of recurrent CDI, with each episode defined as presence of diarrhea (\> 3 unformed stools/24 hours) associate with positive stool Clostridium difficle toxin, occurring within 3 months of each other.
3. CDI infection under symptomatic control with \< 3 loose/unformed BM's per 24 h period for at least 2 consecutive days before procedure.
4. Those with ability to provide informed consent.

Exclusion Criteria:

1. Those with complicated CDI, defined as white blood cell\>35 or \<0.5 x 109/L, significant abdominal pain and distension with evidence of toxic megacolon or pseudomembranous colitis, hypotension defined as systolic blood pressure \< 90 mmHg unresponsive to fluid resuscitation, end organ failure, or requiring intensive care unit admission.
2. Those with chronic diarrheal illness, such as irritable bowel syndrome or inflammatory bowel disease unless they are in remission for at least 3 months prior to enrollment.
C: Inclusion Criteria:

1. Adult outpatients (age ≥18 and \<75) referred to one of the study centers after suffering a third (or further) documented episode CDI and
2. who have failed to maintain CDI cure after standard therapy with oral vancomycin.

   * Previous treatment with at least one course of tapered/pulse dose vancomycin as per SHEA-IDSA C difficile treatment guidelines or -Inability to taper or stop vancomycin without developing diarrhea requiring anti-infective therapy. -

Exclusion Criteria:

* Patients who are aged 75 years or greater.
* Patients who are pregnant
* Patients who are nursing
* Patients who are incarcerated
* Patients with cognitive impairment or severe neuropsychiatric co morbidities who are incapable of giving their own informed consent
* Patients who are immunocompromised specifically:
* HIV infection (any CD4 count)
* AIDS-defining diagnosis or CD4\<200/mm3
* Inherited/primary immune disorders
* Immunodeficient or Immunosuppressed due to medical condition/medication:
* Current or recent (\<3 most) treatment with anti-neoplastic agent
* Current or recent (\<3 mos) treatment with any immunosuppressant medications (including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil). Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll.
* Patients with a history of severe (anaphylactic) food allergy
* Patients who have previously undergone FMT
* Patients who are unwilling or unable to undergo colonoscopy
* Patients with untreated, in-situ colorectal cancer
* Patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn"s disease or microscopic colitis) or irritable bowel syndrome
* Unable to comply with protocol requirements
* Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V
* Patients with acute illness or fever on the day of planned FMT will be excluded (not undergo randomization or treatment with FMT) with the option of including that subject at a future date.
D: 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.

Answer: D