Oral Vancomycin Followed by Fecal Transplant Versus Tapering Oral Vancomycin

NCT01226992 | Terminated Phase 2 DMC

• 2 other identifiers: UHN # 08-04409424-U0288/2-25C 124081
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Clostridium Difficile Infection; Laboratory Confirmed Clostridium Difficile Infection

Keywords

Clostridium difficile; Fecal Transplant; Recurrent Diarrhea; Abdominal distension/bloating; Fever

Outcome Measures

Primary Outcomes (1)

• A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection.

  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.

  3 years

Secondary Outcomes (1)

• A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection.

  3 years

Study Arms (2)

Fecal Transplant

EXPERIMENTAL

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

Oral Vancomycin Taper

ACTIVE COMPARATOR

2 weeks of oral vancomycin pre-treatment followed by 6-week taper of oral vancomycin

Drug: Vancomycin

Interventions

Vancomycin DRUG

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

Oral Vancomycin Taper

Fecal Transplant BIOLOGICAL

Fecal slurry 50 grams stool in 500ml normal saline

Fecal Transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• unformed feces in 24 hours for minimum 2 days OR
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5N 1Y7, Canada

Location

Related Publications (1)

• Hota SS, Sales V, Tomlinson G, Salpeter MJ, McGeer A, Coburn B, Guttman DS, Low DE, Poutanen SM. Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection: An Open-Label, Randomized Controlled Trial. Clin Infect Dis. 2017 Feb 1;64(3):265-271. doi: 10.1093/cid/ciw731. Epub 2016 Nov 9.

  PMID: 28011612 DERIVED

MeSH Terms

Conditions

Clostridium Infections; Diarrhea; Fever

Interventions

Vancomycin; Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Temperature Changes

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Biological Therapy; Therapeutics

Study Officials

• Susy Hota, MD FRCPC

  Infectious Disease, Infection Prevention and Control, Epidemiologist

  PRINCIPAL INVESTIGATOR

• Susan Poutanen, MD MPH FRCPC

  Infectious Disease, Microbiologist

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2010
• First Posted: October 22, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: December 8, 2014

Record last verified: 2014-10

Locations

CA (1)