Multi-Centre Trial of Fresh vs. Frozen-and-Thawed FMT for Recurrent CDI

NCT01398969 | Completed Phase 2 DMC

• 1 other identifier: CDI.HBT.1
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this study is to determine the outcome of patients with recurrent CDI treated with fresh FMT versus frozen-and-thawed FMT in a randomized controlled trial. The specific objectives are to evaluate the safety of both types of FMT and to compare the clinical response, treatment failure and relapse rate in patients treated with fresh FMT compared to those treated with frozen-and-thawed FMT; also to assess the functional health and well-being of patients in each arm using a validated tool. The metagenomics will also be conducted from the stool samples collected from select patients from each arm: pre and post treatment and the matching donors. The metagenomics data will be used to determine the bacteria which may have contributed to the cure of CDI.

Conditions

Clostridium Difficile Infection

Keywords

Randomized; Double Blind; Fecal Transplant; Recurrent; Clostridium difficile infection; CDI; HBT; Diarrhea; Frozen HBT; Thawed HBT; Fecal Enema

Outcome Measures

Primary Outcomes (2)

• The evaluation of the safety of HBT

  Assessment for adverse reactions in each study group by history, physical examination, blood work at baseline, day 12, week 5 and at completion (week 13) of the study period.

  13 Weeks post HBT

• To determine the cure rate without recurrence of CDI at 13 weeks from the last HBT.

  13 Weeks post HBT

Secondary Outcomes (2)

• To determine the relapse rate of clinical and laboratory evidence of CDI within the 13-week study period in participants treated with fresh HBT in comparison to frozen thawed HBT.

  13 Weeks post HBT

• Assessment of the functional health and well-being of patients

  Up to 1 year

Study Arms (2)

Fresh FMT

EXPERIMENTAL

Participants in this arm will receive Fresh FMT via rectal administration. They will be followed for 13 weeks to assess the cure or recurrence of CDI. All other procedures between the two arms will be identical.

Biological: Fresh FMT

Frozen-and-Thawed FMT

EXPERIMENTAL

Participants in this arm will receive Frozen-and-Thawed FMT via rectal administration. They will be followed 13 weeks to assess the cure or recurrence of CDI. All other procedures between the two arms will be identical.

Biological: Frozen-and-Thawed FMT

Interventions

Fresh FMT BIOLOGICAL

Participants will receive fresh FMT (supernatant of fecal specimen mixed with water) on day 1. If cure is not reached at day 5 (+3) a repeat FMT will be performed

Also known as: Fresh Fecal Transplantation (FMT)

Fresh FMT

Frozen-and-Thawed FMT BIOLOGICAL

Participants will receive frozen-and-thawed FMT (supernatant of fecal specimen mixed with water) on day 1. If cure is not reached at day 5 (+3) a repeat FMT will be performed

Also known as: Frozen-and-Thawed Fecal Transplantation (FMT)

Frozen-and-Thawed FMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• Able to provide informed consent.
• Laboratory or pathology: confirmed diagnosis of recurrent CDI with symptoms (defined below) within the previous 180 days.
• ≥ 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.

You may not qualify if:

• Planned or actively participating in another clinical trial.
• Patients with neutropenia with absolute neutrophil count \<0.5 x 109/L
• Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray
• Peripheral white blood cell count \> 30.0 x 10E9/L AND temperature \> 38.0 oC
• Active gastroenteritis due to Salmonella, Shigella, E. coli 0157H7, Yersinia or Campylobacter.
• Presence of colostomy
• Unable to tolerate HBT or enema for any reason.
• Requiring systemic antibiotic therapy for more than 7 days.
• Actively taking Saccharomyces boulardii
• Severe underlying disease such that the patient is not expected to survive for at least 30 days.
• Any condition that, in the opinion of the investigator, that the treatment may pose a health risk to the subject.
• Able to provide and sign informed consent.
• Able to complete and sign the donor questionnaire
• Able to adhere to fecal transplantation stool collection standard operating procedure.
• 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.

Sponsors & Collaborators

• McMaster University: lead
• St. Joseph's Healthcare Hamilton: collaborator
• Hamilton Health Sciences Corporation: collaborator
• Kingston Health Sciences Centre: collaborator
• Queen's University: collaborator
• Vancouver General Hospital: collaborator

Study Sites (4)

Vancouver Coastal Health (VCHRI/VCHA) - Diamond Health Care Centre and Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

St. Joseph's Hospital

Hamilton, Ontario, L8N4A6, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Related Publications (1)

• Lee CH, Steiner T, Petrof EO, Smieja M, Roscoe D, Nematallah A, Weese JS, Collins S, Moayyedi P, Crowther M, Ropeleski MJ, Jayaratne P, Higgins D, Li Y, Rau NV, Kim PT. Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2016 Jan 12;315(2):142-9. doi: 10.1001/jama.2015.18098.

  PMID: 26757463 DERIVED

MeSH Terms

Conditions

Clostridium Infections; Recurrence; Diarrhea

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Christine Lee, MD

  St. Joseph's Healthcare Hamilton

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants received either FMT or placebo to prevent further episode of CDI following FMT

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: July 21, 2011
• Study Start: July 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: March 1, 2015
• Last Updated: June 7, 2021

Record last verified: 2015-03

Locations

CA (4)