Multicentre Blinded Comparison of Lyophilized Sterile Fecal Filtrate to Lyophilized Fecal Microbiota Transplant in Recurrent Clostridioides Difficile Infection

• ClinicalTrials.gov Identifier: NCT03806803
• Recruitment Status: Active, not recruiting
• First Posted: January 16, 2019
• Last Update Posted: October 11, 2023
• Sponsor: University of Alberta
• Collaborators: University of British Columbia; University of Calgary; McGill University
• Information provided by (Responsible Party): University of Alberta

Study Description

Brief Summary:

Fecal microbiota transplantation (FMT) is a treatment that restores the balance of gut bacteria and is the most effective treatment for patients who suffer from recurrent Clostridioides difficile infection (CDI) brought on by antibiotic use. Although highly effective, we do not understand how FMT actually works.

Freeze-dried or lyophilized fecal microbiota transplant (LFMT) has been shown to be effective. Recently, filtered fecal slurry, free of any live bacteria, has also been shown to cure 5 such patients. The advantage of the filtered fecal slurry is that it may be safer to patients as it does not contain any live bacteria. We have conducted a pilot study comparing LFMT to lyophilized sterile fecal filtrate (LSFF) in 9 patients, and found that the success rate of treatment was 80% vs 75% in these 2 groups.

Therefore we need to perform a larger multicenter study to compare LFMT to LSFF to determine the success rate of curing these patients.

Condition or disease	Intervention/treatment	Phase
Clostridia Difficile Colitis; Clostridium Difficile Diarrhea	Biological: Lyophilized fecal microbiota transplant; Biological: Lyophilized sterile fecal filtrate	Phase 2

Detailed Description:

This prospective double blind randomized study will enroll 248 patients with recurrent Clostridium difficile infection (RCDI) in a 1:1 ratio to receive either LFMT or LSFF by capsules.

Patients will receive 15 capsules at week 0 and be assessed at weeks 1, 4, 8 and 24. Blood, stool and urine samples will be collected. If the first treatment fails, patients will be given open label LFMT from the same donor. If treatment fails again, FMT will be offered in the form and route at the treating physician's discretion.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 248 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: double blind randomized
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: LFMT and LSFF appear identical. Randomization is performed by lab staff not involved in any aspect of treatment administration or care.
• Primary Purpose: Treatment
• Official Title: A Multicenter Double Blind Randomized Study Comparing the Efficacy of Lyophilized Sterile Fecal Filtrate to Lyophilized Fecal Microbiota Transplantation (FMT) in the Management of Recurrent Clostridioides Difficile Infection (CDI)
• Actual Study Start Date: March 21, 2019
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: June 2026

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: LFMT; Lyophilized fecal microbiota transplant capsules	Biological: Lyophilized fecal microbiota transplant; 15 capsules
Experimental: LSFF; Lyophilized sterile fecal filtrate capsules	Biological: Lyophilized sterile fecal filtrate; 15 capsules

Outcome Measures

Primary Outcome Measures :

1. Resolution of RCDI [ Time Frame: 8 weeks ]
   Proportion of patients without RCDI

Secondary Outcome Measures :

1. Resolution of RCDI [ Time Frame: 24 weeks ]
   Proportion of patients with sustained cure
2. Serious Adverse Events [ Time Frame: 8 weeks ]
   Mortality directly attributable to CDI or treatment
3. Serious Adverse Events [ Time Frame: 8 weeks ]
   Infection directly attributable to treatment
4. Minor Adverse Events [ Time Frame: 1 week ]
   Nausea
5. Minor Adverse Events [ Time Frame: 1 week ]
   Vomiting
6. Minor Adverse Events [ Time Frame: 1 week ]
   Abdominal discomfort
7. Difficulty swallowing capsules [ Time Frame: 1 week ]
   Reported by patients as ranging between none, moderate or severe
8. Fever [ Time Frame: 1 week ]
   Temperature of >37.8C

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• at least 3 episodes of recurrent CDI with each episode defined as 3 or more unformed stools in 24 hours associated with positive Clostridium difficile test, each occurring within 3 months of each other.
• CDI infection under symptomatic control with 3 or fewer unformed stools in 24 hours for at least 2 consecutive days prior to treatment
• Ability to provide informed consent
• Females and males must agree to effective contraception for the duration of the study

Exclusion Criteria:

• Severe or fulminant colitis
• Chronic diarrheal illnesses such as irritable bowel syndrome or inflammatory bowel disease unless under control or in remission 3 months prior to enrollment.
• Those taking or planning to take an investigational drug within 3 months of enrollment
• Chemotherapy or radiation therapy
• Oropharyngeal or significant esophageal dysphagia
• Ileus or small bowel obstruction
• Pregnant or planning to become pregnant within 3 months
• Breastfeeding or planning to breastfeed during the trial
• Active infection requiring antibiotics
• Life expectancy <6 months Those with history of total colectomy

Contacts and Locations

Locations

Canada, Alberta

University of Alberta Hospital

Edmonton, Alberta, Canada, T6G 2X8

Canada, British Columbia

University of British Columbia

Vancouver, British Columbia, Canada

University of British Columbia

Victoria, British Columbia, Canada, V8R 1J8

Canada, Quebec

Mcgill University Health Centre

Montréal, Quebec, Canada

Canada

University Of Calgary

Calgary, Canada, T2N 2T9

Sponsors and Collaborators

University of Alberta

University of British Columbia

University of Calgary

McGill University

Investigators

• Principal Investigator: Dina Kao, MD; University of Alberta

More Information

• Responsible Party: University of Alberta
• ClinicalTrials.gov Identifier: NCT03806803
• Other Study ID Numbers: Pro00087406
• First Posted: January 16, 2019
• Last Update Posted: October 11, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Clostridium Infections; Diarrhea; Infections; Signs and Symptoms, Digestive; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses