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

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)

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.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Diarrhea; Clostridia Difficile Colitis
• Intervention / Treatment: Biological: Lyophilized fecal microbiota transplant; Biological: Lyophilized sterile fecal filtrate

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 Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2N 2T9
    • University Of Calgary
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada
      • University of British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • University of British Columbia
  • Quebec
    • Montréal, Quebec, Canada
      • McGill University Health Centre

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of RCDI	Proportion of patients without RCDI	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events	Mortality directly attributable to CDI or treatment	8 weeks
Serious Adverse Events	Infection directly attributable to treatment	8 weeks
Resolution of RCDI	Proportion of patients with sustained cure	24 weeks
Minor Adverse Events	Nausea	1 week
Minor Adverse Events	Vomiting	1 week
Minor Adverse Events	Abdominal discomfort	1 week
Difficulty swallowing capsules	Reported by patients as ranging between none, moderate or severe	1 week
Fever	Temperature of >37.8C	1 week

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: University of British Columbia; McGill University; University of Calgary
• Investigators: Principal Investigator: Dina Kao, MD, University of Alberta

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2019
• Primary Completion (Actual): March 12, 2024
• Study Completion (Actual): March 12, 2024

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 14, 2019
• First Posted (Actual): January 16, 2019

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections
• Other Study ID Numbers: Pro00087406

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No