Clinical trial NCT03806803: Multicentre Blinded Comparison of Lyophilized Sterile Fecal Filtrate to Lyophilized Fecal Microbiota Transplant in Recurrent Clostridioides Difficile Infection
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridia Difficile Colitis
Clostridium Difficile Diarrhea
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: University of British Columbia
name: University of Calgary
name: McGill University
First posted: 2019-01-16
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind randomized
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Resolution of RCDI
timeFrame: 8 weeks
Secondary outcomes:
measure: Resolution of RCDI
timeFrame: 24 weeks
measure: Serious Adverse Events
timeFrame: 8 weeks
measure: Serious Adverse Events
timeFrame: 8 weeks
measure: Minor Adverse Events
timeFrame: 1 week
measure: Minor Adverse Events
timeFrame: 1 week
measure: Minor Adverse Events
timeFrame: 1 week
measure: Difficulty swallowing capsules
timeFrame: 1 week
measure: Fever
timeFrame: 1 week
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Victoria
country: Canada
facility: University of British Columbia
state: British Columbia
city: Montréal
country: Canada
facility: Mcgill University Health Centre
state: Quebec
city: Calgary
country: Canada
facility: University Of Calgary
Study officials:
affiliation: University of Alberta
name: Dina Kao, MD
role: PRINCIPAL_INVESTIGATOR
References: