Clostridia Difficile Colitis, Clostridium Difficile Diarrhea
Conditions
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.
Interventions
BIOLOGICALLyophilized fecal microbiota transplant
15 capsules
BIOLOGICALLyophilized sterile fecal filtrate
15 capsules
Sponsors
University of British Columbia
University of Calgary
McGill University
University of Alberta
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Intervention model description
double blind randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resolution of RCDI | 8 weeks | Proportion of patients without RCDI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resolution of RCDI | 24 weeks | Proportion of patients with sustained cure |
| Serious Adverse Events | 8 weeks | Mortality directly attributable to CDI or treatment |
| Minor Adverse Events | 1 week | Nausea |
| Difficulty swallowing capsules | 1 week | Reported by patients as ranging between none, moderate or severe |
| Fever | 1 week | Temperature of \>37.8C |
Countries
Canada
Outcome results
None listed