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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Clostridia Difficile Colitis, Clostridium Difficile Diarrhea

Intervention / Treatment
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* Biological: Lyophilized fecal microbiota transplant
* Biological: Lyophilized sterile fecal filtrate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double blind randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LFMT<br>Lyophilized fecal microbiota transplant capsules | Biological: Lyophilized fecal microbiota transplant<br>* 15 capsules<br>|
| Experimental: LSFF<br>Lyophilized sterile fecal filtrate capsules | Biological: Lyophilized sterile fecal filtrate<br>* 15 capsules<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| Resolution of RCDI | Proportion of patients with sustained cure | 24 weeks | 
| Serious Adverse Events | Mortality directly attributable to CDI or treatment | 8 weeks | 
| Serious Adverse Events | Infection directly attributable to treatment | 8 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 |