Fecal Filtrate as a Treatment Option of Multiple Recurrent Clostridioides Difficile Infection

Study Overview
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Brief Summary
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Clostridioides difficile infection (CDI) is one of the most common hospital-acquired infectious diseases with a high mortality rate (6-30%). The treatment of CDI, especially the recurrent form of the disease is still considered a challenge. The FILTRATE randomized controlled trial aims to investigate the safety and efficacy of fecal filtrate transplantation in the treatment of recurrent CDI and compare it with conventional fecal microbiota transplantation (FMT).

Detailed Description
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The treatment of recurrent CDI is still a burden on the healthcare system. FMT is highly effective for the treatment of recurrent CDI, resulting in the resolution of CDI up to 100% of the cases. FMT also has a good short-term safety profile, however long-term events like transfer of multiresistant bacteria and other living microorganism is still a major problem. On the other hand, the fecal filtrate contains only bacterial debris, proteins, and antimicrobial compounds and not intact microorganisms. The FILTRATE trial is a multicenter, two-arm randomized controlled trial, and aims to compare the safety and efficacy of fecal filtrate transplantation to conventional fecal microbiota transplantation (FMT) in the treatment of recurrent CDI. Adult patients with multiple recurrent (>1) CDIs will be randomized 1:1 to receive either FMT or fecal filtrate transplantation. The transplantation will be carried out using lyophilized capsule on each arm. The primary endpoint of the study will be the clinical resolution of CDI-associated diarrhea 8 weeks after the interventions. Questionnaires will be completed on enrollment and at the time of each follow-up. Adverse events will be recorded and reported to the relevant institutional and national ethics committee. After the intervention, a one-year follow-up is also planned. Blood and stool samples will be collected at baseline and at each follow-up.

Official Title
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Fecal Filtrate Versus Conventional Microbiota Transplantation in the Treatment of Multiple Recurrent Clostridioides Difficile Infection (FILTRATE): A Protocol of a Randomized, Controlled Trial

Conditions
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Clostridium Difficile Infection, Recurrent Clostridium Difficile Infection

Intervention / Treatment
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* Biological: Fecal filtrate transplantation
* Biological: Conventional fecal microbiota transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥18 years multiple recurrent CDI (≥2 previous episodes of CDI) at least 3 or more loose or watery stools (Bristol 5-7) per day a positive Glutamate Dehydrogenase (GDH)-enzyme and positive CDI toxin A and/or B test the patient or the legal guardian sign the written informed consent Exclusion Criteria: pregnancy or breastfeeding ongoing antibiotic treatment fulminant CDI previous FMT immunodeficiency need of intensive care requirement for vasoactive drugs other cause of diarrhea inflammatory bowel diseases irritable bowel syndrome life expectancy shorter than 3 months unavailable for follow-up visits

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fecal filtrate transplantation<br>Patients randomized to the fecal filtrate transplantation group | Biological: Fecal filtrate transplantation<br>* Patients will receive 5-8 encapsulated lyophilized fecal filtrate transplantations in enterosolvent, size 0 capsules. Before intervention patients will receive proton pump inhibitors and prokinetics. After the preparation, the participants will be instructed to swallow the capsules one by one within 5 minutes with fluid to help to swallow the capsules.<br>|
| Active Comparator: Conventional fecal microbiota transplantation<br>Patients randomized to the conventional fecal microbiota transplantation group | Biological: Conventional fecal microbiota transplantation<br>* Patients will receive 5-8 encapsulated lyophilized conventional fecal microbiota transplantations in enterosolvent, size 0 capsules. Before intervention patients will receive proton pump inhibitors and prokinetics. After the preparation, the participants will be instructed to swallow the capsules one by one within 5 minutes with fluid to help to swallow the capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of diarrhea | Clinical resolution of the CDI associated diarrhea, defined by 2 or less stools (Bristol 1-4) per day in two consecutive days. The rate of the outcome will be compared within groups. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of diarrhea | Clinical resolution of the CDI associated diarrhea, defined by 2 or less stools (Bristol 1-4) per day in two consecutive days. The rate of the outcome will be compared within groups. | 1 year | 
| Recurrence of CDI symptoms | Recurrence of the CDI symptoms (diarrhea, abdominal pain ect.) within 8 weeks after an initial amelioration. The rate of the outcome will be compared within groups. | 8 weeks, 1 year | 
| Overall mortality | Overall mortality. The rate of the outcome will be compared within groups. | 8 weeks, 1 year | 
| Disease associated mortality | Disease-associated mortality. The rate of the outcome will be compared within groups. | 8 weeks, 1 year | 
| Adverse events | Proportion of adverse events (AE) and serious adverse events (SAE). The rate of the outcome will be compared within groups. | 8 weeks, 1 year | 
| Change of the intestinal microbiome | Change of the intestinal microbiome at the end of the follow up period regarding to the initial intestinal microbiome. The rate of the outcome will be compared within groups. | 8 weeks, 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fecal microbiota transplantation, fecal filtrate, recurrent infection