Fecal Microbiota Transplantation for Early Clostridioides Difficile Infection

Study Overview
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Brief Summary
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Clostridioides difficile (CD) infection (CDI) is a global health threat with an urgent need for new treatment strategies. Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (CDI), and is currently recommended for multiple (three or more), recurrent CDI infections. The role of FMT earlier in the treatment hierarchy of CDI remains to be determined. In this randomized, double-blinded, placebo-controlled clinical trial, we compare FMT with placebo following standard antibiotic treatment for first or second Clostridioides difficile infection.

Detailed Description
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This is a parallel arm placebo-controlled clinical trial. We aim to include 84 adult patients with their first or second episode of Clostridioides difficile (formerly Clostridium difficile) infection. All patients receive vancomycin standard therapy. Patients are randomised in a 1:1 ratio to two treatments with capsules that contain either FMT+FMT or placebo+placebo. The primary outcome is absence of C difficile-associated disease 8 weeks after randomisation. Patients who have fulminant disease where it is deemed unethical to give placebo are offered open-label FMT. The primary outcome in patients with fulminant C difficile infection is 8 weeks mortality.

Official Title
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Fecal Microbiota Transplantation for Early Clostridioides Difficile Infection

Conditions
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Clostridium Difficile Infection, Clostridioides Difficile Infection

Intervention / Treatment
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* Other: Fecal microbiota transplantion (FMT)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. or 2. CDI (within a year) defined as: > 3 bowel movements of Bristol 6-7 per day and positive stool CD-test. Age 18 years or higher. Exclusion Criteria: Pregnancy Does not speak or understand the Danish language Current antibiotic treatment other than vancomycin Current treatment with potential interations with vancomycin Allergy to vancomycin Previous anaphylactic reactions due to food allergies Continuous need for proton pump inhibitor Documented gastroparesis Fulminant CDI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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: Single Group Assignment
Interventional Model Description: Patients are randomized to either vancomycin + 2 FMT or 2 placebo. An open-label arm exists for patients with fulminant CDI.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vancomycin 125 x 4 for 10 days + 2 Fecal Microbota Transplantation<br>Patients are required to undergo full treatment with vancomycin and are randomized following completion to, in this arm, FMT. | Other: Fecal microbiota transplantion (FMT)<br>* Single donor, fecal microbiota transplantion (FMT) from healthy human donors.<br>|
| Placebo Comparator: Vancomycin 125 x 4 for 10 days + 2 Placebo<br>Patients are required to undergo full treatment with vancomycin and are randomized following completion to, in this arm, placebo. | Other: Placebo<br>* Food coloring, water, glycerol<br>|
| Other: Open-label for screened, but not randomized patients with fulminant CDI<br>This arm exists for patients with fulminant CDI and for randomization to placebo may be considered unethical. | Other: Fecal microbiota transplantion (FMT)<br>* Single donor, fecal microbiota transplantion (FMT) from healthy human donors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of CD-associated diarrhea (CDAD) week 8 | Measured as a combined clinical resolution or persistent diarrhea, but with negative CD test. | 8 weeks following treatment | 
| Mortality week 8 | In the open-label arm for patients who cannot be randomized due to ethical reasons, the primary outcome is mortality. | 8 weeks following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of CD-associated diarrhea (CDAD) week 1 | Measured as a combined clinical resolution or persistent diarrhea, but with negative CD test. | 1 week following treatment | 
| Negative CD toxin-test week 1 | Faecal C difficile PCR test | 1 week following treatment | 
| Negative CD toxin-test week 8 | Faecal C difficile PCR test | 8 weeks following treatment | 
| Mortality week 8 | Date of death | 8 weeks | 
| Colectomy rate week 8 | Date of colectomy | 8 weeks | 
| Health-related quality of life | EDQ5D-5L | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal microbiota tranplantation, FMT, CDI