Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection

Study Overview
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Brief Summary
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Randomized open label clinical trial to compare the clinical and microbiological efficacy of fecal microbiota transplantation, fidaxomicin, and vancomycin for relapsing Clostridium difficile infection

Official Title
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Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Other: Fecal microbiota transplantation
* Drug: Fidaxomicin
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Relapse of Clostridium difficile infection with previous trial of vancomycin or fidaxomicin Exclusion Criteria: Pregnancy or breastfeeding Does not speak or understand the Danish language Current antibiotic treatment other than metronidazole, vancomycin, fidaxomicin fulminant colitis which contraindicates medical treatment physician's evaluation that the patient cannot tolerate project inclusion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMT<br>Fecal microbiota transplantation (FMT) following 4-10 days of vancomycin 125 mg x 4, using cryopreserved feces from a healthy anonymous donor | Other: Fecal microbiota transplantation<br>* FMT follows 4-10 days of vancomycin 125 mg x 4 daily<br>|
| Active Comparator: Fidaxomicin<br>10 days fidaxomicin 200 mg x 2 daily | Drug: Fidaxomicin<br>* Fidaxomicin 200 mg x 2 daily for 10 days<br>|
| Active Comparator: Vancomycin<br>10 days vancomycin 125 x 4 daily | Drug: Vancomycin<br>* Vancomycin 125 mg x 4 daily for 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with global resolution (clinical resolution AND negative Clostridium difficile PCR test) 8 weeks after primary treatment | Global resolution is defined as combined clinical and microbiological resolution, without need for rescue FMT or colectomy. Clinical resolution is absence of abdominal pain (pain score 0 (no pain), 1 (mild pain), 2 (moderate pain), 3 (severe pain)) and less than 3 bowel movements of Bristol 5 or lower, per day. Microbiological resolution is negative Clostridium difficile test 8 weeks after finishing allocated treatment | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with clinical resolution 1 week after primary treatment | Clinical resolution (absence of abdominal pain and less than 3 bowel movements of Bristol 5 or lower, per day) 1 week after finishing allocated treatment | 1 week | 
| Number of patients with clinical resolution 8 weeks after primary treatment | Clinical resolution (absence of abdominal pain and less than 3 bowel movements of Bristol 5 or lower, per day) 8 weeks after finishing allocated treatment, without need for rescue FMT or colectomy | 8 weeks | 
| Number of patients with clinical resolution 26 weeks after primary treatment | Clinical resolution (absence of abdominal pain and less than 3 bowel movements of Bristol 5 or lower, per day) 26 weeks after finishing allocated treatment, without need for rescue FMT or colectomy | 26 weeks | 
| Number of patients with microbiological resolution week 1 | Microbiological resolution (negative Clostridium difficile PC test) 1 weeks after finishing allocated treatment, without need for rescue FMT or colectomy | 1 week | 
| Number of patients with microbiological resolution week 8 | Microbiological resolution (negative Clostridium difficile PC test) 8 weeks after finishing allocated treatment, without need for rescue FMT or colectomy | 8 weeks | 
| Number of patients with microbiological resolution week 26 | Microbiological resolution (negative Clostridium difficile PC test) 26 weeks after finishing allocated treatment, without need for rescue FMT or colectomy | 26 weeks | 
| Number of patients with global resolution (Clinical and microbiological resolution) week 1 | Clinical resolution (absence of abdominal pain and less than 3 bowel movements of Bristol 5 or lower, per day) and microbiological resolution(negative Clostridium difficile test) 1 week after finishing allocated treatment, without need for rescue FMT or colectomy | 1 week | 
| Number of patients with global resolution (Clinical and microbiological resolution) week 26 | Clinical resolution (absence of abdominal pain and less than 3 bowel movements of Bristol 5 or lower, per day) and microbiological resolution(negative Clostridium difficile test) 26 weeks after finishing allocated treatment, without need for rescue FMT or colectomy | 26 weeks | 
| Numerical change in quality of life (EQ5D-3L) week 8 and 26 | EQ5D-3L (www.euroqol.com) measures self-reported quality of life in 5 dimensions (each three levels), rendering score from 5 (lowest and best) to 15 (highest and worst) plus an overall reporting of general well being (0, lowest, worst to 100, highest, best). Scoring is obtained week 0,8,26 after randomization. Numerical changes are documented and compared using non-parametric statistics | 8 and 26 weeks | 
| Microbiota pattern changes 1, 8 and 26 weeks | Microbiota profiling, 16S rRNA, absence or presence of specific genera | 1, 8 and 26 weeks |