The Effect of Faecal Microbiota Transplantation (FMT) on Eradication of Multidrug Resistant Organisms (MRO) in Intestinal Carriers

Study Overview
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Brief Summary
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The aim of this study is to investigate the effect of faecal microbiota transplantation (FMT) on eradication of multidrug resistant organisms (MRO) in the intestine. Ultimately, it would be possible to prevent invasive infections with MRO that are difficult to treat and require last-resort antibiotics. The investigators hypothesize that FMT induce intestinal resistance towards colonization with MRO e.g. Vancomycin resistant Enterococcus Faecium (VRE), carbapenemase-producing Enterobacterales (CPE) and extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E).

Detailed Description
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The study is designed as a randomized, double-blinded and placebo-controlled clinical trial. The participants (n = 80) will be randomized 1:1 to FMT or placebo. FMT or placebo consist of 25-30 capsules which need to be consumed on one day or alternatively consumed over three consecutive days, if one day is unacceptable to the participant. At baseline, eight weeks, and 16 weeks rectal swabs for PCR and culture will be taken. Regarding VRE and CPO, there are specific PCRs followed by confirmatory culture, whereas ESBL-E is detected by culture of rectal swab. Furthermore, participants will be asked to deliver faecal samples as well at baseline and 16 weeks post FMT to examine changes in the intestinal microbiome.

Official Title
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The Effect of Faecal Microbiota Transplantation (FMT) on Eradication of Multidrug Resistant Organisms (MRO) in Intestinal Carriers - a Multicentre, Randomized, Double-blinded and Placebo-controlled Study

Conditions
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Multidrug Resistant Organisms, Faecal Microbiota Transplantation

Intervention / Treatment
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* Other: Faecal microbiota transplantation
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: minimum 18 years Positive rectal PCR and/or culture for MRO Ability to speak and understand Danish or English Capable of swallowing the capsules Exclusion Criteria: Current invasive infection with an MRO e.g. in abdomen, bloodstream or symptomatic urinary tract infection. Severe immune deficiency (defined as current chemo treatment or neurofilocytes < 1000/mm3 Pancreatitis, defined by pancreatic amylases above the upper reference limit Planned or recent abdominal surgery (within 14 days) Parenteral nutrition Current antibiotic treatment of the same MRO as intestinal carriage Terminal disease with expected survival under three months Sepsis defined according to Surviving Sepsis Campaign guidelines Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 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: Randomized.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMT (faecal microbiota transplantation)<br>25-30 capsules of faecal material. | Other: Faecal microbiota transplantation<br>* 25-30 capsules of faecal material<br>|
| Placebo Comparator: Placebo<br>25-30 placebo capsules. | Other: Placebo<br>* 25-30 placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with MRO clearance | Number of participants with MRO clearance after eight weeks. This will be measured on rectal samples that will undergo PCR/culture for ESBL, VRE and CPO. The results from the test will be positive or negative. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with MRO clearance | Number of participants with negative PCR for MRO on rectal swab and faecal culture negative for MRO after 16 weeks. This will be measured on rectal samples that will undergo PCR/culture for ESBL, VRE and CPO. The result from the test will be positive or negative | 16 weeks | 
| Number of participants with adverse events. | Number of participants with adverse events both severe and non-severe. | 8 weeks, 16 weeks and 6 months. | 
| Comparison of the frequency of invasive infections | Comparison of the frequency of invasive infections with the same MRO as the intestinal carriage between the FMT and the placebo group. | 6 months | 
| Comparison of mortality rates, frequency of hospitalization and isolation between the FMT and the placebo group. | Comparison of mortality rates, frequency of hospitalization and isolation between the FMT and the placebo group. | 6 months | 
| Comparison of changes in the diversity of the intestinal microbiome between the FMT group and the placebo group. | Comparison of changes in the diversity of the intestinal microbiome between the FMT group and the placebo group. | 8 weeks and 16 weeks |