Faecal Microbiota Transplantation to Eradicate Gut Colonisation From Carbapenem-resistant Enterobacteriaceae: a Randomised Controlled Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Number of participants who will obtain an eradication of CRE carriage after treatments
Study Overview
Brief Summary
Rates of antimicrobial resistance are increasing worldwide. There is increasing evidence that physiological gut microbiota is a large reservoir of antibiotic-resistance genes. Healthy gut microbiota is known to prevent the colonization of the gastrointestinal tract by pathogens, the so-called mechanism of colonization resistance, but this protective mechanism can be altered by therapies that impair gut microbiota, including antibiotics or chemotherapeutics, with consequent colonisation of gut pathogens, including multi-drug resistant bacteria (MDRB). MDRB carriers represent an epidemiological threat to other hospitalized patients and to the whole community, but are also at risk of developing clinical consequences of this colonization, including bloodstream infections from these pathogens. Fecal microbiota transplantation (FMT) has shown high efficacy in the eradication of recurrent C. difficile infection, and initial evidence suggests that this procedure could be useful in eradicating also MDRB, mainly carbapenem-resistant Enterobacteriaceae.
However, current evidence is mostly limited to case reports and case series, and to a single randomised trial, which was stopped early and did not draw clear conclusion. In a systematic review of 21 studies and 192 patients, eradication rates ranged from 0% to 100%, and authors concluded that larger, well designed randomised controlled trials are needed to further explore this therapy.
The aim of this study is to investigate the efficacy of FMT, compared with placebo FMT, in eradicating gut colonisation from MDRB, focusing on CRE. The investigators will randomize patients colonized by CRE (diagnosed by rectal swab) to FMT from healthy donors or placebo, by colonoscopy. Then, patients will be followed up, rectal swabs will be repeated, and stool samples for culture and microbiome analysis will be collected, up to 3 months after FMT.
Detailed Description
Rates of antimicrobial resistance are increasing worldwide. There is increasing evidence that physiological gut microbiota is a large reservoir of antibiotic-resistance genes. Healthy gut microbiota is known to prevent the colonization of the gastrointestinal tract by pathogens, the so-called mechanism of colonization resistance, but this protective mechanism can be altered by therapies that impair gut microbiota, including antibiotics or chemotherapeutics, with consequent colonisation of gut pathogens, including multi-drug resistant bacteria (MDRB). MDRB carriers represent an epidemiological threat to other hospitalized patients and to the whole community, but are also at risk of developing clinical consequences of this colonization, including bloodstream infections from these pathogens. Fecal microbiota transplantation (FMT) has shown high efficacy in the eradication of recurrent C. difficile infection, and initial evidence suggests that this procedure could be useful in eradicating also MDRB, mainly carbapenem-resistant Enterobacteriaceae.
However, current evidence is mostly limited to case reports and case series, and to a single randomised trial, which was stopped early and did not draw clear conclusion. In a systematic review of 21 studies and 192 patients, eradication rates ranged from 0% to 100%, and authors concluded that larger, well designed randomised controlled trials are needed to further explore this therapy.
The extended aims of this study are:
- To compare the efficacy of donor FMT and placebo FMT in eradicating gut colonisation from CRE
- To compare the efficacy of donor FMT and placebo FMT in preventing clinical manifestations of gut colonisation from CRE
- To investigate changes in gut microbiome after treatments
The investigators will carry out a single-centre placebo-controlled, double blind randomised clinical trial of donor FMT vs placebo FMT in carriers of CRE Patients will be recruited among those referred to the infectious disease outpatient clinic of the Fondazione Policlinico Universitario "A. Gemelli". Patients with all inclusion criteria and none of the exclusion criteria (detailed in the specific section of this website) will be considered for this study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
To mask treatments to physicisans and recipients, both FMT bottles and syringes will be covered with dark-coloured paper before the infusion, and the patients will be unable to see the endoscopic display during the procedure. Moreover, the physicians who will evsaluate patients at follow-up will not aware of the treatment being administered.
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Donor FMT
Patients enrolled in this arm will receive donor FMT
Intervention: Donor FMT (Biological)
Placebo FMT
Patients enrolled in this arm will receive placebo FMT (that will be made of water)
Intervention: Placebo FMT (Other)
Outcomes
Primary Outcomes
Number of participants who will obtain an eradication of CRE carriage after treatments
Time Frame: 4 weeks
The investigators will evaluate the number of participants who will obtain eradication of CRE carriage after treatments, at 4 weeks-follow-up, evaluated through rectal swab for CRE
Secondary Outcomes
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(12 weeks)
- Number of participants who will obtain an eradication of CRE carriage after treatments(12 weeks)
- Number of participants with significant increase in alpha-diversity and beta-diversity of their gut microbiota after treatments(12 weeks)
Investigators
IANIRO GIANLUCA
Principal Investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS