Ignite Creation Date:
2024-05-06 @ 3:46 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04759001
Status:
UNKNOWN
Last Update Posted:
2021-08-20
First Post:
2021-02-13
Brief Title:
FMT for the Decolonization of Carbapenem-resistant Enterobacteriaceae
Sponsor:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Organization:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study Overview
Official Title:
Faecal Microbiota Transplantation to Eradicate Gut Colonisation From Carbapenem-resistant Enterobacteriaceae a Randomised Controlled Trial
Status:
UNKNOWN
Status Verified Date:
2021-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FMT-CRE
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
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
Before randomisation demographic data will be collected by the infectious disease staff Moreover patients will repeat rectal swab and stool culture
Additionally patients will be requested to give stool samples to be collected in a sterile sealed container and stored at -80C for metagenomic assessment of gut microbiome and meta-transcriptome assessment by the microbiology staff
After baseline assessments patients will be randomly assigned to one of the following treatment arms
Donor FMT D-FMT
Placebo FMT P-FMT
Patients in both groups will undergo a single FMT procedure by colonoscopy Each patient in the donor FMT group will receive faeces from one single donor Placebo FMT will be made of 250 mL water The selection of stool donors will be performed by the gastroenterology staff following protocols previously recommended by international guidelines and according the new recommendation imposed by the reorganisation of faecal microbiota transplant during the COVID-19 pandemic Ianiro et al - Gut 2020 The assignment of faecal infusates from healthy donors to patients will be done randomly without any specific recipient-donor match as this is not recommended by international guidelines All faecal infusates will be manufactured in the microbiology unit of our hospital Only frozen faeces will be used Preparation of frozen faeces will follow protocols from international guidelines
Follow-up visits will be performed by physicians from the gastroenterology and the infectious disease unit All patients will be followed up for 3 months after the end of treatments Follow-up visits will be scheduled at week 1 week 2 week 4 and week 12 after the end of treatments respectively At each visit the following assessments will be performed 1 rectal swab for MDRB 2 collection of stool samples for stool culture 3 collection of stool samples for microbiome analysis 4 record of adverse events Unscheduled follow-up visits will be offered if requested by the patients
Study Outcomes are detailed in the specific section of this website
The statistical analysis will be performed both on an intention-to-treat and per-protocol basis Differences among groups will be assessed with a two-tailed Wilcoxon-rank sum test for continuous data and with Fishers exact probability test using two-tailed P-values for categorical data Differences in cure percentages will be determined with Fishers exact test with two-tailed P values For microbiome analysis statistical differences between group means will be calculated using a two-tailed Wilcoxon-Rank Sum Test through the R statistical software package R Core Team Vienna Austria
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
Before randomisation demographic data will be collected by the infectious disease staff Moreover patients will repeat rectal swab and stool culture
Additionally patients will be requested to give stool samples to be collected in a sterile sealed container and stored at -80C for metagenomic assessment of gut microbiome and meta-transcriptome assessment by the microbiology staff
After baseline assessments patients will be randomly assigned to one of the following treatment arms
Donor FMT D-FMT
Placebo FMT P-FMT
Patients in both groups will undergo a single FMT procedure by colonoscopy Each patient in the donor FMT group will receive faeces from one single donor Placebo FMT will be made of 250 mL water The selection of stool donors will be performed by the gastroenterology staff following protocols previously recommended by international guidelines and according the new recommendation imposed by the reorganisation of faecal microbiota transplant during the COVID-19 pandemic Ianiro et al - Gut 2020 The assignment of faecal infusates from healthy donors to patients will be done randomly without any specific recipient-donor match as this is not recommended by international guidelines All faecal infusates will be manufactured in the microbiology unit of our hospital Only frozen faeces will be used Preparation of frozen faeces will follow protocols from international guidelines
Follow-up visits will be performed by physicians from the gastroenterology and the infectious disease unit All patients will be followed up for 3 months after the end of treatments Follow-up visits will be scheduled at week 1 week 2 week 4 and week 12 after the end of treatments respectively At each visit the following assessments will be performed 1 rectal swab for MDRB 2 collection of stool samples for stool culture 3 collection of stool samples for microbiome analysis 4 record of adverse events Unscheduled follow-up visits will be offered if requested by the patients
Study Outcomes are detailed in the specific section of this website
The statistical analysis will be performed both on an intention-to-treat and per-protocol basis Differences among groups will be assessed with a two-tailed Wilcoxon-rank sum test for continuous data and with Fishers exact probability test using two-tailed P-values for categorical data Differences in cure percentages will be determined with Fishers exact test with two-tailed P values For microbiome analysis statistical differences between group means will be calculated using a two-tailed Wilcoxon-Rank Sum Test through the R statistical software package R Core Team Vienna Austria
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None