FERARO: A prospective, randomised placebo controlled feasibility trial of Faecal microbiota Transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms

INTERVENTION: Product Name: Faecal Microbiota for Transplantation Pharmaceutical Form: Capsule, hard INN or Proposed INN: Faecal Microbiota Other descriptive name: Faecal Microbiota Concentration unit: g gram(s) Concentration type: up to Concentration number: 240‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use CONDITION: Gastrointestinal colonisation and infection with Extended Spectrum Beta‐lactamase (ESBL) producing Enetrobacteriales and Carbapenemase Producing Enetrobacteriales ; MedDRA version: 20.0 Level: LLT Classification code 10004052 Term: Bacterial resistance System Organ Class: 10021881 ‐ Infections and infestations ; MedDRA version: 20.1 Level: PT Classification code 10034133 Term: Pathogen resistance System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] PRIMARY OUTCOME: Main Objective: The primary objective is to determine the feasibility of administering capsulised FMT to participants with the eventual aim of eliminating or reducing stool carriage of MDRGNO as detected by stool culture and PCR for up to 6 months after end of therapy.; ; Primary end point(s): The primary outcome is the consent rate (as a proportion of participants who fulfil inclusion / exclusion criteria). This will be used to determine if a substantive trial is feasible.; ; Secondary Objective: Feasibility; The study will continue to measure how feasible it is to conduct a clinical trial of FMT treatment, by measuring the following:; ; ‐ no. of patients meeting the eligibility criteria for the study ; ‐ no. of patients receiving the treatment; ‐ no.of patients returning for follow up appointments; ‐ no.of patients providing stool samples; ; The ability to recruit enough healthy donors to manufacture the FMT needed for the trial will also be measured. ; ; Efficacy ; The presence of ARB in stool samples provided by patients after receiving FMT or placebo will be measured to see if FMT reduces the amount of bugs in the gut. ; ; Safety and Tolerability ; The proportion of patients experiencing side effects, and any adverse events will be measured. ; ; The secondary objectives will provide the evidence needed to determine how to measure if the treatment works (the primary outcome) in a larger clinical trial, and the number of people needed to take part. Timepoint(s) of evaluation of this end point: The primary outcome is a composite measure which can only be assessed once all patients have had the opportunity to participate, and thus will only be measured at the end of the trial. SECONDARY OUTCOME: Secondary end point(s): The secondary endpoints of the study are to provide preliminary evidence of efficacy for a substantive randomised controlled trial with the purpose of ; choosing the optimal primary outcome estimating the parameters for sample size calculation; ; Secondary outcomes of feasibility are;; Proportion of patients fulfilling inclusion / exclusion criteria; Proportion of patients receiving IMP / placebo (as a % of those consenting); Proportion of patients returning for follow up visits (face to face visit at Day 40); Proportion of patients providing follow up stool samples (Days); Ability to recruit sufficient healthy donors to manufacture all FMT doses to meet demands of this and a future substantive RCT. Assessed by delay in dosing patients (measured in days); ; Additional feasibility assessments will include:; ; Collection of data that may be used in estimating of costs/resources needed to provide FMT in the NHS.; An embedded qualitative study to explore views and experiences of research participants.; ; ; Secondary outcomes of efficacy are;; Gastrointestinal carriage of CRE / ESBL (detected / not detected) by stool culture over time (days 10, 40, 100 and 190); Gastrointestinal carriage of CRE / ESBL (detected / not detected) by multiplex PCR over time (days 10, 40, 100 and 190); ; Secondary outcomes of safety and tolerability are;; proportion of patients experiencing reflux following administration of FMT; Proportion of patients suffering intolerable (resulting in withdrawal from the study) gastrointestinal side effects (including diarrhoea, constipation, abdominal pain, flatulence and bloating). This will be assessed by direct questioning and completion of a short patient questionnaire.; identification of unanticipated harms involved with administration of FMT.; occurrence of any adverse event / serious adverse event; Timepoint(s) of evaluation of this end point: Feasibility assessments will be evaluated at end of trial (additional assessments at month 6 and 12) with the exception of the qualitative study which will be performed during months 6 to 12 of the study.; ; Safety and tolerability assessments will be assessed for each patient following each dosing day (days 1, 2 and 3) and all follow up timepoints (days 10, 40, 100 and 190) as well as any unscheduled participant visits.; INCLUSION CRITERIA: Participant / patient Inclusion criteria • Adult patients (age >18 years or older at time of randomisationconsent) • Current or previous patient at Guy’s and St Thomas’ NHS Foundation Trust • Ability to understand the purpose, potential benefits and risks of the study and capable of giving informed consent. The participant must be able to provide written informed consent. • Documented gastrointestinal carriage of ESBL or CPE (stool sample) in the 21 days prior to consent. • Symptomatic infection with the same target organism of interest in the preceding 6 months Donor Inclusion criteria • Aged between 18 and 60 years of age • Body mass index between 18 and 30 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80