Oral Capsule Faecal Microbiota Transplantation for CPE Decolonization

Oral Capsule-administered Faecal Microbiota Transplantation for Intestinal Carbapenemase-producing Enterobacteriaceae Decolonization

Double-blinded, randomised controlled trial to evaluate the clinical efficacy of a single dose of oral capsule-administered faecal microbiota transplantation (FMT) for carbapenemase-producing Enterobacteriaceae (CPE) intestinal decolonisation compared with placebo. Primary outcome is the proportion of patients successfully decolonised of CPE intestinal carriage at 12 weeks after FMT treatment compared with placebo.

Study Overview

• Status: Not yet recruiting
• Conditions: Carbapenem-Resistant Enterobacteriaceae Infection
• Intervention / Treatment: Biological: Oral capsule faecal microbiota transplantation; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Oon Tek Ng, MBBS; Phone Number: +65 6357 7318; Email: Oon_Tek_NG@ttsh.com.sg
• Study Contact Backup: Name: Kalisvar Marimuthu, MBBS; Email: kalisvar_marimuthu@ttsh.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admitted as inpatient at the study site at the time of screening.
• Aged ≥21 years at the time of screening.
• Sufficiently ambulant to return for outpatient clinic study visit.
• Detection of CPE (result reported by clinical microbiology laboratory).
• Ability to provide informed consent.
• Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use at least one method of effective contraception for the duration of the trial.
• Colonisation of the gastrointestinal tract with CPE, confirmed by at least one positive rectal swab taken ≤7 days before randomisation (direct PCR testing using Xpert Carba-R, performed by study team independent of the hospital screening protocol).
• Ability to swallow "safety test" capsule (one test capsule given during pre-randomisation evaluation).
• Antibiotics ceased for at least 48 hours before pre-randomisation evaluation.
• Negative urine pregnancy test for pre-menopausal women taken ≤7 days before randomisation

Exclusion Criteria:

• Presence of acute diarrhoeal illness (e.g. gastroenteritis, C. difficile colitis) or chronic diarrhoeal illness (e.g. irritable bowel syndrome or inflammatory bowel disease, unless they are in remission for at least 3 months prior to enrolment).
• Current use or planned use of an investigational drug within 3 months of enrolment.
• Presence of significant immunosuppression, including but not limited to: use of monoclonal antibody, use of prolonged steroids equivalent to prednisolone dose of ≥20mg/day for ≥28 days, solid organ transplantation, bone marrow transplantation, HIV infection with CD4 count of ≤200, bone marrow transplant, ongoing chemotherapy or radiation therapy, and congenital immunodeficiency.
• Oropharyngeal dysphagia, significant oesophageal dysphagia, or other inability to swallow.
• History of surgery altering gastrointestinal anatomy (e.g. colostomy, colectomy).
• Ileus or small bowel obstruction.
• Risk of aspiration.
• History of gastroparesis.
• Severe food allergy (anaphylaxis or anaphylactoid reaction).
• Adverse event attributable to previous FMT.
• Those who are pregnant or plan to be pregnant within 3 months of enrolment.
• Those who are breastfeeding or plan to breastfeed during the trial.
• Life expectancy <3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Single dose of 30 oral capsules containing FMT from a stool bank	Biological: Oral capsule faecal microbiota transplantation; Single dose of 30 oral capsules containing healthy donor stool from a stool bank
Placebo Comparator: Placebo; Single dose of 30 oral placebo capsules	Other: Placebo; Single dose of 30 oral placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients successfully decolonised of CPE intestinal carriage at 12 weeks.	Decolonisation is determined by the following test outcomes: i. Negative PCR result (CP genes undetected) for rectal swab sample subjected to direct PCR (Xpert Carba-R) ii. Negative PCR result (CP genes undetected) for rectal swab sample subjected to culture on ChromID CARBA SMART media followed by PCR for suspected CPE colonies (Xpert Carba-R) iii. Negative PCR result (CP genes undetected) for stool sample subjected to direct PCR (Xpert Carba-R) iv. Negative PCR result (CP genes undetected) for stool sample subjected to culture on ChromID CARBA SMART media followed by PCR for suspected CPE colonies (Xpert Carba-R) At least two of the four tests must be evaluable (clear positive or negative result obtained). Subject not meeting these criteria will be considered not-decolonised. If any one of the PCR results are positive, the subject is considered not-decolonised.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients successfully decolonised of CPE intestinal carriage at 1, 2, 6, 24, 36 and 48 weeks.	Decolonisation is determined by the following test outcomes: i. Negative PCR result (CP genes undetected) for stool sample subjected to direct PCR (Xpert Carba-R) ii. Negative PCR result (CP genes undetected) for stool sample subjected to culture on ChromID CARBA SMART media followed by PCR for suspected CPE colonies (Xpert Carba-R) At least one of the two tests have to be evaluable (clear positive or negative result obtained). Subject not meeting these criteria will be considered not-decolonised. If any one of the PCR results are positive, the subject is considered not-decolonised.	1, 2, 6, 24, 36 and 48 weeks
Progression to CPE infection	Proportion of patients who progressed to CPE infection within 48 weeks, defined by isolation of CPE in a clinical isolate, compatible with an infective syndrome, as assessed by the study investigators.	Up to 48 weeks
Changes in stool microbiome	Projected output from metagenomics analysis (i and ii) and culture-based assays (iii): i. Comparison of gut microbial composition at 1, 2, 6, 12, 24, 36, and 48 weeks after treatment with FMT or placebo with composition at pre-randomisation (including Shannon Diversity Index) ii. Comparison of relative abundance of CP producing and non-CP producing species at 1, 2, 6, 12, 24, 36, and 48 weeks after treatment with FMT versus placebo iii. CPE load in stool at 1, 2, 6, 12, 24, 36, and 48 weeks post-treatment	1, 2, 6, 12, 24, 36, and 48 weeks
Frequency and severity of adverse events	Comparison of the incidence and severity of all adverse events reported post-randomisation up to 48 weeks between the intervention and placebo groups.	Up to 48 weeks

Collaborators and Investigators

• Sponsor: Tan Tock Seng Hospital
• Collaborators: Singapore Clinical Research Institute
• Investigators: Principal Investigator: Oon Tek Ng, MBBS, Tan Tock Seng Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: February 7, 2021
• First Submitted That Met QC Criteria: February 7, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 9, 2021
• Last Update Submitted That Met QC Criteria: February 7, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections
• Other Study ID Numbers: CSAINV18nov-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No