Oral Capsule Faecal Microbiota Transplantation for CPE Decolonization

Phase 2

• Conditions: Carbapenem-Resistant Enterobacteriaceae Infection
• Interventions: Biological: Oral capsule faecal microbiota transplantation; Other: Placebo

• Registration Number: NCT04746222
• Lead Sponsor: Tan Tock Seng Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2021-02
• Study First Submitted: 2021-02-07
• Study First Submitted QC: 2021-02-07
• Last Update Submitted: 2021-02-07
• Study First Posted: 2021-02-09
• Last Update Posted: 2021-02-09
• Study Start: 2021-07
• Primary Completion: 2022-10
• Study Completion: 2023-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 108

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment	Oral capsule faecal microbiota transplantation	Single dose of 30 oral capsules containing FMT from a stool bank
Placebo	Placebo	Single dose of 30 oral placebo capsules

Primary Outcome Measures

Name	Time	Method
Proportion of patients successfully decolonised of CPE intestinal carriage at 12 weeks.	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.

Secondary Outcome Measures

Name	Time	Method
Changes in stool microbiome	1, 2, 6, 12, 24, 36, and 48 weeks	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
Frequency and severity of adverse events	Up to 48 weeks	Comparison of the incidence and severity of all adverse events reported post-randomisation up to 48 weeks between the intervention and placebo groups.
Progression to CPE infection	Up to 48 weeks	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.
Proportion of patients successfully decolonised of CPE intestinal carriage at 1, 2, 6, 24, 36 and 48 weeks.	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.