Oral Capsule Faecal Microbiota Transplantation for CPE Decolonization

NCT04746222 | Unknown Phase 2 DMC

• 1 other identifier: CSAINV18nov-006
• Study Type: interventional
• Target: 108
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Carbapenem-Resistant Enterobacteriaceae Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• Progression to CPE infection

  Up to 48 weeks

• Changes in stool microbiome

  1, 2, 6, 12, 24, 36, and 48 weeks

• Frequency and severity of adverse events

  Up to 48 weeks

Study Arms (2)

Treatment

EXPERIMENTAL

Single dose of 30 oral capsules containing FMT from a stool bank

Biological: Oral capsule faecal microbiota transplantation

Placebo

PLACEBO COMPARATOR

Single dose of 30 oral placebo capsules

Other: Placebo

Interventions

Oral capsule faecal microbiota transplantation BIOLOGICAL

Single dose of 30 oral capsules containing healthy donor stool from a stool bank

Treatment

Placebo OTHER

Single dose of 30 oral placebo capsules

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tan Tock Seng Hospital: lead
• Singapore Clinical Research Institute: collaborator

MeSH Terms

Interventions

Fecal Microbiota Transplantation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Oon Tek Ng, MBBS

  Tan Tock Seng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oon Tek Ng, MBBS

CONTACT

+65 6357 7318; Oon_Tek_NG@ttsh.com.sg

Kalisvar Marimuthu, MBBS

CONTACT

kalisvar_marimuthu@ttsh.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study subjects will be randomised to either FMT-capsules or placebo (subject and investigator-blinded) immediately prior to capsule administration. Subjects who are randomised to FMT by capsule will receive 30 FMT-containing capsules under direct-observed therapy. Subjects who are randomised to placebo capsules will receive 30 placebo capsules under direct-observed therapy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blinded, randomised controlled trial to evaluate the clinical efficacy of oral capsule administered FMT for CPE-intestinal decolonisation compared with placebo (1:1)

Study Record Dates

• First Submitted: February 7, 2021
• First Posted: February 9, 2021
• Study Start: July 1, 2021
• Primary Completion: October 1, 2022
• Study Completion: July 1, 2023
• Last Updated: February 9, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share