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Oral Capsule Faecal Microbiota Transplantation for CPE Decolonization

Primary Purpose

Carbapenem-Resistant Enterobacteriaceae Infection

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Oral capsule faecal microbiota transplantation
Placebo
Sponsored by
Tan Tock Seng Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carbapenem-Resistant Enterobacteriaceae Infection

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Treatment

    Placebo

    Arm Description

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

    Single dose of 30 oral placebo capsules

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    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
    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.

    Full Information

    First Posted
    February 7, 2021
    Last Updated
    February 7, 2021
    Sponsor
    Tan Tock Seng Hospital
    Collaborators
    Singapore Clinical Research Institute
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04746222
    Brief Title
    Oral Capsule Faecal Microbiota Transplantation for CPE Decolonization
    Official Title
    Oral Capsule-administered Faecal Microbiota Transplantation for Intestinal Carbapenemase-producing Enterobacteriaceae Decolonization
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2021
    Overall Recruitment Status
    Unknown status
    Study Start Date
    July 2021 (Anticipated)
    Primary Completion Date
    October 2022 (Anticipated)
    Study Completion Date
    July 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Tan Tock Seng Hospital
    Collaborators
    Singapore Clinical Research Institute

    4. Oversight

    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
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Carbapenem-Resistant Enterobacteriaceae Infection

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Double-blinded, randomised controlled trial to evaluate the clinical efficacy of oral capsule administered FMT for CPE-intestinal decolonisation compared with placebo (1:1)
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    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.
    Allocation
    Randomized
    Enrollment
    108 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment
    Arm Type
    Experimental
    Arm Description
    Single dose of 30 oral capsules containing FMT from a stool bank
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Single dose of 30 oral placebo capsules
    Intervention Type
    Biological
    Intervention Name(s)
    Oral capsule faecal microbiota transplantation
    Intervention Description
    Single dose of 30 oral capsules containing healthy donor stool from a stool bank
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    Single dose of 30 oral placebo capsules
    Primary Outcome Measure Information:
    Title
    Proportion of patients successfully decolonised of CPE intestinal carriage at 12 weeks.
    Description
    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.
    Time Frame
    12 weeks
    Secondary Outcome Measure Information:
    Title
    Proportion of patients successfully decolonised of CPE intestinal carriage at 1, 2, 6, 24, 36 and 48 weeks.
    Description
    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.
    Time Frame
    1, 2, 6, 24, 36 and 48 weeks
    Title
    Progression to CPE infection
    Description
    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.
    Time Frame
    Up to 48 weeks
    Title
    Changes in stool microbiome
    Description
    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
    Time Frame
    1, 2, 6, 12, 24, 36, and 48 weeks
    Title
    Frequency and severity of adverse events
    Description
    Comparison of the incidence and severity of all adverse events reported post-randomisation up to 48 weeks between the intervention and placebo groups.
    Time Frame
    Up to 48 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    21 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Oon Tek Ng, MBBS
    Phone
    +65 6357 7318
    Email
    Oon_Tek_NG@ttsh.com.sg
    First Name & Middle Initial & Last Name or Official Title & Degree
    Kalisvar Marimuthu, MBBS
    Email
    kalisvar_marimuthu@ttsh.com.sg
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Oon Tek Ng, MBBS
    Organizational Affiliation
    Tan Tock Seng Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Oral Capsule Faecal Microbiota Transplantation for CPE Decolonization

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