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
About this trial
This is an interventional treatment trial for Carbapenem-Resistant Enterobacteriaceae Infection
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.
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
NCT ID
NCT04746222
First Posted
February 7, 2021
Last Updated
February 7, 2021
Sponsor
Tan Tock Seng Hospital
Collaborators
Singapore Clinical Research Institute
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
Learn more about this trial
Oral Capsule Faecal Microbiota Transplantation for CPE Decolonization
We'll reach out to this number within 24 hrs