Antibiotic Resistant Strain
Conditions
Keywords
vancomycin resistant enterococcus, VRE, decolonization, VRE colonization, fecal microbiota transplantation, FMT, FMT capsule, capsule, antimicrobial resistance, antibiotic resistance, MDRO, multidrug-resistant organism, OpenBiome
Brief summary
The objective of this study is to provide preliminary insight into the safety and efficacy of fecal microbiota transplantation (FMT) for the eradication of gastrointestinal carriage of vancomycin-resistant Enterococcus.
Detailed description
Note: The Protocol and Statistical Analysis Plan document contains modifications from what is on file at the FDA to reflect redactions and formatting requirements for public posting on ClinicalTrials.gov.
Interventions
BIOLOGICALEncapsulated fecal microbiota preparation
30 capsules
BIOLOGICALEncapsulated placebo
30 capsules
Sponsors
University of Wisconsin, Madison
Indiana University
Microbiome Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Adults 18 years or older at the time of enrollment. * Able to provide signed and dated informed consent. * Identified as VRE-positive by a stool culture within last 14 days. * Women of childbearing potential in sexual relationships with men must use an acceptable method of contraception§ from 30 days prior to enrollment until 4 weeks after completing study treatment. * Males must agree to avoid impregnation of women during and for four weeks after completing study treatment through use of an acceptable method of contraception\*. * Includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy. * Includes, but is not limited to, barrier with additional spermicidal foam or jelly and vasectomy.
Exclusion criteria
* Female patient who are pregnant, lactating or planning on becoming pregnant during study. Female patients of childbearing potential will undergo a pregnancy test, and be excluded from the study if positive. * Inability (e.g. dysphagia) to or unwilling to swallow capsules. * Active antibiotic resistant bacteria (ARB) or gastrointestinal infection at time of enrollment. * Patient received antibiotics in the last 48 hours. Patients will be eligible to enroll if antibiotic therapy is discontinued for at minimum 48 hours prior to randomization. Does not include antibiotics used for prophylaxis or topical antibiotics. * Requires continued antibiotic use or anticipates antibiotic use in the upcoming 4 weeks. Does not include antibiotics used for prophylaxis or topical antibiotics. * Unwilling to withhold probiotics for a minimum of 48 hours prior to providing a screening stool sample. * Known or suspected toxic megacolon and/or known small bowel ileus. * Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy. * History of total colectomy or bariatric surgery. * Admitted to or expected to an intensive care unit for medical reasons (not just boarding). Patients residing in a nursing home, long-term care facility or rehabilitation center may be enrolled. * Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy. Patients on maintenance chemotherapy may be enrolled only after consultation with medical monitor. * Unable or unwilling to comply with protocol requirements. * Expected life expectancy \< 6 months * Previous FMT or microbiome-based products at any time excluding this study. * Patients with a history of severe anaphylactic or anaphylactoid food allergy. * Solid organ transplant recipients ≤ 90 days post-transplant or on active treatment for rejection. * Neutropenia (≤500 neutrophils/mL) or other severe immunosuppression. Anti-TNF will be permitted. Patients on monoclonal antibodies to B and T cells. glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine, methotrexate), calcineurin inhibitors (tacrolimus, cyclosporine) and mycophenolate mofetil may be enrolled only after consultation with the medical monitor. * If at risk for CMV/EBV associated disease (at investigator's discretion, e.g. immunocompromised), negative IgG testing for cytomegalovirus (CMV) or Epstein Barr Virus (EBV). * A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Adverse Event (AE); Severe Adverse Event (SAE); and Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) | Day 10 (±3 days) after randomization | Percentage of participants with an adverse event (AE); severe adverse event (SAE); and newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI) through Day 10 (± 3 days) after randomization. |
| Percentage of Participants With VRE Decolonization | Day 10 (±3 days) after randomization | VRE decolonization is defined by absence of VRE on stool culture using standard clinical laboratory techniques at Day 10 (± 3 days) after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ARB Infection 4 Weeks Following FMT | Week 4 (±5 days) after randomization | Percentage of participants with composite ARB infection |
| Percentage of Participants With ARB Colonization on Day 10 Following Fecal Microbiota Transplantation (FMT) | Day 10 (± 3 days) after randomization | Percentage of participants with other antibiotic resistant bacteria (ARB) colonization |
| Number of Days Between FMT and VRE Colonization and Infection Occurs | Up to 6 months after randomization | Time (in days) from randomization until the study day when VRE colonization and infection occurs |
| Adverse Events Within 4 Weeks Following FMT | Week 4 (±5 days) after randomization | Percentage of participants with an adverse event (AE) |
| Serious Adverse Events Within 4 Weeks Following FMT | Week 4 (±5 days) after randomization | Percentage of participants with a serious adverse event (SAE) |
| Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) | Week 4 (±5 days) after randomization | Percentage of participants with newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI) |
| Serious Adverse Events Within 6 Months Following FMT | Month 6 (±14 days) phone safety assessment after randomization | Percentage of participants with a Serious Adverse Event (SAE) |
| VRE Decolonization Among Immunocompromised Patients | Day 10 (± 3 days) after randomization | Percentage of participants with VRE decolonization among immunocompromised patients |
| Percentage of Participants With VRE Infection | Week 4 (±5 days) after randomization | Percentage of participants with VRE infection, defined as an associated bacteremia, urinary tract infection, or wound-related infection. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Microbiome Disruption | Day 3, day 10, week 4 after randomization. | To evaluate the microbiome disruption index (MDI) by 16s rRNA sequencing): MDI-community and MDI-species |
| Engraftment Dynamics | 6 months following FMT | To evaluate the trends in VRE type/strain-level engraftment using whole genome sequencing among those colonized |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the listed tertiary academic hospitals from August 15, 2017 to September 30, 2018.
Participants by arm
| Arm | Count |
|---|---|
| Active: Encapsulated Fecal Microbiota Preparation Single dose of oral, encapsulated fecal microbiota preparation (30 capsules per dose) with follow-up at 3 days, 10 days, 28 days, and 6 months. | 4 |
| Placebo: Encapsulated Placebo Single dose of oral, placebo capsule (30 capsules per dose) with follow-up at 3 days, 10 days, 28 days, and 6 months. | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Total | Placebo: Encapsulated Placebo | Active: Encapsulated Fecal Microbiota Preparation |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 3 / 4 | 5 / 5 |
| serious Total, serious adverse events | 2 / 4 | 1 / 5 |
Outcome results
Primary
Percentage of Participants With an Adverse Event (AE); Severe Adverse Event (SAE); and Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI)
Percentage of participants with an adverse event (AE); severe adverse event (SAE); and newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI) through Day 10 (± 3 days) after randomization.
Time frame: Day 10 (±3 days) after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active: Encapsulated Fecal Microbiota Preparation | Percentage of Participants With an Adverse Event (AE); Severe Adverse Event (SAE); and Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) | 3 Participants |
| Placebo: Encapsulated Placebo | Percentage of Participants With an Adverse Event (AE); Severe Adverse Event (SAE); and Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) | 5 Participants |
Primary
Percentage of Participants With VRE Decolonization
VRE decolonization is defined by absence of VRE on stool culture using standard clinical laboratory techniques at Day 10 (± 3 days) after randomization.
Time frame: Day 10 (±3 days) after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active: Encapsulated Fecal Microbiota Preparation | Percentage of Participants With VRE Decolonization | 1 Participants |
| Placebo: Encapsulated Placebo | Percentage of Participants With VRE Decolonization | 1 Participants |
Secondary
Adverse Events Within 4 Weeks Following FMT
Percentage of participants with an adverse event (AE)
Time frame: Week 4 (±5 days) after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active: Encapsulated Fecal Microbiota Preparation | Adverse Events Within 4 Weeks Following FMT | 3 Participants |
| Placebo: Encapsulated Placebo | Adverse Events Within 4 Weeks Following FMT | 5 Participants |
Secondary
Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI)
Percentage of participants with newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI)
Time frame: Week 4 (±5 days) after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active: Encapsulated Fecal Microbiota Preparation | Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) | 0 Participants |
| Placebo: Encapsulated Placebo | Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) | 0 Participants |
Secondary
Number of Days Between FMT and VRE Colonization and Infection Occurs
Time (in days) from randomization until the study day when VRE colonization and infection occurs
Time frame: Up to 6 months after randomization
Population: Data not collected as no participants in the trial were colonized and infected by VRE following randomization.
Secondary
Percentage of Participants With ARB Colonization on Day 10 Following Fecal Microbiota Transplantation (FMT)
Percentage of participants with other antibiotic resistant bacteria (ARB) colonization
Time frame: Day 10 (± 3 days) after randomization
Population: Data not collected as no participants in the trial entered the study colonized with an ARB other than VRE
Secondary
Percentage of Participants With ARB Infection 4 Weeks Following FMT
Percentage of participants with composite ARB infection
Time frame: Week 4 (±5 days) after randomization
Population: Data not collected as no participants in the trial entered the study colonized with an ARB other than VRE
Secondary
Percentage of Participants With VRE Infection
Percentage of participants with VRE infection, defined as an associated bacteremia, urinary tract infection, or wound-related infection.
Time frame: Week 4 (±5 days) after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active: Encapsulated Fecal Microbiota Preparation | Percentage of Participants With VRE Infection | 0 Participants |
| Placebo: Encapsulated Placebo | Percentage of Participants With VRE Infection | 0 Participants |
Secondary
Serious Adverse Events Within 4 Weeks Following FMT
Percentage of participants with a serious adverse event (SAE)
Time frame: Week 4 (±5 days) after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active: Encapsulated Fecal Microbiota Preparation | Serious Adverse Events Within 4 Weeks Following FMT | 0 Participants |
| Placebo: Encapsulated Placebo | Serious Adverse Events Within 4 Weeks Following FMT | 0 Participants |
Secondary
Serious Adverse Events Within 6 Months Following FMT
Percentage of participants with a Serious Adverse Event (SAE)
Time frame: Month 6 (±14 days) phone safety assessment after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active: Encapsulated Fecal Microbiota Preparation | Serious Adverse Events Within 6 Months Following FMT | 2 Participants |
| Placebo: Encapsulated Placebo | Serious Adverse Events Within 6 Months Following FMT | 1 Participants |
Secondary
VRE Decolonization Among Immunocompromised Patients
Percentage of participants with VRE decolonization among immunocompromised patients
Time frame: Day 10 (± 3 days) after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active: Encapsulated Fecal Microbiota Preparation | VRE Decolonization Among Immunocompromised Patients | 1 Participants |
| Placebo: Encapsulated Placebo | VRE Decolonization Among Immunocompromised Patients | 1 Participants |
Other Pre-specified
Engraftment Dynamics
To evaluate the trends in VRE type/strain-level engraftment using whole genome sequencing among those colonized
Time frame: 6 months following FMT
Other Pre-specified
Microbiome Disruption
To evaluate the microbiome disruption index (MDI) by 16s rRNA sequencing): MDI-community and MDI-species
Time frame: Day 3, day 10, week 4 after randomization.