Antibiotic Resistant Strain
Conditions
Keywords
Autologous Fecal Microbiota Transplantation
Brief summary
This study, a Randomized controlled trial of Autologous microbiome reconstitution to prevent Colonization by antibiotic rEsistant bacteria (RACE), seeks to investigate the safety, feasibility and the role of autologous fecal microbiota transplantation (FMT) for the prevention of antibiotic resistant bacteria (ARB) through microbiome restoration.
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
BIOLOGICALAutologous fecal microbiota transplant (Auto-FMP Enema)
FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation.
OTHERPlacebo Enema Preparation
The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms.
Sponsors
Boston Medical Center
Microbiome Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for study enrollment 1. Long-term care residents associated with Boston University-Boston Medical Center nursing home consortium 2. Adults (18 years or older) Inclusion criteria for randomization 1\) Infection requiring antimicrobial treatment at the discretion of the treating physician
Exclusion criteria
for study enrollment 1. Pregnant. Participants of childbearing age will undergo urine pregnancy testing 2. Participant or substitute decision maker unable to provide informed consent 3. Allergies to following ingredients generally recognized as safe: glycerol and sodium chloride 4. Current enrollment in hospice 5. Colostomy 6. Unable to adhere to protocol requirements 7. Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines puts the participant at greater risk from FMT 8. Recent travel (last six months) to high risk regions based on the International SOS Medical Risk Rating system 9. Recent exposure (last six months) to unsafe drinking water
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (NIH Grade ≥2) at Day 7 After Randomization | Day 7 after randomization | Number of participants with NIH Grade ≥2 adverse events at Day 7 after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Clearance of Antibiotic Resistant Bacteria (ARB) | Day 28 after randomization | Number of patients with clearance of ARB among patients colonized at Day 28 by Polymerase Chain Reaction (PCR) assay or culture-based assay. ARBs are: Carbapenem-resistant Enterobacteriaceae (CRE) by PCR or culture assay, Extended spectrum beta-lactamase (ESBL)-producing organisms by PCR or culture assay, Vancomycin-resistant enterococci (VRE) by PCR or culture assay, or Clostridium difficile by PCR |
| Number of Participants Who Develop Any ARB-associated Infections | Day 3, Day 7, Day 28, Month 6 | Number of participants who develop any ARB-associated infections following autologous FMT at Day 3, Day 7, Day 28, and Month 6 |
| Number of Participants With NIH Grade ≥2 AEs at Day 28 and Month 6 | Day 28, Month 6 | Number of participants with NIH Grade ≥2 adverse events (intermediate at Day 28 and long-term at Month 6) following autologous FMT. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Microbiome Disruption Indices (MDI) (16S rRNA Sequencing) | Day 0, Day 3, Day 7, Day 28 | MDI-community and MDI-species at baseline (pre-infection on the date of stool collection), post-antibiotics on the intervention/placebo date (Day 0, Day 3, Day 7, and Day 28) |
Countries
United States
Participant flow
Recruitment details
We enrolled 78 patients across four nursing homes from July 10, 2017 to June 30, 2018. Of these 78, a total of 33 individuals were able to provide a stool sample of sufficient quantity to undergo procedures required for preparation of autologous FMT. As specified in the protocol, only participants that had stool processed into autologous FMT and subsequently received a course of antibiotics will undergo randomization. Out of the 33 eligible participants, a total of 7 were ultimately randomized
Pre-assignment details
Of the 7 randomized participants, 3 participants withdrew prior to administration of FMT. A total of 26 enrolled participants were withdrawn or discontinued prior to randomization for reasons including: enrollment in hospice care, passing away from age-related comorbidities, withdrawal of consent, and non-compliance. The remaining 45 enrolled participants were removed at study closure since they did not meet criteria for randomization at the time of closure.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Autologous Fecal Microbiota Preparation) Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months.
Route of Administration: Enema Dosing Regimen: 125mL x 1 dose
Autologous fecal microbiota transplant (Auto-FMP Enema): FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation. | 4 |
| Placebo Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms.
Placebo Enema Preparation: The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. | 3 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Treatment (Autologous Fecal Microbiota Preparation) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 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 | 2 Participants | 2 Participants | 4 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 | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 4 participants | 3 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 0 / 0 |
| other Total, other adverse events | 2 / 4 | 0 / 0 |
| serious Total, serious adverse events | 4 / 4 | 0 / 0 |
Outcome results
Primary
Number of Participants With Adverse Events (NIH Grade ≥2) at Day 7 After Randomization
Number of participants with NIH Grade ≥2 adverse events at Day 7 after randomization.
Time frame: Day 7 after randomization
Population: All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Autologous Fecal Microbiota Preparation) | Number of Participants With Adverse Events (NIH Grade ≥2) at Day 7 After Randomization | 4 Participants |
| Placebo | Number of Participants With Adverse Events (NIH Grade ≥2) at Day 7 After Randomization | 0 Participants |
Secondary
Number of Participants Who Develop Any ARB-associated Infections
Number of participants who develop any ARB-associated infections following autologous FMT at Day 3, Day 7, Day 28, and Month 6
Time frame: Day 3, Day 7, Day 28, Month 6
Population: All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Autologous Fecal Microbiota Preparation) | Number of Participants Who Develop Any ARB-associated Infections | 0 Participants |
| Placebo | Number of Participants Who Develop Any ARB-associated Infections | 0 Participants |
Secondary
Number of Participants With NIH Grade ≥2 AEs at Day 28 and Month 6
Number of participants with NIH Grade ≥2 adverse events (intermediate at Day 28 and long-term at Month 6) following autologous FMT.
Time frame: Day 28, Month 6
Population: All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention. Note: the 1 participant who experienced Grade ≥2 adverse events experienced a total of two (2) adverse events by Month 6.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Autologous Fecal Microbiota Preparation) | Number of Participants With NIH Grade ≥2 AEs at Day 28 and Month 6 | 1 Participants |
| Placebo | Number of Participants With NIH Grade ≥2 AEs at Day 28 and Month 6 | 0 Participants |
Secondary
Number of Patients With Clearance of Antibiotic Resistant Bacteria (ARB)
Number of patients with clearance of ARB among patients colonized at Day 28 by Polymerase Chain Reaction (PCR) assay or culture-based assay. ARBs are: Carbapenem-resistant Enterobacteriaceae (CRE) by PCR or culture assay, Extended spectrum beta-lactamase (ESBL)-producing organisms by PCR or culture assay, Vancomycin-resistant enterococci (VRE) by PCR or culture assay, or Clostridium difficile by PCR
Time frame: Day 28 after randomization
Population: All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Autologous Fecal Microbiota Preparation) | Number of Patients With Clearance of Antibiotic Resistant Bacteria (ARB) | 0 Participants |
| Placebo | Number of Patients With Clearance of Antibiotic Resistant Bacteria (ARB) | 0 Participants |
Other Pre-specified
Microbiome Disruption Indices (MDI) (16S rRNA Sequencing)
MDI-community and MDI-species at baseline (pre-infection on the date of stool collection), post-antibiotics on the intervention/placebo date (Day 0, Day 3, Day 7, and Day 28)
Time frame: Day 0, Day 3, Day 7, Day 28