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FMT for MDRO Colonization After Infection in Renal Transplant Recipients (PREMIX)

Primary Purpose

Infection Due to Resistant Organism

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Fecal Microbiota Transplant (FMT)

Bowel preparation

Stool or perirectal swab sampling

Fasting

About this trial

This is an interventional treatment trial for Infection Due to Resistant Organism focused on measuring Carbapenem-resistant Enterobacteriaceae (CRE), Vancomycin-resistant Enterococcus (VRE), Multidrug Resistant Organism (MDRO), Fecal Microbiota Transplant (FMT), Renal Transplant, Colonization, Infection, Antibiotic Resistance, Resistome, Multidrug Resistant (MDR) Pseudomonas

Eligibility Criteria

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

Inclusion Criteria:

Ability to understand and willingness to sign a written informed consent document.
Ability and willingness to comply with study protocol requirements and receive an enema.
History of MDRO infection with at least one of the following target MDROs: CRE, VRE, ESBL, or MDR Pseudomonas.
Prior receipt of a renal transplant.
If applicable, willingness to discontinue probiotics or other microbiota restoration therapies during screening at least seven days prior to study Day 1.
The effects of FMT on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
Negative blood or urine human chorionic gonadotropin (hCG) testing on the day of FMT for WOCBP with documentation of negative test result.
Negative baseline Human Immunodeficiency Virus (HIV) test.
Known serology CMV status confirmed by Medical History (if positive). If no mention of positivity in medical records, serology is tested within 30 days of enrollment for:
- Cytomegalovirus (CMV) by polymerase chain reaction (PCR)
- Cytomegalovirus (CMV), serology Immunoglobulin G (IgG)

Exclusion Criteria:

Female participants who are pregnant, breastfeeding, lactating, or planning a pregnancy during study duration (through 4 weeks after the last dose of investigational product).
Prior gastrointestinal surgery or intervention:
- Ileostomy (in the last 3 months)
- Colostomy (in the last 3 months)
- Gastric or colon resection (in the last 3 months)
- Bariatric surgery (any prior history)
- Total colectomy (any prior history)
Any of the following gastrointestinal conditions:
- Irritable Bowel Syndrome (IBS) with diarrhea in the last 12 months
- Crohn's disease
- Ulcerative Colitis
- Celiac disease
- Untreated in-situ colorectal cancer
- Microscopic colitis
- Toxic megacolon or ileus
- Tube feeding (current or planned)
Known positive stool studies or cultures in the last 30 days for: Ova or parasites, Salmonella, Shigella, Campylobacter
Other enteropathogens - defined as any positive result other than C. difficile on the Biofire FilmArray gastrointestinal panel, (Campylobacter, Plesiomonas, Salmonella, Vibrio, Yersinia, Enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), Shigella, Cryptosporidium, Cyclospora, Entamoeba, Giardia, Adenovirus, Astrovirus, Norovirus, Rotavirus, Sapovirus).
Known uncontrolled intercurrent illness(es) such as, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Acute coronary syndrome
- Cardiac arrhythmia
Any other intercurrent acute illness that in the opinion of the investigator will preclude subject from entering the study
On systemic antibiotics for any reason other than recent MDRO infection. If a potential participant is taking antibiotics for treatment (not prophylaxis) of MDRO infection, then the participant must complete the planned antibiotic course by study Day -2.
Compromised immune system other than transplant immunosuppression:
- HIV-positive as identified by one of the following: Positive HIV test, prior diagnosis of HIV, or active or history of administration of antiretroviral therapy (ART) other than for pre-exposure prophylaxis or post-exposure prophylaxis.
- Known Absolute Neutrophil (ANC) <1000 neutrophils per cubic millimeter (mm^3) in the last 3 months
- Active malignancy requiring intensive induction chemotherapy, radiotherapy, or biologic treatment either concurrently or in the last 2 months
- Acute leukemia
- History of hematopoietic cell transplantation, either allogeneic or autologous in the last 3 years
History of solid organ transplant rejection in the last 6 months
Significant food allergy to foods that are part of the stool donor participant's diet.
Life expectancy is 24 weeks or less.
Any condition that, in the opinion of the investigator, might interfere with study objectives or limit compliance with study requirements, including but not limited to:
- Known active intravenous drug or alcohol abuse
- Psychiatric illness
- Social situation
Participated in an investigational study that also meets one of the following criteria:
- Received an interventional agent (drug, device, or procedure) in the last 28 days
- Enrollment on this study or any other interventional study for MDROs

Sites / Locations

Emory University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Control arm

Fecal Microbiota Transplant (FMT)

Arm Description

The control arm will participate in the bowel preparation and stool or perirectal swab sampling but will not receive Fecal Microbiota Transplant (FMT) nor will they be fasting during their first study cycle (Cycle 0). Participants testing positive for a multi-drug resistant organism at the of Cycle 0 will be eligible to receive microbiota restoration transplant (MRT) for up to two cycles, as necessary (Cycles 1 and 2).

The experimental arm will participate in the bowel preparation, stool or perirectal swab sampling, and will receive Fecal Microbiota Transplant (FMT) using Allogeneic Human Stool in Glycerol 10% (AHSG) on Day 1 of each cycle (Cycles 1 and 2).

Outcomes

Primary Outcome Measures

Number of Adverse Events

The safety and feasibility of using FMT in adult participants with Target MDRO colonization after infection will be measured by comparing the number of adverse events (assessed by CTCAE v4.0) after Day 1 of each cycle as compared to baseline.

Change in Target MDRO Growth

The primary outcome is target MDRO growth on perirectal swab or stool culture on Day 36 of each cycle compared Screening and Day 1 culture results. Participants will be classified as having a complete response, partial response, refractory response or progression based on their Day 36 culture results. Partial response, refractory response, and progression may be collapsed in a non-response category for analytic purposes.

Secondary Outcome Measures

Full Information

NCT ID

NCT02922816

First Posted

September 27, 2016

Last Updated

October 16, 2022

Sponsor

Emory University

Collaborators

Cepheid

1. Study Identification

Unique Protocol Identification Number

NCT02922816

Brief Title

FMT for MDRO Colonization After Infection in Renal Transplant Recipients

Acronym

PREMIX

Official Title

A Pilot Study Using Fecal Microbiota Transplant in Renal Transplant Recipients to Eliminate Multidrug-Resistant Organism Colonization After Infection and Examine Gastrointestinal Carriage in a Randomized Placebo-Controlled Design

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Terminated

Why Stopped

This study was paused and was not resumed due to the COVID-19 pandemic.

Study Start Date

December 1, 2016 (Actual)

Primary Completion Date

December 3, 2021 (Actual)

Study Completion Date

December 3, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

Cepheid

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Transplant patients are at increased risk of colonization and infection with Multidrug Resistant Organisms (MDROs) due to medications that modify their immune systems, increased healthcare and antibiotic exposure, and surgical manipulation of mucosa. In this study, kidney transplant patients who have infections with resistant bacteria will be given a Fecal Microbiota Transplant (FMT), also known as a fecal transplant, after they receive antibiotic treatment. This study will see if FMT will eliminate the resistant bacteria so that the kidney transplant patients do not have to use last resort antibiotics. This Phase 1 pilot study is to obtain preliminary safety data for FMT in renal transplant patients to support the rationale for a subsequent clinical trial, not to establish efficacy or toxicity. This trial is designed to test the safety of FMT, identify clinical outcomes, assess feasibility, and refine the target population in participants with MDRO colonization and intestinal dysbiosis. Data from this study should provide directions for the design of future clinical trials.

Detailed Description

Potential participants who meet key eligibility criteria [adults who have undergone renal transplantation and have a history of infection with the Target Multidrug Resistant Organisms (MDRO)] will be approached for consideration of study participation. For this study, Target MDRO colonization is defined as a positive bacterial culture of either carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant Enterococcus (VRE), Extended Spectrum Beta-Lactamases (ESBL), and/or multidrug resistant (MDR) Pseudomonas from stool or perirectal swab sampling. The 20 trial participants will be randomized in a 1:1 ratio to one of two arms: the control arm [not receiving Allogeneic Human Stool in Glycerol (10%; AHSG) via Fecal Microbiota Transplant (FMT)] and the experimental arm (receiving AHSG via FMT). Participants in the control arm participants can crossover to receive the treatment after completing a study cycle without FMT. Each cycle lasts 6 weeks and participants will complete a maximum of 2 treatment cycles; participants randomized to the experimental arm will complete a maximum of two cycles and those randomized to the control arm will complete up to three cycles. Upon completion of the final cycle, all trial participants will be followed for just over 6 months. In addition to the trial participants, there will also be one stool donor participant. The consented, screened, and eligible stool donor will be identified from an established group of stool donors and will undergo screening procedures that are specific to this study. This individual will donate human stool for the preparation of the AHSG (known as the investigational new drug (IND) product for this study). Upon processing of AHSG, the stool donor will enter the Follow-Up Period and remain available for communication to the study team (if necessary) until the Study Completion Date. However, no scheduled study assessments are required of the stool donor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infection Due to Resistant Organism

Keywords

Carbapenem-resistant Enterobacteriaceae (CRE), Vancomycin-resistant Enterococcus (VRE), Multidrug Resistant Organism (MDRO), Fecal Microbiota Transplant (FMT), Renal Transplant, Colonization, Infection, Antibiotic Resistance, Resistome, Multidrug Resistant (MDR) Pseudomonas

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control arm

Arm Type

Placebo Comparator

Arm Description

Arm Title

Fecal Microbiota Transplant (FMT)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Fecal Microbiota Transplant (FMT)

Intervention Description

The Fecal Microbiota Transplant (FMT) using Allogeneic human stool in glycerol (10%) (AHSG) intervention will be administered via rectal retention enema and performed in either an inpatient or outpatient clinic.

Intervention Type

Procedure

Intervention Name(s)

Bowel preparation

Intervention Description

Trial participants will undergo the bowel preparation by taking magnesium citrate the day before the cycle begins (Day -1).

Intervention Type

Procedure

Intervention Name(s)

Stool or perirectal swab sampling

Intervention Description

Stool or perirectal swabs will be collected at screening (for eligibility determination) and Days 1, 2, 15, and 36 of each cycle.

Intervention Type

Other

Intervention Name(s)

Fasting

Intervention Description

In Cycle 1 and Cycle 2, participants cannot consume food, alcohol, or other liquids on Day 1 prior to the intervention. Trial participants will not be fasting on Day 1 of Cycle 0.

Primary Outcome Measure Information:

Title

Number of Adverse Events

Description

Time Frame

Up to 30 weeks

Title

Change in Target MDRO Growth

Description

Time Frame

Day 1, Up to 30 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ability to understand and willingness to sign a written informed consent document. Ability and willingness to comply with study protocol requirements and receive an enema. History of MDRO infection with at least one of the following target MDROs: CRE, VRE, ESBL, or MDR Pseudomonas. Prior receipt of a renal transplant. If applicable, willingness to discontinue probiotics or other microbiota restoration therapies during screening at least seven days prior to study Day 1. The effects of FMT on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Negative blood or urine human chorionic gonadotropin (hCG) testing on the day of FMT for WOCBP with documentation of negative test result. Negative baseline Human Immunodeficiency Virus (HIV) test. Known serology CMV status confirmed by Medical History (if positive). If no mention of positivity in medical records, serology is tested within 30 days of enrollment for: Cytomegalovirus (CMV) by polymerase chain reaction (PCR) Cytomegalovirus (CMV), serology Immunoglobulin G (IgG) Exclusion Criteria: Female participants who are pregnant, breastfeeding, lactating, or planning a pregnancy during study duration (through 4 weeks after the last dose of investigational product). Prior gastrointestinal surgery or intervention: Ileostomy (in the last 3 months) Colostomy (in the last 3 months) Gastric or colon resection (in the last 3 months) Bariatric surgery (any prior history) Total colectomy (any prior history) Any of the following gastrointestinal conditions: Irritable Bowel Syndrome (IBS) with diarrhea in the last 12 months Crohn's disease Ulcerative Colitis Celiac disease Untreated in-situ colorectal cancer Microscopic colitis Toxic megacolon or ileus Tube feeding (current or planned) Known positive stool studies or cultures in the last 30 days for: Ova or parasites, Salmonella, Shigella, Campylobacter Other enteropathogens - defined as any positive result other than C. difficile on the Biofire FilmArray gastrointestinal panel, (Campylobacter, Plesiomonas, Salmonella, Vibrio, Yersinia, Enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), Shigella, Cryptosporidium, Cyclospora, Entamoeba, Giardia, Adenovirus, Astrovirus, Norovirus, Rotavirus, Sapovirus). Known uncontrolled intercurrent illness(es) such as, but not limited to: Ongoing or active infection Symptomatic congestive heart failure Acute coronary syndrome Cardiac arrhythmia Any other intercurrent acute illness that in the opinion of the investigator will preclude subject from entering the study On systemic antibiotics for any reason other than recent MDRO infection. If a potential participant is taking antibiotics for treatment (not prophylaxis) of MDRO infection, then the participant must complete the planned antibiotic course by study Day -2. Compromised immune system other than transplant immunosuppression: HIV-positive as identified by one of the following: Positive HIV test, prior diagnosis of HIV, or active or history of administration of antiretroviral therapy (ART) other than for pre-exposure prophylaxis or post-exposure prophylaxis. Known Absolute Neutrophil (ANC) <1000 neutrophils per cubic millimeter (mm^3) in the last 3 months Active malignancy requiring intensive induction chemotherapy, radiotherapy, or biologic treatment either concurrently or in the last 2 months Acute leukemia History of hematopoietic cell transplantation, either allogeneic or autologous in the last 3 years History of solid organ transplant rejection in the last 6 months Significant food allergy to foods that are part of the stool donor participant's diet. Life expectancy is 24 weeks or less. Any condition that, in the opinion of the investigator, might interfere with study objectives or limit compliance with study requirements, including but not limited to: Known active intravenous drug or alcohol abuse Psychiatric illness Social situation Participated in an investigational study that also meets one of the following criteria: Received an interventional agent (drug, device, or procedure) in the last 28 days Enrollment on this study or any other interventional study for MDROs

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Colleen S Kraft, MD, MSc

Organizational Affiliation

Emory University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Emory University Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30324

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified sequencing data may be made available to outside collaborators upon request and approval by study team.

IPD Sharing Access Criteria

Researchers interested in using data collected in this study should submit a methodologically sound protocol to the study PI.

Citations:

PubMed Identifier

33029623

Citation

Woodworth MH, Kwon JH, Kraft CS. An Ounce of Prevention Is Equivalent to How Much Decolonization Exactly? Clin Infect Dis. 2021 Jun 1;72(11):e924. doi: 10.1093/cid/ciaa1524. No abstract available.

Results Reference

derived

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FMT for MDRO Colonization After Infection in Renal Transplant Recipients

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