Washington University in St. Louis

PMT for MDRO Decolonization

Purpose

This is a randomized, open label, comparative Phase II trial being conducted to determine whether fecal microbiota transplant using Penn Microbiome Therapy (PMT) products helps standard therapy eradicate antibiotic-resistant bacteria.

Conditions

Multidrug Resistant Bacterial Infection
Enterobacteriaceae Infections
Pseudomonas Aeruginosa
VRE Infection
Methicillin-resistant Staphylococcus Aureus

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Multidrug-resistant organism (MDRO) infection of the bloodstream, respiratory tract, or urinary tract. Qualifying MDROs include extended-spectrum cephalosporin-resistant Enterobacterales (ESCRE) or carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa non-susceptible to two or more classes of antibiotics (MDR-PA), vancomycin-resistant Enterococcus (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). 2. On appropriate antibiotic treatment per clinical phenotypic susceptibility testing of the qualifying MDRO, and with a qualifying antibiotic class. Qualifying antibiotic classes include beta-lactam + beta-lactamase inhibitor, carbapenem (with or without betalactamase inhibitor), fluoroquinolone, lipopeptide, glycopeptide, or oxazolidinone. 3. Expected duration of inpatient antibiotic treatment for index MDRO infection at least 5 days total. 4. At least two calendar days remaining, and no more than 7 calendar days remaining prior to SCAIM (scheduled completion of inpatient appropriate antibiotics for the index MDRO infection). 5. Age ≥ 18 years.

Exclusion Criteria

Evidence of colon/small bowel perforation at the time of study screening. 2. Unable to tolerate enteral and enema nutrition and medication administration (i.e., only able to tolerate intravenous nutrition and medications). 3. Goals of care are directed to comfort rather than curative measures. 4. Moderate or severe neutropenia within 10 calendar days prior to enrollment. 5. Known food allergy that could lead to anaphylaxis. 6. Known allergy to fecal microbiota transplant products or their components 7. Pregnancy or lactation 1. For subjects of childbearing potential (ages 18 to 55) and who are randomized to receive the intervention, the subject must have a negative pregnancy test within 24 hours prior to product administration 2. Female or male subjects (ages 18 to 55) of reproductive potential engaged in active sexual activity that could lead to a pregnancy must agree to use one of the following forms of birth control while receiving study medications and through day 28 following completion of treatment, at minimum: i. Male or female condoms ii. Diaphragm or cervical cap with spermicide, if available iii. Intrauterine device (IUD) iv. Oral contraceptives or other hormonal contraception 8. Known gastrointestinal disease that could affect the safety of fecal microbiota transplant at time of enrollment: 1. Inflammatory Bowel Disease (IBD) 2. Short Gut Syndrome 3. Fistulas 4. Bowel resection surgery 5. Colitis

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, open label, comparative
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental ESCRE/CRE BL-BLI	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention ESCRE/CRE BL-BLI standard of care (SOC)	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
Experimental ESCRE/CRE carbapenem +/- BLI	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention ESCRE/CRE carbapenem +/- BLI standard of care (SOC)	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
Experimental ESCRE/CRE Fluoroquinolone	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention ESCRE/CRE Fluoroquinolone standard of care (SOC)	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone standard of care (SOC)
Experimental MRSA lipo/glycopeptide	MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention MRSA lipo/glycopeptide standard of care (SOC)	MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide standard of care (SOC)
Experimental MRSA oxazolidinone	MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention MRSA oxazolidinone standard of care (SOC)	MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone standard of care (SOC)
Experimental MDR-PA BL-BLI	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention MDR-PA BL-BLI standard of care (SOC)	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
Experimental MDR-PA carbapenem +/- BLI	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention MDR-PA carbapenem +/- BLI standard of care (SOC)	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
Experimental MDR-PA Fluoroquinolone	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention MDR-PA Fluoroquinolone standard of care (SOC)	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone standard of care (SOC)
Experimental VRE lipopeptide	MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention VRE lipopeptide standard of care (SOC)	MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide standard of care (SOC)
Experimental VRE oxazolidinone	MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention VRE oxazolidinone standard of care (SOC)	MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone standard of care (SOC)
Experimental ESCRE/CRE cefepime/cefidericol	MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention ESCRE/CRE cefepime/cefidericol standard of care (SOC)	MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol standard of care (SOC)
Experimental MDR-PA cefepime/cefidericol	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol	Drug: PMT Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002) Other names: Penn Microbiome Therapy
No Intervention MDR-PA cefepime/cefidericol standard of care (SOC)	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol standard of care (SOC)

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington University
St Louis 4407066, Missouri 4398678 63110

Contact:
Michael Klebert, PhD, RN, ANP-BC
(314) 454-0058
mklebert@wustl.edu

More Details

NCT ID: NCT05632315
Status: Recruiting
Sponsor: University of Pennsylvania

Study Contact

Brendan J Kelly, MD, MS
(215) 662-6932
brendank@pennmedicine.upenn.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.