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

  1. 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

  1. 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

ArmDescriptionAssigned 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