PMT for MDRO Decolonization

A Phase II Randomized Trial to Evaluate the Impact of Fecal Microbiota Transplantation Using the Penn Microbiome Therapy Products on Recipient and Environmental Colonization With Multidrug-Resistant Organisms

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Enterobacteriaceae Infections; Methicillin-resistant Staphylococcus Aureus; Pseudomonas Aeruginosa; VRE Infection; Multidrug Resistant Bacterial Infection
• Intervention / Treatment: Drug: PMT

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Brendan J Kelly, MD, MS; Phone Number: (215) 662-6932; Email: brendank@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 resistant 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 planned completion of antibiotic treatment for 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 (ANC < 1000 cells/uL) or severe (ANC < 500 cells/uL) neutropenia.
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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

24

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 resistant 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 resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
Experimental: MDR-PA carbapenem +/- BLI; MDRO: two-class resistant 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 resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
Experimental: MDR-PA Fluoroquinolone; MDRO: two-class resistant 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 resistant 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 resistant 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 resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol standard of care (SOC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with resolution of index MDRO colonization of the gut	measured by selective stool culture, resolution will be defined as the absence of growth of the index MDRO on selective culture media.	30 (+/-7)- day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Frequency of solicited adverse events (AEs)		randomization until 180 day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Frequency of serious adverse events (SAEs)		randomization until 180 day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Frequency of adverse events of special interest (AESIs)		randomization until 180 day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Frequency of medically attended adverse events (MAAEs)		randomization until 180 day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication of gut colonization with the index MDRO	i.e., negative selective bacterial culture for the index MDRO to be assessed in addition to primary endpoint	7 days and 90 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Eradication of gut colonization with any of the included MDROs		7- , 30-, and 90-days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
All-cause mortality		30- and 60-days following SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Cumulative days of hospitalization		from randomization to 30 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Cumulative days of intensive care		from randomization to 30 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Hospital admission		within 60 days of discharge from index hospitalization
Colectomy occurrence		within 30 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Bacteria growth in blood samples		from randomization to 30 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Hospital admission		within 180 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Instances of worsened abdominal pain, fever, tachycardia, and hypotension		randomization until 180-day visit
Instances of aspiration (including reduced oxygen saturation, tachypnea, or respiratory distress (PMT-002 upper entral delivery only)		randomization until 180-day visit
Instances of fever, diarrhea, nausea and vomiting		7-, 30-, 90- and 180 day follow up visits
Instances of new metabolic disease, including hyperglycemia, thyroid disease, weight gain or loss		30-, 90- and 180 day follow up visits

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Brendan J Kelly, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: November 17, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Bacterial Infections; Enterobacteriaceae Infections
• Other Study ID Numbers: 852552

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No