PMT for MDRO Decolonization

Phase 2

Recruiting

• Conditions: Multidrug Resistant Bacterial Infection; Pseudomonas Aeruginosa; Methicillin-resistant Staphylococcus Aureus; Enterobacteriaceae Infections; VRE Infection
• Interventions: Drug: PMT

• Registration Number: NCT05632315
• Lead Sponsor: University of Pennsylvania

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-17
• Study First Submitted QC: 2022-11-17
• Study First Posted: 2022-11-30
• Study Start: 2024-08-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-27
• Primary Completion: 2026-01
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ESCRE/CRE carbapenem +/- BLI	PMT	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI
ESCRE/CRE BL-BLI	PMT	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
ESCRE/CRE Fluoroquinolone	PMT	MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone
MRSA lipo/glycopeptide	PMT	MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide
MRSA oxazolidinone	PMT	MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone
MDR-PA BL-BLI	PMT	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
MDR-PA carbapenem +/- BLI	PMT	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI
MDR-PA Fluoroquinolone	PMT	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone
VRE lipopeptide	PMT	MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide
VRE oxazolidinone	PMT	MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone
ESCRE/CRE cefepime/cefidericol	PMT	MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol
MDR-PA cefepime/cefidericol	PMT	MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Cumulative days of intensive care	from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Bacteria growth in blood samples	from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Hospital admission	within 180 days after SCAIM (scheduled completion of appropriate inpatient 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
Cumulative days of hospitalization	from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Colectomy occurrence	within 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Eradication of gut colonization with the index MDRO	7 days and 90 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)	i.e., negative selective bacterial culture for the index MDRO to be assessed in addition to primary endpoint
Eradication of gut colonization with any of the included MDROs	7- , 30-, and 90-days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
All-cause mortality	30- and 60-days following SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)

Trial Locations

Locations (1)

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States