search
Back to results

PMT for MDRO Decolonization

Primary Purpose

Multidrug Resistant Bacterial Infection, Enterobacteriaceae Infections, Pseudomonas Aeruginosa

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PMT
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multidrug Resistant Bacterial Infection

Eligibility Criteria

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

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 resistant to two or more classes of antibiotics (MDR-PA), vancomycin-resistant Enterococcus (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). 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. Expected duration of inpatient antibiotic treatment for index MDRO infection at least 5 days total. 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. Age ≥ 18 years. Exclusion Criteria: Evidence of colon/small bowel perforation at the time of study screening. Unable to tolerate enteral and enema nutrition and medication administration (i.e., only able to tolerate intravenous nutrition and medications). Goals of care are directed to comfort rather than curative measures. Moderate (ANC < 1000 cells/uL) or severe (ANC < 500 cells/uL) neutropenia. Known food allergy that could lead to anaphylaxis. Known allergy to fecal microbiota transplant products or their components Pregnancy or lactation 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 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 Known gastrointestinal disease that could affect the safety of fecal microbiota transplant at time of enrollment: Inflammatory Bowel Disease (IBD) Short Gut Syndrome Fistulas Bowel resection surgery Colitis

Sites / Locations

  • Hospital of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm 19

Arm 20

Arm 21

Arm 22

Arm 23

Arm 24

Arm Type

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Experimental

No Intervention

Arm Label

ESCRE/CRE BL-BLI

ESCRE/CRE BL-BLI standard of care (SOC)

ESCRE/CRE carbapenem +/- BLI

ESCRE/CRE carbapenem +/- BLI standard of care (SOC)

ESCRE/CRE Fluoroquinolone

ESCRE/CRE Fluoroquinolone standard of care (SOC)

MRSA lipo/glycopeptide

MRSA lipo/glycopeptide standard of care (SOC)

MRSA oxazolidinone

MRSA oxazolidinone standard of care (SOC)

MDR-PA BL-BLI

MDR-PA BL-BLI standard of care (SOC)

MDR-PA carbapenem +/- BLI

MDR-PA carbapenem +/- BLI standard of care (SOC)

MDR-PA Fluoroquinolone

MDR-PA Fluoroquinolone standard of care (SOC)

VRE lipopeptide

VRE lipopeptide standard of care (SOC)

VRE oxazolidinone

VRE oxazolidinone standard of care (SOC)

ESCRE/CRE cefepime/cefidericol

ESCRE/CRE cefepime/cefidericol standard of care (SOC)

MDR-PA cefepime/cefidericol

MDR-PA cefepime/cefidericol standard of care (SOC)

Arm Description

MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)

MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)

MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI

MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI standard of care (SOC)

MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone

MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone standard of care (SOC)

MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide

MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide standard of care (SOC)

MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone

MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone standard of care (SOC)

MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)

MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)

MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI

MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI standard of care (SOC)

MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone

MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone standard of care (SOC)

MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide

MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide standard of care (SOC)

MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone

MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone standard of care (SOC)

MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol

MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol standard of care (SOC)

MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol

MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol standard of care (SOC)

Outcomes

Primary Outcome Measures

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.
Frequency of solicited adverse events (AEs)
Frequency of serious adverse events (SAEs)
Frequency of adverse events of special interest (AESIs)
Frequency of medically attended adverse events (MAAEs)

Secondary Outcome Measures

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
Eradication of gut colonization with any of the included MDROs
All-cause mortality
Colectomy occurrence
Cumulative days of hospitalization
Cumulative days of intensive care
Bacteria growth in blood samples
Hospital admission
Hospital admission
Instances of worsened abdominal pain, fever, tachycardia, and hypotension
Instances of aspiration (including reduced oxygen saturation, tachypnea, or respiratory distress (PMT-002 upper entral delivery only)
Instances of fever, diarrhea, nausea and vomiting
Instances of new metabolic disease, including hyperglycemia, thyroid disease, weight gain or loss

Full Information

First Posted
November 17, 2022
Last Updated
October 17, 2023
Sponsor
University of Pennsylvania
search

1. Study Identification

Unique Protocol Identification Number
NCT05632315
Brief Title
PMT for MDRO Decolonization
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
January 2026 (Anticipated)
Study Completion Date
January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multidrug Resistant Bacterial Infection, Enterobacteriaceae Infections, Pseudomonas Aeruginosa, VRE Infection, Methicillin-resistant Staphylococcus Aureus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, open label, comparative
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ESCRE/CRE BL-BLI
Arm Type
Experimental
Arm Description
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
Arm Title
ESCRE/CRE BL-BLI standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
Arm Title
ESCRE/CRE carbapenem +/- BLI
Arm Type
Experimental
Arm Description
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI
Arm Title
ESCRE/CRE carbapenem +/- BLI standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
Arm Title
ESCRE/CRE Fluoroquinolone
Arm Type
Experimental
Arm Description
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone
Arm Title
ESCRE/CRE Fluoroquinolone standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone standard of care (SOC)
Arm Title
MRSA lipo/glycopeptide
Arm Type
Experimental
Arm Description
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide
Arm Title
MRSA lipo/glycopeptide standard of care (SOC)
Arm Type
No Intervention
Arm Description
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide standard of care (SOC)
Arm Title
MRSA oxazolidinone
Arm Type
Experimental
Arm Description
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone
Arm Title
MRSA oxazolidinone standard of care (SOC)
Arm Type
No Intervention
Arm Description
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone standard of care (SOC)
Arm Title
MDR-PA BL-BLI
Arm Type
Experimental
Arm Description
MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
Arm Title
MDR-PA BL-BLI standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
Arm Title
MDR-PA carbapenem +/- BLI
Arm Type
Experimental
Arm Description
MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI
Arm Title
MDR-PA carbapenem +/- BLI standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
Arm Title
MDR-PA Fluoroquinolone
Arm Type
Experimental
Arm Description
MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone
Arm Title
MDR-PA Fluoroquinolone standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone standard of care (SOC)
Arm Title
VRE lipopeptide
Arm Type
Experimental
Arm Description
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide
Arm Title
VRE lipopeptide standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide standard of care (SOC)
Arm Title
VRE oxazolidinone
Arm Type
Experimental
Arm Description
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone
Arm Title
VRE oxazolidinone standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone standard of care (SOC)
Arm Title
ESCRE/CRE cefepime/cefidericol
Arm Type
Experimental
Arm Description
MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol
Arm Title
ESCRE/CRE cefepime/cefidericol standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol standard of care (SOC)
Arm Title
MDR-PA cefepime/cefidericol
Arm Type
Experimental
Arm Description
MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol
Arm Title
MDR-PA cefepime/cefidericol standard of care (SOC)
Arm Type
No Intervention
Arm Description
MDRO: two-class resistant Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol standard of care (SOC)
Intervention Type
Drug
Intervention Name(s)
PMT
Other Intervention Name(s)
Penn Microbiome Therapy
Intervention Description
Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002)
Primary Outcome Measure Information:
Title
Proportion of subjects with resolution of index MDRO colonization of the gut
Description
measured by selective stool culture, resolution will be defined as the absence of growth of the index MDRO on selective culture media.
Time Frame
30 (+/-7)- day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Frequency of solicited adverse events (AEs)
Time Frame
randomization until 180 day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Frequency of serious adverse events (SAEs)
Time Frame
randomization until 180 day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Frequency of adverse events of special interest (AESIs)
Time Frame
randomization until 180 day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Frequency of medically attended adverse events (MAAEs)
Time Frame
randomization until 180 day visit after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Secondary Outcome Measure Information:
Title
Eradication of gut colonization with the index MDRO
Description
i.e., negative selective bacterial culture for the index MDRO to be assessed in addition to primary endpoint
Time Frame
7 days and 90 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Eradication of gut colonization with any of the included MDROs
Time Frame
7- , 30-, and 90-days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
All-cause mortality
Time Frame
30- and 60-days following SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Colectomy occurrence
Time Frame
within 30 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Cumulative days of hospitalization
Time Frame
from randomization to 30 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Cumulative days of intensive care
Time Frame
from randomization to 30 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Bacteria growth in blood samples
Time Frame
from randomization to 30 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Hospital admission
Time Frame
within 60 days of discharge from index hospitalization
Title
Hospital admission
Time Frame
within 180 days after SCAIM (scheduled completion of appropriate antibiotics for the index MDRO infection)
Title
Instances of worsened abdominal pain, fever, tachycardia, and hypotension
Time Frame
randomization until 180-day visit
Title
Instances of aspiration (including reduced oxygen saturation, tachypnea, or respiratory distress (PMT-002 upper entral delivery only)
Time Frame
randomization until 180-day visit
Title
Instances of fever, diarrhea, nausea and vomiting
Time Frame
7-, 30-, 90- and 180 day follow up visits
Title
Instances of new metabolic disease, including hyperglycemia, thyroid disease, weight gain or loss
Time Frame
30-, 90- and 180 day follow up visits

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 resistant to two or more classes of antibiotics (MDR-PA), vancomycin-resistant Enterococcus (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). 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. Expected duration of inpatient antibiotic treatment for index MDRO infection at least 5 days total. 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. Age ≥ 18 years. Exclusion Criteria: Evidence of colon/small bowel perforation at the time of study screening. Unable to tolerate enteral and enema nutrition and medication administration (i.e., only able to tolerate intravenous nutrition and medications). Goals of care are directed to comfort rather than curative measures. Moderate (ANC < 1000 cells/uL) or severe (ANC < 500 cells/uL) neutropenia. Known food allergy that could lead to anaphylaxis. Known allergy to fecal microbiota transplant products or their components Pregnancy or lactation 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 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 Known gastrointestinal disease that could affect the safety of fecal microbiota transplant at time of enrollment: Inflammatory Bowel Disease (IBD) Short Gut Syndrome Fistulas Bowel resection surgery Colitis
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brendan J Kelly, MD, MS
Phone
(215) 662-6932
Email
brendank@pennmedicine.upenn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brendan J Kelly
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

PMT for MDRO Decolonization

We'll reach out to this number within 24 hrs