PMT for MDRO Decolonization

Study Overview
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Brief Summary
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: PMT


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) | 
| Colectomy occurrence |  | within 30 days after 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) | 
| 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 60 days of discharge from index hospitalization | 
| 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 |