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
Overview
- Phase
- Phase 2
- Intervention
- PMT
- Conditions
- Multidrug Resistant Bacterial Infection
- Sponsor
- University of Pennsylvania
- Enrollment
- 32
- Locations
- 6
- Primary Endpoint
- Proportion of subjects with resolution of index MDRO colonization of the gut
- Status
- Active, Not Recruiting
- Last Updated
- 19 days ago
Overview
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.
Investigators
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 non-susceptible 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 SCAIM (scheduled completion of inpatient appropriate antibiotics for the 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 or severe neutropenia within 10 calendar days prior to enrollment.
- •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
Arms & Interventions
ESCRE/CRE BL-BLI
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
Intervention: PMT
ESCRE/CRE carbapenem +/- BLI
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI
Intervention: PMT
ESCRE/CRE Fluoroquinolone
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone
Intervention: PMT
MRSA lipo/glycopeptide
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide
Intervention: PMT
MRSA oxazolidinone
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone
Intervention: PMT
MDR-PA BL-BLI
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
Intervention: PMT
MDR-PA carbapenem +/- BLI
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI
Intervention: PMT
ESCRE/CRE carbapenem +/- BLI standard of care (SOC)
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
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)
ESCRE/CRE Fluoroquinolone standard of care (SOC)
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone standard of care (SOC)
MRSA lipo/glycopeptide standard of care (SOC)
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide standard of care (SOC)
MRSA oxazolidinone standard of care (SOC)
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone standard of care (SOC)
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)
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)
MDR-PA Fluoroquinolone standard of care (SOC)
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone standard of care (SOC)
VRE lipopeptide standard of care (SOC)
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide standard of care (SOC)
VRE oxazolidinone standard of care (SOC)
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone standard of care (SOC)
ESCRE/CRE cefepime/cefidericol standard of care (SOC)
MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol standard of care (SOC)
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)
MDR-PA Fluoroquinolone
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone
Intervention: PMT
VRE lipopeptide
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide
Intervention: PMT
VRE oxazolidinone
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone
Intervention: PMT
ESCRE/CRE cefepime/cefidericol
MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol
Intervention: PMT
MDR-PA cefepime/cefidericol
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol
Intervention: PMT
Outcomes
Primary Outcomes
Proportion of subjects with resolution of index MDRO colonization of the gut
Time Frame: 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)
Time Frame: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Frequency of serious adverse events (SAEs)
Time Frame: 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)
Time Frame: 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)
Time Frame: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Secondary Outcomes
- Hospital admission(within 60 days of discharge from index hospitalization)
- 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))
- 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))
- Colectomy occurrence(within 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- Cumulative days of hospitalization(from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- 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)