Enterobacteriaceae Infections, Methicillin-resistant Staphylococcus Aureus, Multidrug Resistant Bacterial Infection, Pseudomonas Aeruginosa, VRE Infection
Conditions
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.
Interventions
DRUGPMT
Fecal Microbiota for Transplant, enema product (PMT-001) or Fecal Microbiota for Transplant, suspension product (PMT-002)
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, open label, comparative
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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 60 days of discharge from index hospitalization | — |
| 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 | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBrendan J Kelly
University of Pennsylvania
Outcome results
None listed