Clinical trial NCT05632315: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multidrug Resistant Bacterial Infection
Enterobacteriaceae Infections
Pseudomonas Aeruginosa
VRE Infection
Methicillin-resistant Staphylococcus Aureus
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2022-11-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, open label, comparative
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of subjects with resolution of index MDRO colonization of the gut
timeFrame: 30 (+/-7)- day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Frequency of solicited adverse events (AEs)
timeFrame: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Frequency of serious adverse events (SAEs)
timeFrame: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Frequency of adverse events of special interest (AESIs)
timeFrame: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Frequency of medically attended adverse events (MAAEs)
timeFrame: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Secondary outcomes:
measure: Eradication of gut colonization with the index MDRO
timeFrame: 7 days and 90 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Eradication of gut colonization with any of the included MDROs
timeFrame: 7- , 30-, and 90-days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: All-cause mortality
timeFrame: 30- and 60-days following SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Colectomy occurrence
timeFrame: within 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Cumulative days of hospitalization
timeFrame: from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Cumulative days of intensive care
timeFrame: from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Bacteria growth in blood samples
timeFrame: from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Hospital admission
timeFrame: within 60 days of discharge from index hospitalization
measure: Hospital admission
timeFrame: within 180 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measure: Instances of worsened abdominal pain, fever, tachycardia, and hypotension
timeFrame: randomization until 180-day visit
measure: Instances of aspiration (including reduced oxygen saturation, tachypnea, or respiratory distress (PMT-002 upper entral delivery only)
timeFrame: randomization until 180-day visit
measure: Instances of fever, diarrhea, nausea and vomiting
timeFrame: 7-, 30-, 90- and 180 day follow up visits
measure: Instances of new metabolic disease, including hyperglycemia, thyroid disease, weight gain or loss
timeFrame: 30-, 90- and 180 day follow up visits
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Brendan J Kelly
role: PRINCIPAL_INVESTIGATOR
References: