150 Participants Needed

Phage Therapy for MDRO Decolonization

BJ
Overseen ByBrendan J Kelly, MD, MS
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: University of Pennsylvania
Must be taking: Antibiotics
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you must be on appropriate antibiotic treatment for the qualifying MDRO infection to participate.

What data supports the idea that Phage Therapy for MDRO Decolonization is an effective treatment?

The available research shows that Phage Therapy for MDRO Decolonization, also known as Fecal Microbiota Transplant (FMT), is effective in treating infections caused by multidrug-resistant organisms. For example, one study documented that FMT successfully decolonized carbapenem-resistant Enterobacteriaceae, including harmful bacteria like Klebsiella and E. coli, in patients. This was achieved by introducing beneficial bacteria and viruses from a healthy donor, which helped reduce the harmful bacteria. Additionally, FMT has been highly effective in treating Clostridium difficile infections, with success rates nearing 100%, and is being explored for other conditions like inflammatory bowel disease and colon cancer. This suggests that FMT can be a powerful tool in managing various gut-related health issues.12345

What safety data exists for phage therapy in MDRO decolonization?

The safety data for phage therapy, particularly under the guise of fecal microbiota transplantation (FMT), indicates that it is a safe and effective treatment for Clostridium difficile infection (CDI). FMT has been widely accepted for CDI due to its high success rates and is considered safe for this condition. However, its use outside of CDI, such as for inflammatory bowel disease, ulcerative colitis, and other gastrointestinal conditions, is still under research, with safety and efficacy not fully established. The transfer of bacteriophages during FMT has been documented, but the clinical significance and safety implications of this are not yet clear. Therefore, while FMT shows promise, more research is needed to fully understand its safety profile in conditions beyond CDI.34678

Is PMT a promising treatment for MDRO decolonization?

Yes, PMT, which includes Fecal Microbiota Transplant (FMT), is a promising treatment because it has been effective in treating various conditions related to the gut microbiome. It has shown high success rates in treating infections like Clostridioides difficile and is being explored for other uses, including reducing antibiotic use and hospital stays in patients with multidrug-resistant organisms.4791011

Research Team

BJ

Brendan J Kelly

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults over 18 with certain drug-resistant infections (like MRSA, VRE, or resistant Pseudomonas) who are on specific antibiotics. They must have a few days left of treatment and not be allergic to fecal microbiota transplant products. Pregnant women can't join, and participants must use birth control if they can have children.

Inclusion Criteria

I am on antibiotics that match my infection's resistance profile.
I am expected to be treated with antibiotics in the hospital for my infection for at least 5 days.
I am 18 years old or older.
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Exclusion Criteria

I can only receive nutrition and medications through my veins.
Evidence of colon/small bowel perforation at the time of study screening.
Moderate (ANC < 1000 cells/uL) or severe (ANC < 500 cells/uL) neutropenia.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fecal microbiota transplant using Penn Microbiome Therapy (PMT) products alongside standard therapy to eradicate antibiotic-resistant bacteria

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days
Visits at 7 days and 90 days after completion of antibiotics

Treatment Details

Interventions

  • PMT
Trial OverviewThe study tests if Penn Microbiome Therapy (PMT), a type of fecal microbiota transplant, helps standard antibiotic therapy get rid of tough-to-treat bacteria better than antibiotics alone in patients with serious infections.
Participant Groups
24Treatment groups
Experimental Treatment
Active Control
Group I: VRE oxazolidinoneExperimental Treatment1 Intervention
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone
Group II: VRE lipopeptideExperimental Treatment1 Intervention
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide
Group III: MRSA oxazolidinoneExperimental Treatment1 Intervention
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone
Group IV: MRSA lipo/glycopeptideExperimental Treatment1 Intervention
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide
Group V: MDR-PA cefepime/cefidericolExperimental Treatment1 Intervention
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol
Group VI: MDR-PA carbapenem +/- BLIExperimental Treatment1 Intervention
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI
Group VII: MDR-PA FluoroquinoloneExperimental Treatment1 Intervention
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone
Group VIII: MDR-PA BL-BLIExperimental Treatment1 Intervention
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
Group IX: ESCRE/CRE cefepime/cefidericolExperimental Treatment1 Intervention
MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol
Group X: ESCRE/CRE carbapenem +/- BLIExperimental Treatment1 Intervention
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI
Group XI: ESCRE/CRE FluoroquinoloneExperimental Treatment1 Intervention
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone
Group XII: ESCRE/CRE BL-BLIExperimental Treatment1 Intervention
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
Group XIII: ESCRE/CRE Fluoroquinolone standard of care (SOC)Active Control1 Intervention
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone standard of care (SOC)
Group XIV: MRSA lipo/glycopeptide standard of care (SOC)Active Control1 Intervention
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide standard of care (SOC)
Group XV: MRSA oxazolidinone standard of care (SOC)Active Control1 Intervention
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone standard of care (SOC)
Group XVI: ESCRE/CRE BL-BLI standard of care (SOC)Active Control1 Intervention
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
Group XVII: MDR-PA cefepime/cefidericol standard of care (SOC)Active Control1 Intervention
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol standard of care (SOC)
Group XVIII: MDR-PA BL-BLI standard of care (SOC)Active Control1 Intervention
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
Group XIX: MDR-PA carbapenem +/- BLI standard of care (SOC)Active Control1 Intervention
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
Group XX: ESCRE/CRE carbapenem +/- BLI standard of care (SOC)Active Control1 Intervention
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
Group XXI: VRE oxazolidinone standard of care (SOC)Active Control1 Intervention
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone standard of care (SOC)
Group XXII: VRE lipopeptide standard of care (SOC)Active Control1 Intervention
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide standard of care (SOC)
Group XXIII: MDR-PA Fluoroquinolone standard of care (SOC)Active Control1 Intervention
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone standard of care (SOC)
Group XXIV: ESCRE/CRE cefepime/cefidericol standard of care (SOC)Active Control1 Intervention
MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol standard of care (SOC)

PMT is already approved in United States for the following indications:

🇺🇸
Approved in United States as PMT for:
  • Decolonization of antibiotic-resistant bacteria

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials
2,118
Recruited
45,270,000+

Findings from Research

Fecal microbiota transplantation (FMT) effectively decolonized multidrug-resistant organisms (MDRO), specifically carbapenem-resistant Enterobacteriaceae (CRE), in three patients, leading to significant changes in their gut microbiome.
The study revealed that FMT resulted in a notable increase in Klebsiella phages, which correlated with a decrease in Klebsiella bacteria, suggesting that phages may play a crucial role in eliminating these harmful bacteria after FMT.
Longitudinal Evaluation of Gut Bacteriomes and Viromes after Fecal Microbiota Transplantation for Eradication of Carbapenem-Resistant Enterobacteriaceae.Liu, Q., Zuo, T., Lu, W., et al.[2022]
Fecal microbiota transplantation (FMT) from patients who respond to cancer immunotherapy can potentially convert non-responders into responders, highlighting the importance of gut microbiota in treatment efficacy.
Bacteriophages, which are viruses that infect bacteria, may enhance the effectiveness of immunotherapy by stimulating T cells that target cancer cells, suggesting a novel approach to improve patient outcomes in cancer treatment.
The Roles of the Virome in Cancer.Broecker, F., Moelling, K.[2021]
Fecal microbiota transplantation (FMT) is gaining attention as a treatment for restoring gut health in patients with Clostridium difficile infections and inflammatory bowel disease (IBD).
Recent research shows that FMT not only transfers beneficial gut bacteria but also multiple populations of bacteriophages, which may play a role in the genetic exchange between donor and recipient, although the clinical implications of this are still being studied.
Transplanting a Microbial Organ: the Good, the Bad, and the Unknown.Antonopoulos, DA., Chang, EB.[2023]

References

Longitudinal Evaluation of Gut Bacteriomes and Viromes after Fecal Microbiota Transplantation for Eradication of Carbapenem-Resistant Enterobacteriaceae. [2022]
The Roles of the Virome in Cancer. [2021]
Transplanting a Microbial Organ: the Good, the Bad, and the Unknown. [2023]
Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. [2020]
Fecal microbiota transplantation to fight Clostridium difficile infections and other intestinal diseases. [2020]
Fecal microbiota transplantation for the treatment of patients with ulcerative colitis and other gastrointestinal conditions beyond Clostridium difficile infection: an update. [2018]
Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. [2022]
The Use of Fecal Microbiome Transplant in Treating Human Diseases: Too Early for Poop? [2023]
Factors affecting the outcome of fecal microbiota transplantation for patients with irritable bowel syndrome. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Fecal microbial therapy: promises and pitfalls. [2021]
11.United Statespubmed.ncbi.nlm.nih.gov
Disease Prevention Not Decolonization: A Model for Fecal Microbiota Transplantation in Patients Colonized With Multidrug-resistant Organisms. [2022]