Phage Therapy for MDRO Decolonization

Recruiting at 2 trial locations

Overseen By Brendan J Kelly, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must be taking: Antibiotics

Disqualifiers: Neutropenia, Pregnancy, Gastrointestinal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if fecal microbiota transplant, using Penn Microbiome Therapy products, can eliminate tough, antibiotic-resistant bacteria in the body. Researchers compare this new approach with standard antibiotic treatments for serious infections caused by hard-to-treat bacteria, such as MRSA and VRE. The trial includes different groups testing various treatments to identify the most effective one. Suitable participants have infections in their blood, lungs, or urinary tract that do not respond well to typical antibiotics and are already on an antibiotic treatment plan. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fecal microbiota transplantation (FMT) is generally safe for patients. In a previous study, FMT removed hard-to-treat bacteria from the body, and most patients did not experience serious side effects. Common mild side effects included stomach discomfort, diarrhea, and bloating.

This treatment is currently being tested in a Phase 2 trial, which evaluates its effectiveness and safety. While more information is needed, current evidence suggests that FMT is relatively safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about phage therapy for multi-drug resistant organism (MDRO) decolonization because it offers a unique approach compared to traditional antibiotics. Unlike antibiotics that broadly target bacteria, phage therapy uses viruses (bacteriophages) that specifically target and destroy harmful bacteria without affecting beneficial ones. This precision reduces the risk of disrupting the body's natural microbiome and may help combat antibiotic resistance, a growing global health concern. Additionally, phages can evolve alongside bacteria, potentially maintaining their effectiveness even as bacterial strains mutate. This adaptability makes phage therapy a promising alternative in the fight against stubborn bacterial infections.

What evidence suggests that this trial's treatments could be effective for MDRO decolonization?

Research has shown that fecal microbiota transplantation (FMT) can reduce drug-resistant bacteria in the gut. Past studies have yielded mixed but hopeful results in combating these bacteria. This trial tests the Penn Microbiome Therapy (PMT) as an experimental approach to improve outcomes by using specific gut bacteria to overpower resistant ones. Early signs suggest that PMT might enhance the effectiveness of standard antibiotic treatments. By restoring a healthy bacterial balance, PMT could become an important tool in eliminating antibiotic-resistant infections. ^{1 2 6 7 8}

Who Is on the Research Team?

Brendan J Kelly

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 expected to be treated with antibiotics in the hospital for my infection for at least 5 days.

I am on antibiotics that match my infection's resistance profile.

I have an infection caused by bacteria resistant to multiple antibiotics.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• PMT

Trial Overview

The 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.

How Is the Trial Designed?

Group I: VRE oxazolidinone Experimental Treatment 1 Intervention

MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone

Group II: VRE lipopeptide Experimental Treatment 1 Intervention

MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide

Group III: MRSA oxazolidinone Experimental Treatment 1 Intervention

MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone

Group IV: MRSA lipo/glycopeptide Experimental Treatment 1 Intervention

MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide

Group V: MDR-PA cefepime/cefidericol Experimental Treatment 1 Intervention

MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol

Group VI: MDR-PA carbapenem +/- BLI Experimental Treatment 1 Intervention

MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI

Group VII: MDR-PA Fluoroquinolone Experimental Treatment 1 Intervention

MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone

Group VIII: MDR-PA BL-BLI Experimental Treatment 1 Intervention

MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)

Group IX: ESCRE/CRE cefepime/cefidericol Experimental Treatment 1 Intervention

MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol

Group X: ESCRE/CRE carbapenem +/- BLI Experimental Treatment 1 Intervention

MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI

Group XI: ESCRE/CRE Fluoroquinolone Experimental Treatment 1 Intervention

MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone

Group XII: ESCRE/CRE BL-BLI Experimental Treatment 1 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 Control 1 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 Control 1 Intervention

MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide standard of care (SOC)

Group XV: MRSA oxazolidinone standard of care (SOC) Active Control 1 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 Control 1 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 Control 1 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 Control 1 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 Control 1 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 Control 1 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 Control 1 Intervention

MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone standard of care (SOC)

Group XXII: VRE lipopeptide standard of care (SOC) Active Control 1 Intervention

MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide standard of care (SOC)

Group XXIII: MDR-PA Fluoroquinolone standard of care (SOC) Active Control 1 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 Control 1 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

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridium difficile infection (CDI), and it is now recommended for this specific use.

While FMT shows promise for other gastrointestinal conditions like ulcerative colitis (UC), Crohn's disease (CD), and irritable bowel syndrome (IBS), it is not yet recommended outside of CDI due to safety and efficacy concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for the treatment of patients with ulcerative colitis and other gastrointestinal conditions beyond Clostridium difficile infection: an update. Holleran, G., Scaldaferri, F., Ianiro, G., et al.[2018]

In a study of 20 patients with multidrug-resistant organisms (MDROs), fecal microbiota transplantation (FMT) led to significant reductions in the duration of antibiotic use, instances of bacteremia, and hospital length of stay, despite only modest rates of decolonization of MDROs.

These findings suggest that FMT can be an effective intervention for improving clinical outcomes in patients with MDRO colonization or infection, even if it does not completely eliminate the resistant organisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease Prevention Not Decolonization: A Model for Fecal Microbiota Transplantation in Patients Colonized With Multidrug-resistant Organisms. Ghani, R., Mullish, BH., McDonald, JAK., et al.[2022]

Fecal microbiota transplantation (FMT) was performed on 26 patients with recurrent Clostridium difficile infection, showing a 92% success rate in preventing further diarrhea or CDI relapse over a follow-up period of up to 30 months.

The procedure was found to be simple and safe, with most patients remaining free of significant diarrhea after the treatment, highlighting FMT as a promising alternative to prolonged antibiotic courses for managing recurrent CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. Kelly, CR., de Leon, L., Jasutkar, N.[2022]

In a study of 186 patients with IBS, fecal microbiota transplantation (FMT) administered to the small intestine (duodenum) showed a significantly higher long-term response rate compared to administration to the large intestine (colon) after 12 months.

Repeating the FMT procedure in the small intestine resulted in greater improvements in symptoms and quality of life than a single FMT, indicating that multiple treatments may enhance the benefits of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting the outcome of fecal microbiota transplantation for patients with irritable bowel syndrome. El-Salhy, M., Gilja, OH., Hatlebakk, JG.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplanting a Microbial Organ: the Good, the Bad, and the Unknown. Antonopoulos, DA., Chang, EB.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Roles of the Virome in Cancer. Broecker, F., Moelling, K.[2021]

Fecal microbiota transplantation (FMT) successfully cured a patient with recurrent C. difficile infection, and the patient has remained symptom-free for over 5 years, indicating the long-term efficacy of this treatment.

The analysis revealed that FMT led to a stable and diverse gut microbiota, with beneficial bacteria increasing and harmful bacteria decreasing, suggesting that FMT not only treats rCDI but may also promote overall gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation to fight Clostridium difficile infections and other intestinal diseases. Moelling, K., Broecker, F.[2020]

Fecal microbial transplant (FMT) has shown high efficacy in treating recurrent Clostridium difficile infections, indicating its potential as a powerful therapeutic option for gastrointestinal microbiome issues.

Research is expanding to explore FMT for a variety of other diseases linked to microbiome disturbances, highlighting the growing interest in this treatment approach beyond just gastrointestinal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbial therapy: promises and pitfalls. Merenstein, D., El-Nachef, N., Lynch, SV.[2021]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridioides difficile infection (CDI), achieving resolution rates close to 100%, making it a crucial therapy for this serious condition.

FMT is being explored as a promising treatment for other gastrointestinal disorders, such as inflammatory bowel disease, irritable bowel syndrome, and colon cancer, due to its ability to manipulate the gut microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. Borody, TJ., Eslick, GD., Clancy, RL.[2020]

Fecal microbiome transplant (FMT) is an effective treatment for various gastrointestinal diseases and can help restore a healthy balance in the gut microbiome by using fecal material from healthy donors.

Dysbiosis, or an imbalance in gut bacteria, can lead to serious health issues like infections, cancer, and cardiometabolic diseases, highlighting the importance of FMT in addressing these underlying problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Fecal Microbiome Transplant in Treating Human Diseases: Too Early for Poop? Ser, HL., Letchumanan, V., Goh, BH., et al.[2023]

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