Bacteriophage Therapy in Patients With Prosthetic Joint Infections

Study Overview
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Brief Summary
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This is a study designed to evaluate bacteriophage therapy in patients with chronic prosthetic joint infections.

Detailed Description
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This is a study designed to evaluate bacteriophage therapy in patients with chronic prosthetic joint infections of the hip or knee caused by 1 or 2 of the following organisms: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus sp., Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and/or Klebsiella pneumoniae. This study will also compare the safety and efficacy of phage therapy in conjunction with antibiotics versus standard of care (SOC) two-stage exchange arthroplasty plus antibiotics.

Official Title
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Randomized Open Label, Parallel Group, Controlled Study to Evaluate the Safety and Surgery Sparing Effect of Phage Therapy With Antibiotics for Patients With Prosthetic Joint Infections Who Are Candidates for Two Stage Exchange Arthroplasty

Conditions
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Prosthetic Joint Infection

Intervention / Treatment
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* Biological: Phage Therapy
* Procedure: Two-Stage Exchange Arthroplasty


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria: Males or females ≥18 years of age. Female patients of childbearing potential who agree to use contraception. Candidate for a two-stage exchange arthroplasty. Chronic prosthetic joint infection General Exclusion Criteria: Prior history of prosthetic joint infections (PJI) of same joint treated surgically other than one prior Debridement Antibiotics and Implant Retention procedure Soft tissue defect requiring reconstruction Hardware misalignment or loosening Active osteomyelitis Septic shock or hemodynamic instability Stage 4 or greater chronic kidney disease Liver disease Decompensated cirrhosis Alcohol abuse or alcohol induced liver disease or non-alcoholic steatohepatitis Decompensated heart failure Any other clinically significant disease, per judgement of the investigator Neutropenia (neutrophil count < 1000 cells/cubic mm), thrombocytopenia (platelets < 50,000/cubic mm) or aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 3 time the upper limit of normal HIV, hepatitis C, hepatitis B infection Positive drug screen Receipt of chemotherapy, immunosuppressants or immune modulators Anti-viral medication Any known phage allergy Breast feeding or pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, open-label, parallel-group design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1, Phage Therapy with Antibiotic Treatment<br>Phage therapy will be administered in conjunction with antibiotic treatment. | Biological: Phage Therapy<br>* Phage will be administered based on patient's matching results.<br>* Other names: Antibiotics;|
| Active Comparator: Arm 2, Standard of Care<br>Two-stage exchange arthroplasty entails resection arthroplasty and placement of an antibiotic-loaded spacer, antibiotic therapy, an antibiotic-free observation period, and re-implantation of a new prosthesis. | Procedure: Two-Stage Exchange Arthroplasty<br>* Performed per the study center's standard of care. No investigational products are used.<br>* Other names: Antibiotics;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of phage therapy | Incidence and type of adverse events and infusion reactions | Day 1 through Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of phage therapy to prevent need for surgery in patients with hip/knee prosthetic joint infections. | Proportion of phage-treated patients with no need for surgery by no evidence of a prosthetic joint infection. | 6 weeks after completion of phage therapy | 
| Efficacy of phage therapy in hip joint functionality as assessed by hip disability and osteoarthritis outcome questionnaire score (HOOS). | Time to reach minimum clinically important difference in hip dysfunction and osteoarthritis outcome score. | Week 26 | 
| Efficacy of phage therapy in knee joint functionality as assessed by knee injury and osteoarthritis outcome questionnaire score (KOOS). | Time to reach minimum clinically important difference in knee injury and osteoarthritis outcome score. | Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prosthetic, Joint, Knee, Hip, Phage, Bacteriophage, Prosthetic Joint