Phage Therapy in Prosthetic Joint Infection Due to Staphylococcus Aureus Treated With DAIR.

Study Overview
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Brief Summary
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Pilot non comparative study assessing the clinical control of infection of DAIR + SAT +NaCl and DAIR + SAT + Phages anti-Staphylococcus aureus in patients with Staphylococcus aureus Prosthetic Joint Infection with an indication of DAIR + SAT.

Official Title
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A Pilot, Multicenter, Randomized, Non-Comparative, Double-Blind Study of Phage Therapy in Patients With Hip or Knee Prosthetic Joint Infection Due to Staphylococcus Aureus Treated With DAIR and Antibiotic Therapy.

Conditions
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Infection of Total Hip Joint Prosthesis, Infection of Total Knee Joint Prosthesis

Intervention / Treatment
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* Biological: Anti-Staphylococcus aureus Bacteriophages


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years Staphylococcus aureus monomicrobial knee or hip PJI ˃3 months after prosthesis implantation with clinical signs of infection and with indication of DAIR with direct closure and Suppressive Antibiotics Therapy (SAT) Staphylococcus aureus only in joint fluid within 6 months before randomization or in case of relapse of infection under antibiotics therapy after a DAIR performed within 6 months before pre-inclusion visit Without preoperative diagnosis of superinfection due to another pathogen Phagogram displaying the susceptibility of the strain to at least one of the phages. Patient with a life expectancy of 2 years and more as determined by the principal investigator Females of childbearing potential/Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices) for 1 month after the last study drug administration Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months) Negative pregnancy test Exclusion Criteria: Early Staphylococcus aureus Prosthesis Joint infection (˂3months after the prosthesis implantation) Other germ found in culture of joint fluid sample Phagogram displaying no susceptibility of the strain to anti-Staphylococcus aureus bacteriophages Patients with ASA score ≥ 4 Severe sepsis or Septic shock or hemodynamic instability Patients with an indication to prosthesis replacement or amputation Immunosuppressed patients ALT or AST > 5 x ULN, creatinine > 1.53 mg/dl in men and > 1.24 mg/dl in women Known allergic reactions to components of phages products Medical history which in the opinion of the investigator would mean that the patient is unsuitable for participation in the study Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period and 1 month after the last administration of study drug Women/Men refusing to use an effective contraception during 1 month after the last administration of study drug.

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: This is a pilot, randomized, non-comparative, double-blind study in patients with knee or hip prosthetic joint infection (PJI) due to Staphylococcus aureus, with the indication of DAIR and Suppressive Antibiotics Therapy (SAT). A stratification will be performed on the affected area of arthroplasty: knee or hip and on study site.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bacteriophages arm<br>1 mL (PP1493 or PP1815) or 2 mL (PP1493 and PP1815) of suspension of bacteriophages diluted in solution of NaCl 0,9% at the end of DAIR procedure. | Biological: Anti-Staphylococcus aureus Bacteriophages<br>* Single intra-articular injection<br>|
| Placebo Comparator: Control Arm<br>One local administration of NaCl 0,9% solution is administered at the end of the DAIR procedure. | Biological: Anti-Staphylococcus aureus Bacteriophages<br>* Single intra-articular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical control of infection at week 12 visit | No Fever, no recurrence, no worsening of pain, no periarticular inflammatory and clinical infectious signs, no new surgical request, no Staphylococcus aureus detected in joint fluid. | week 12 visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events and Serious Adverse Events | Incidence, severity and type of adverse events and serious adverse events | From the time of signing the informed consent form up to study end visit (Months 24) | 
| Clinical laboratory tests | Number of participants with abnormal clinical laboratory tests | From the time of signing the informed consent form up to study end visit (Months 24) | 
| Physical examination | Number of participants with clinically abnormal physical examination findings | From the time of signing the informed consent form up to study end visit (Months 24) | 
| Clinical control of infection after Week 12 visit | No Fever, no recurrence, no worsening of pain, no periarticular inflammatory and clinical infectious signs, no new surgical request, no Staphylococcus aureus detected in joint fluid | Month 6, Month 12, Month 18 and Month 24. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Joint Infection, Staphylococcus aureus, Phagotherapy