knee or hip prosthetic infection Prosthetic joint infection
Conditions
Interventions
anti- Staphylococcus aureus bacteriophages
Sponsors
Phaxiam Therapeutics
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female >= 18 years 2. Staphylococcus aureus monomicrobial knee or hip PJI *1 month after prosthesis implantation with clinical signs of infection and with indication of DAIR with direct closure (if associated flap, arthrotomy must be sealed), and Suppressive Antibiotics Therapy (SAT) 3. 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 4. Without preoperative diagnosis of superinfection due to another pathogen if treatment is administered at the end of the DAIR 5. Without diagnosis of superinfection due to another pathogen identified within 72h after a bacteriological sample performed during a DAIR if treatment is administered 14±2 days after a DAIR. 6. Phagogram displaying the susceptibility of the strain to at least one of the phages. 7. Patient with a life expectancy of 2 years and more as determined by the principal investigator 8. Females of childbearing potential/Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable effective method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices, condom) for 1 month after the last study drug administration 9. Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months) 10. Negative pregnancy test 11. Signing a written informed consent before any study related procedures including phagogram 12. Affiliated to a national social security system and / or private health insurance in compliance with the
Exclusion criteria
Exclusion criteria: 1. Early Staphylococcus aureus Prosthesis Joint infection (*1month after the prosthesis implantation) 2. Other germ found in culture of joint fluid sample 3. Phagogram displaying no susceptibility of the strain to anti-Staphylococcus aureus bacteriophages 4. Patients with ASA score >= 4 5. Severe sepsis or Septic shock or hemodynamic instability 6. Patients with an indication to prosthesis replacement or amputation 7. Immunosuppressed patients 8. Known allergic reactions to components of phages products 9. Relapse between DAIR and treatment administration planned 14±2 days after a DAIR 10. Medical history which in the opinion of the investigator would mean that the patient is unsuitable for participation in the study 11. Patient who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development 12. Currently in exclusion period from a previous study 13. Concomitant participation to another interventional clinical trial or previous participation with active drug levels still present, i.e. the last medication intake is less than 4 half-lives ago 14. Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period and up to 1 month after the last administration of study drug 15. Women/Men refusing to use an acceptable effective contraception during 1 month after the last administration of study drug 16. No possibility of contact in case of emergency 17. Minors, persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care and persons admitted to a health or social institution, to adult patient under legal protection or unable to express consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical control of infection at week 12±2 defined by: - no clinical signs of evolutive infection: o no fever (defined by a temperature less than 38°C) due to prosthesis infection o no recurrence, no worsening pain assessed with an Visual Analog Scale (VAS) and defined by an VAS at Week 12 below VAS prior to D0 - Peri articular Inflammatory and infectious Clinical signs will be collected : o No local post surgical recurrence or worsening of local articular swelling o No unusual aspect of scar as erythema or abnormal flow or a fistula or inflammatory or local necrosis or no healing - and no new surgical procedure requested before Week 12±2 and no Staphylococcus aureus detected in joint fluid in case of aspiration for suspicion of relapse before Week 12±2 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety parameters: adverse events, physical examination, biological tests as hematology and biochemistry during the whole study; 2. Initial activity of phages: active bacteriophages (PP1493 and/or PP1815) according to phagogram results in regard of the clinical outcome (infection control or relapse) of patients at Week 12±2 3. Clinical control of the infection (as described in primary endpoint) at Week 12±2 for superinfected patients (other species isolated during the surgical procedure) 4. In case of failure before Week 12±2, aspiration of joint fluid at time of failure for microbiological test and identification of Staphylococcus aureus strain: antibiogram and phagogram 5. Microbiology: - Joint fluid: Staphylococcus aureus quantification (CFU and qPCR) at D0 for THA and TKA at D14±1 only for TKA 6. Immunology: - Serum: anti Staphylococcus aureus phage antibodies, at D0, D2, D4, D14±1, D28±2 and Week 12±2 and IL-6 at D0, D14±1 and W12±2 - Joint fluid: anti Staphylococcus aureus phage antibodies at D0 and at D14±1 only for patients with TKA 7. Pharmacokinetics: - Serum: quantification of the phages by qPCR at D0, D0T4H, D2, D4, D14±1, D28±2 and Week 12±2 - Blood: quantification of the phages by plaque assay at D0, D0T4H, D2, D4, D14±1, D28±2 and Week 12±2 for patients in sites in Paris, Nantes and Lyon - Joint Fluid: quantification of the phage by qPCR and plaque assay at D0 and at D14±1 only for patients with TKA; the plaque assay will be performed only for patients in sites in Paris, Nantes and Lyon; 8. Duration of hospitalization 9. Questionnaire EQ-5D-5L for quality of life at each visit (except D14±1 and D28±2); 10. Evaluation of joint function during the pre-inclusion period or at D-1, Week 12±2, Month 6 ±2 weeks, Month 12±1, Month 18±1 and Month 24±2 with: - Knee: KOOS 12-Knee Survey - Hip: HOOS 12-Hip Survey; 11. Clinical control of the infection (as described in primary endpoint) at Month 6±2 weeks, Month 12±1, Month 18 | — |
Countries
Netherlands
Outcome results
None listed