RIFABUTIN for Prosthetic joint infection | Prosthesis related infection

Inclusion criteria

• {"criterion_text":"- Hip or knee Prosthetic joint infection treated by debridement, antibiotic therapy initiation and retention of prothesis (DAIR strategy)\n- Microbiologically documented infection corresponds to the isolation of staphylococcus aureus or coagulase-negative Staphylococcus aureus from reliable samples: intraoperatively (≥ 3 during synovectomywashing), joint puncture or blood culture; the microorganism(s) will be considered pathogenic if identified in ≥ 2 reliable samples.\n- Microorganisms susceptible to rifampicin and at least one other antibiotic suitable for the treatment of PJI (e.g., penicillin, fluoroquinolone, (doxy/mino)cycline, oxazolidinone, cotrimoxazole, daptomycin, glycopeptide, macrolide, fusidic acid), regardless of sensitivity to methicillin.\n- Age ≥ 18 years\n- At least 2 days of appropriate (i.e., covering pathogen(s) identified in the intraoperative samples) empirical agents are needed.\n- Signed Inform consent\n- Patient having the rights to French social insurance\n- For women of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile and excluding oestroprogestative-based contraception, any effective contraceptive: vasectomy (for men), intrauterine device copper, feminine sterilization, condom, sexual abstinence is required. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause."}

Exclusion criteria

• {"criterion_text":"- Known or suspected malabsorption (imperfect absorption of food material by the small intestine)\n- Ongoing treatment that contraindicates the use of rifampicin or rifabutine\n- Porphyria\n- Unable to take oral treatment\n- Receive empirical postoperative antibiotic treatment by rifampicin or rifabutin prior to randomization\n- Pregnancy or lactating women\n- Curator or guardianship or patient placed under judicial protection\n- Participation in other interventional research during the study\n- Polymicrobial infection due to other than staphylococcus species susceptible to rifampicin\n- Known or suspected allergy to rifabutin and/or rifampicin\n- Diagnosis of endocarditis associated to PJI\n- Renal transplant or Chronic kidney disease with an eGFR of less than 30ml/min/1.73m²\n- Other Solid Organ Transplant\n- Liver cirrhosis, Child-Pugh score C\n- Any other concomitant infection which required a prolonged course of intravenous antibiotic therapy\n- Oestroprogestative-based contraception"}

Primary endpoints

• {"endpoint_text":"- The primary outcome is treatment failure after one year of follow-up, defined as one of following events: \tThe need for any further surgical procedure – i.e. implants removal, implants exchange or amputation; \tAnd/or PJI related death; \tAnd/or use of suppressive antibiotic therapy that was not planned before randomization","definition_or_measurement_approach":"Treatment failure measured at one year of follow-up and defined as occurrence of any of: need for any further surgical procedure (implant removal/exchange or amputation); PJI-related death; or use of unplanned long-term suppressive antibiotic therapy."}

Secondary endpoints

• {"endpoint_text":"- Proportion of patient which are free from SAEs occurrence, as defined by: o\tPatients who completed the entire 12 weeks’ duration of antibiotic treatment planned initially and; \tWho did not experience grade 3-4 adverse events, including death, regardless of the link with antibiotic therapy; \tWho did not experience adverse events which led to either to: •\tReduce the dosage or split the treatment to two take/day; •\tOr stop any component of the antibiotic treatment.","definition_or_measurement_approach":"Measured as proportion of patients in each arm who completed planned 12-week antibiotic treatment without grade 3-4 AEs (including death) and without AEs leading to dose reduction, dose splitting, or stopping any antibiotic component."}
• {"endpoint_text":"- Number and rate of patients in each arm who experiences: o\tLiver cytolysis (>=2N for ALT AND/OR AST) o\tAcute Kidney failure as defined by serum creatinine increase in KDIGO o\tDigestive symptoms, including diarrhea o\tWho required a modification of antibiotic dosage during the 12 weeks’ period of antibiotic treatment o\tUveitis/ophthalmologic disorder o\tNeurological disorder","definition_or_measurement_approach":"Count and incidence rate per arm of listed specific adverse events and treatment modifications during 12 weeks of antibiotic therapy; liver cytolysis defined as ≥2x normal for ALT and/or AST; acute kidney failure per KDIGO criteria."}
• {"endpoint_text":"- Early termination rate will be measured in each arm, as the number of patients having stopped rifampicin or rifabutin before the planned 12 weeks’ period over the total number of patients enrolled in the studied arm.","definition_or_measurement_approach":"Proportion of patients per arm who discontinue rifampicin/rifabutin before completing planned 12 weeks."}
• {"endpoint_text":"- Adherence rate to medication will be measured as the number of days on which all doses were missed over the number of days of planned antibiotic therapy. Patients enrolled in the study will have to fill their pill count in a daily notebook.","definition_or_measurement_approach":"Adherence measured via patient daily notebook pill counts; calculated as number of days with all doses missed divided by planned therapy days."}
• {"endpoint_text":"- Quality of life, as evaluated by the use EQ5D5L auto-questionnaire at week 6, month 6, month 12 and month 24 as used in previous randomized clinical trial on bone and joint infection.","definition_or_measurement_approach":"EQ-5D-5L self-administered questionnaire at specified timepoints (week 6, month 6, month 12, month 24)."}
• {"endpoint_text":"- Oxford Hip and Knee Scores evolution between week 6, month 6, month 12 and month 24 as used in previous randomized clinical trial on bone and joint infection.","definition_or_measurement_approach":"Oxford Hip and Knee Score assessments at week 6, month 6, month 12 and month 24 to evaluate functional outcome changes."}
• {"endpoint_text":"- Long term efficacy: treatment failure, as defined for primary outcome, occurring between 12 months and 24 months after initial surgery.","definition_or_measurement_approach":"Occurrence of treatment failure (as primary outcome definition) between 12 and 24 months post-surgery."}

France

Earliest CTIS Part Ii Submission Date

31-01-2025

Latest Decision Or Authorization Date

07-02-2025

Processing Time Days

7

Number Of Sites

36

Number Of Participants

436

Primary sponsor

Full Name

Centre Hospitalier De Tourcoing

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France