Adult with an staphylococcal prosthetic joint infection treated with debridement, antibiotics and implant retention (DAIR strategy) MedDRA version: 20.0 Level: LLT Classification code 10065011 Term: Prosthesis related infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: RIFABUTINE
MYCOBUTIN
Pharmaceutical Form: Capsule
Trade Name: RIFAMPICINE
Pharmaceutical Form: Capsule
Sponsors
CH Tourcoing
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Hip or knee Prosthetic joint infection treated by debridement, antibiotic therapy initiation and retention of prothesis (DAIR strategy) 2.Microbiologically documented infection corresponds to the isolation of staphylococcus aureus or coagulase-negative Staphylococcus aureus from reliable samples: intraoperatively (= 3 during synovectomy-washing), joint puncture or blood culture; the microorganism(s) will be considered pathogenic if identified in = 2 reliable samples. 3.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. 4.Age = 18 years 5.At least 2 days of appropriate (i.e., covering pathogen(s) identified in the intraoperative samples) empirical agents are needed. 6.Signed Inform consent 7.Patient having the rights to French social insurance 8.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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 218 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 218
Exclusion criteria
Exclusion criteria: 1.Known or suspected malabsorption (imperfect absorption of food material by the small intestine) 2.Polymicrobial infection due to other than staphylococcus species susceptible to rifampicin 3.Known or suspected allergy to rifabutin and/or rifampicin 4.Diagnosis of endocarditis associated to PJI 5.Renal transplant or Chronic kidney disease with an eGFR of less than 30ml/min/1.73m² 6.Other Solid Organ Transplant 7.Liver cirrhosis, Child-Pugh score C 8.Any other concomitant infection which required a prolonged course of intravenous antibiotic therapy 9.Oestroprogestative-based contraception 10.Ongoing treatment that contraindicates the use of rifampicin or rifabutine 11.Porphyria 12.Unable to take oral treatment 13.Receive empirical postoperative antibiotic treatment by rifampicin or rifabutin prior to randomization 14.Pregnancy or lactating women 15.Curator or guardianship or patient placed under judicial protection 16.Participation in other interventional research during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that in DAIR strategy for prosthetic joint infection due to staphylococci (S. aureus and CoNS) susceptible or resistant to methicillin, oral rifabutin is non-inferior to oral rifampicin.;Secondary Objective: To compare between allocation arms: 1.Tolerance I: occurrence of serious adverse events (SAEs), including death (i.e. all cause); 2.Tolerance II: occurrence of any adverse event that could be related to rifampicin or rifabutin 3.Tolerance III: Proportion of patients from each arm who will complete the 12-week duration of rifampicin/rifabutin treatment, early termination of the planned 12 weeks’ period of antibiotics; 4.Adherence to antibiotics regimen 5.Quality of life, as evaluated by EQ 5D 3L questionnaire 24; 6.Functional prognosis using Oxford Hip and Knee Scores (Oxford questionnaire) evolution according to location of PJI 25; 7.Long term efficacy of rifampicin and rifabutin treatment (i.e., two year after the surgical intervention) ;Primary end point(s): The primary outcome is treatment failure after one year of follow-up, defined as one of following events: -The need for any further surgical procedure – i.e. implants removal, implants exchange or amputation; - And/or PJI related death; - And/or use of suppressive antibiotic therapy that was not planned before randomization ;Timepoint(s) of evaluation of this end point: After one year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Proportion of patient which are free from SAEs occurrence, as defined by: Patients who completed the entire 12 weeks duration of antibiotic treatment planned initially and; Who did not experience grade 3-4 adverse events, including death, regardless of the link with antibiotic therapy; Who did not experience adverse events which led to either to: •Reduce the dosage or split the treatment to two take/day; •Or stop any component of the antibiotic treatment. 2.Number and rate of patients in each arm who experiences: Liver cytolysis (>=2N for ALT AND/OR AST) Acute Kidney failure as defined by serum creatinine increase in KDIGO 26 Digestive symptoms, including diarrhea Who required a modification of antibiotic dosage during the 12 weeks’ period of antibiotic treatment Uveitis/ophthalmologic disorder Neurological disorder 3.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. 4.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. 5.Quality of life, as evaluated by the use EQ 5D 3L auto-questionnaire at month 1, month 6, month 12 and month 24 as used in previous randomized clinical trial on bone and joint infection 10. 6.Oxford Hip and Knee Scores evolution between month 1, month 6, month 12 and month 24 as used in previous randomized clinical trial on bone and joint infection 10. 7.Long term efficacy: treatment failure, as defined for primary outcome, occurring between 12 months and 24 months after initial surgery. ;Timepoint(s) of evaluation of this end point: 1.12 weeks 2.12 weeks 3.12 weeks 4.12 weeks 5.month 1, month 6, month 12 and month 24 6.month 1, month 6, month 12 and month 24 7. bet | — |
Countries
France
Contacts
Public ContactSolange TREHOUX
CH Tourcoing
Outcome results
None listed