Prosthetic Infection
Conditions
Brief summary
Rifampicin, is key in the treatment of staphylococcal PJIs. Rifabutin has a better profile of tolerance than rifampicin regarding the risk of interaction with concomitant medications and liver disorders. The hypothesis is that rifabutin may be an alternative antibiotic option as efficient as rifampicin for the treatment of staphylococcal PJIs, with a better safety profile. The investigator aim to demonstrate the non-inferiority of rifabutin as compared with rifampicin prescribed in combination treatment for PJIs.
Interventions
DRUGRifabutin
2 tablets of 150 mg per day rifabutin tablet daily for 12 weeks in 1 administration with a companion treatment
DRUGRifampicin
10 mg/kg per day (range 600 mg to 1,200 mg) rifampicin tablet in 1 daily dose for 12 weeks with a companion treatment
Sponsors
Tourcoing Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Hip or knee Prosthetic joint infection treated by debridement, antibiotic therapy initiation and retention of prothesis (DAIR strategy) 2. Infected with at least one of the following microorganisms: 1. Staphylococcus aureus 2. Coagulase-negative staphylococci 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. Pre-randomization antimicrobial therapy could be: flucloxacillin, oxacillin, vancomycin, daptomycin. β-lactam plus β-lactamase-inhibitors (e.g. ampicillin+sulbactam, piperacillin+tazobactam), cephalosporins (except ceftazidime), carbapenems, teicoplanin, ceftaroline, ceftobiprole. 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
Exclusion criteria
1. Suspicion of reduce absorption of oral treatment due to abdominal disorder 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. Oral anticoagulant drugs 11. Other drug-drug interaction that contraindicated rifampicin or rifabutin 12. Porphyria 13. Unable to take oral treatment 14. Receive empirical postoperative antibiotic treatment by rifampicin or rifabutin prior to randomization 15. Pregnancy or lactating women 16. Curator or guardianship or patient placed under judicial protection 17. Participation in other interventional research during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment failure | At one year | Treatment failure 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of serious adverse events (SAEs), including death (i.e. all cause) | At the end of 12 weeks duration of antibiotic treatment planned | 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; xWho did not experience grade 3-4 adverse events, including death, regardless of the link with antibiotic therapy; xWho 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. |
| Occurrence of any adverse event that could be related to rifampicin or rifabutin | At the end of 12 weeks duration of antibiotic treatment planned | 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 * Digestive symptoms, including diarrhea * Who required a modification of antibiotic dosage during the 12 weeks' period of antibiotic treatment * Uveitis/ophthalmologic disorder * Neurological disorder |
| 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 | At the end of 12 weeks duration of antibiotic treatment planned | 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. |
| Adherence to antibiotics regimen | At the end of 12 weeks duration of antibiotic treatment planned | 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. |
| Functional prognosis using Oxford questionnaire evolution according to location of PJI | At the end of the study follow up, an average of 24 months | Oxford Scores as used in previous randomized clinical trial on bone and joint infection |
| Long term efficacy of rifampicin and rifabutin treatment | At the end of the study follow up, an average of 24 months | Long term efficacy: treatment failure, as defined for primary outcome, at 24 months |
| Quality of life, as evaluated by EQ 5D 3L questionnaire | At the end of the study follow up, an average of 24 months | Quality of life, as evaluated by the use EQ 5D 3L auto-questionnaire as used in previous randomized clinical trial on bone and joint infection |
Countries
France
Contacts
Primary ContactEric SENNEVILLE, MD PhD
Backup ContactSolange TREHOUX
Outcome results
None listed