Rifabutin Versus Rifampicin for Treatment of Staphylococcal Prosthetic Joint Infection Treated With Debridement, Antibiotics and Implant Retention (DAIR Strategy): a Multicenter Randomized, Open-label, Non-inferiority Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 436
- 试验地点
- 30
- 主要终点
- Treatment failure
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hip or knee Prosthetic joint infection treated by debridement, antibiotic therapy initiation and retention of prothesis (DAIR strategy)
- •Infected with at least one of the following microorganisms:
- •Staphylococcus aureus
- •Coagulase-negative staphylococci
- •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.
- •Age ≥ 18 years
- •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.
- •Signed Inform consent
- •Patient having the rights to French social insurance
- •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
排除标准
- •Suspicion of reduce absorption of oral treatment due to abdominal disorder Known or suspected malabsorption (imperfect absorption of food material by the small intestine)
- •Polymicrobial infection due to other than staphylococcus species susceptible to rifampicin
- •Known or suspected allergy to rifabutin and/or rifampicin
- •Diagnosis of endocarditis associated to PJI
- •Renal transplant or Chronic kidney disease with an eGFR of less than 30ml/min/1.73m²
- •Other Solid Organ Transplant
- •Liver cirrhosis, Child-Pugh score C
- •Any other concomitant infection which required a prolonged course of intravenous antibiotic therapy
- •Oestroprogestative-based contraception
- •Oral anticoagulant drugs
- •Other drug-drug interaction that contraindicated rifampicin or rifabutin
- •Unable to take oral treatment
- •Receive empirical postoperative antibiotic treatment by rifampicin or rifabutin prior to randomization
- •Pregnancy or lactating women
- •Curator or guardianship or patient placed under judicial protection
- •Participation in other interventional research during the study
研究组 & 干预措施
RIFAMPICIN
Patient with staphylococcal PJI, treated with DAIR strategy, and randomized in the control group will receive rifampicin in association with another antibiotic except rifabutin, as-per recommendations for 12 weeks.
干预措施: Rifampicin (Drug)
RIFABUTIN
Patient with staphylococcal PJI treated with DAIR strategy, and randomized in the experimental group, will receive rifabutin in association with another antibiotic except rifampicin, as-per recommendations for 12 weeks.
干预措施: Rifabutin (Drug)
结局指标
主要结局
Treatment failure
时间窗: 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
次要结局
- Occurrence of serious adverse events (SAEs), including death (i.e. all cause)(At the end of 12 weeks duration of antibiotic treatment planned)
- Occurrence of any adverse event that could be related to rifampicin or rifabutin(At the end of 12 weeks duration of antibiotic treatment planned)
- 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)
- Adherence to antibiotics regimen(At the end of 12 weeks duration of antibiotic treatment planned)
- Quality of life, as evaluated by EQ 5D 3L questionnaire(At the end of the study follow up, an average of 24 months)
- Functional prognosis using Oxford questionnaire evolution according to location of PJI(At the end of the study follow up, an average of 24 months)
- Long term efficacy of rifampicin and rifabutin treatment(At the end of the study follow up, an average of 24 months)