Rifabutin Versus Rifampicin for Treatment of Staphylococcal PJI Treated With DAIR

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Rifabutin
  2 tablets of 150 mg per day rifabutin tablet daily for 12 weeks in 1 administration with a companion treatment
• Препарат Rifampicin
  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

Первичные конечные точки

• Treatment failure [Срок оценки: At one year]

Вторичные конечные точки (7)

• Occurrence of serious adverse events (SAEs), including death (i.e. all cause) [Срок оценки: At the end of 12 weeks duration of antibiotic treatment planned]
• Occurrence of any adverse event that could be related to rifampicin or rifabutin [Срок оценки: 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 [Срок оценки: At the end of 12 weeks duration of antibiotic treatment planned]
• Adherence to antibiotics regimen [Срок оценки: At the end of 12 weeks duration of antibiotic treatment planned]
• Quality of life, as evaluated by EQ 5D 3L questionnaire [Срок оценки: At the end of the study follow up, an average of 24 months]
• Functional prognosis using Oxford questionnaire evolution according to location of PJI [Срок оценки: At the end of the study follow up, an average of 24 months]
• Long term efficacy of rifampicin and rifabutin treatment [Срок оценки: At the end of the study follow up, an average of 24 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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
• Porphyria
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 30 центров

• CHU Amiens Picardie — Amiens
• CHU Angers — Angers
• CHU Besançon — Besançon
• CH de Béthune — Béthune
• CHU Bordeaux — Bordeaux
• APHP Hôpital Ambroise Paré — Boulogne-Billancourt
• CHRU Brest — Brest
• CHU Caen — Caen
• … и ещё 22 центра

Идентификаторы

NCT: NCT04672525 · RIPH_2019_01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗