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Comparing Rifabutin and Rifampicin for Staphylococcal Joint Infections

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

Phase 3 Interventional Tourcoing Hospital · NCT04672525

This study is testing whether rifabutin is as effective and safer than rifampicin for treating joint infections caused by staph bacteria in patients who have had surgery and are on antibiotics.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment436 (estimated)
Ages18 Years and up
SexAll
SponsorTourcoing Hospital Academic / other
Locations30 sites (Amiens and 29 other locations)
Trial IDNCT04672525 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to compare the effectiveness and safety of rifabutin versus rifampicin in treating prosthetic joint infections (PJIs) caused by staphylococcal bacteria. The study will involve patients who have undergone debridement and are receiving antibiotic therapy while retaining their prosthesis. The hypothesis is that rifabutin may provide similar efficacy to rifampicin but with a better safety profile, particularly regarding drug interactions and liver health. Participants will be monitored to assess the non-inferiority of rifabutin in this context.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with hip or knee prosthetic joint infections treated with the DAIR strategy.

Not a fit: Patients with infections not caused by staphylococcal species or those who cannot tolerate either antibiotic may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a safer alternative antibiotic for patients with staphylococcal PJIs.

How similar studies have performed: While rifampicin is a standard treatment, the use of rifabutin for this specific indication is less common, making this approach relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Amiens and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Prosthetic Infection
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.