RIFAMAB : Rifabutin versus rifampicin, staphylococcal prosthetic joint infection, multicenter randomized, open-label, non-inferiority trial

Phase 3

Not yet recruiting

• Conditions: Adult with an staphylococcal prosthetic joint infection treated with debridement, antibiotics and implant retention (DAIR strategy)

• Registration Number: 2024-519894-20-01
• Lead Sponsor: Centre Hospitalier De Tourcoing

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2025-02-07
• Last Update Posted: 2025-02-07

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 436

Inclusion Criteria

Hip or knee Prosthetic joint infection treated by debridement, antibiotic therapy initiation and retention of prothesis (DAIR strategy)

Microbiologically documented infection corresponds to the isolation of staphylococcus aureus or coagulase-negative Staphylococcus aureus from reliable samples: intraoperatively (≥ 3 during synovectomywashing), joint puncture or blood culture; the microorganism(s) will be considered pathogenic if identified in ≥ 2 reliable samples.

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.

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.

Exclusion Criteria

Known or suspected malabsorption (imperfect absorption of food material by the small intestine)

Ongoing treatment that contraindicates the use of rifampicin or rifabutine

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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		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

Secondary Outcome Measures

Name	Time	Method
Proportion of patient which are free from SAEs occurrence, as defined by: o 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.		Proportion of patient which are free from SAEs occurrence, as defined by: o 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.
Number and rate of patients in each arm who experiences: o Liver cytolysis (>=2N for ALT AND/OR AST) o Acute Kidney failure as defined by serum creatinine increase in KDIGO o Digestive symptoms, including diarrhea o Who required a modification of antibiotic dosage during the 12 weeks’ period of antibiotic treatment o Uveitis/ophthalmologic disorder o Neurological disorder		Number and rate of patients in each arm who experiences: o Liver cytolysis (>=2N for ALT AND/OR AST) o Acute Kidney failure as defined by serum creatinine increase in KDIGO o Digestive symptoms, including diarrhea o Who required a modification of antibiotic dosage during the 12 weeks’ period of antibiotic treatment o Uveitis/ophthalmologic disorder o Neurological disorder
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.		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 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.		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.
Quality of life, as evaluated by the use EQ5D5L auto-questionnaire at week 6, month 6, month 12 and month 24 as used in previous randomized clinical trial on bone and joint infection.		Quality of life, as evaluated by the use EQ5D5L auto-questionnaire at week 6, month 6, month 12 and month 24 as used in previous randomized clinical trial on bone and joint infection.
Oxford Hip and Knee Scores evolution between week 6, month 6, month 12 and month 24 as used in previous randomized clinical trial on bone and joint infection.		Oxford Hip and Knee Scores evolution between week 6, month 6, month 12 and month 24 as used in previous randomized clinical trial on bone and joint infection.
Long term efficacy: treatment failure, as defined for primary outcome, occurring between 12 months and 24 months after initial surgery.		Long term efficacy: treatment failure, as defined for primary outcome, occurring between 12 months and 24 months after initial surgery.

Trial Locations

Locations (33)

Assistance Publique Hopitaux De Paris; 🇫🇷 Paris, France

Centre Hospitalier Annecy Genevois; 🇫🇷 Epagny Metz Tessy, France

HPM Nord; 🇫🇷 Lille, France

Centre Hospitalier De Perpignan; 🇫🇷 Perpignan Cedex, France

Centre Hospitalier Regional Universitaire; 🇫🇷 Besancon Cedex, France

Centre Hospitalier De Colmar; 🇫🇷 Colmar Cedex, France

Groupement Des Hopitaux De L'Institut Catholique De Lille; 🇫🇷 Lille, France

Centre Hospitalier Universitaire De Dijon; 🇫🇷 Dijon, France

Centre Hospitalier Universitaire Rouen; 🇫🇷 Rouen, France

Centre Hospitalier Universitaire D'Angers; 🇫🇷 Angers, France

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Assistance Publique Hopitaux De Paris

🇫🇷Paris, France

Aurélien Dinh

Site contact

0147107760

aurelien.dinh@aphp.fr

Anne-Lise Munier

Site contact

0145956339

anne-lise.munier@aphp.fr

Laure Surgers

Site contact

0149280939

laure.surgers@aphp.fr