Rifabutin Versus Rifampicin for Treatment of Staphylococcal PJI Treated With DAIR
RIFAMAB
1 other identifier
interventional
436
1 country
30
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2021
Longer than P75 for phase_3
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 11, 2020
CompletedFirst Posted
Study publicly available on registry
December 17, 2020
CompletedStudy Start
First participant enrolled
November 8, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
May 10, 2022
May 1, 2022
5 years
October 11, 2020
May 9, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Treatment failure
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
At one year
Secondary Outcomes (7)
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
- +2 more secondary outcomes
Study Arms (2)
RIFAMPICIN
ACTIVE COMPARATORPatient 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.
RIFABUTIN
EXPERIMENTALPatient 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.
Interventions
2 tablets of 150 mg per day rifabutin tablet daily for 12 weeks in 1 administration with a companion treatment
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
CHU Amiens Picardie
Amiens, France
CHU Angers
Angers, France
CHU Besançon
Besançon, France
CH de Béthune
Béthune, France
CHU Bordeaux
Bordeaux, France
APHP Hôpital Ambroise Paré
Boulogne-Billancourt, France
CHRU Brest
Brest, France
CHU Caen
Caen, France
CH Alpes Leman
Contamine-sur-Arve, France
CHU Dijon Bourgogne
Dijon, France
CHU Grenoble Alpes
Grenoble, France
CHRU Lille
Lille, France
GHICL Hôpital Saint Vincent de Paul
Lille, France
CHU de Limoges
Limoges, France
GHICL Hôpital Saint Philibert
Lomme, France
Clinique de la Sauvegarde
Lyon, France
Hospices Civils de Lyon
Lyon, France
APHM Hôpital Nord
Marseille, France
CHU Nice
Nice, France
CH Annecy Genevois
Pringy, France
CH Cornouaille
Quimper, France
CHU Reims
Reims, France
CHU de Rennes
Rennes, France
CHU Saint Etienne
Saint-Priest-en-Jarez, France
CHRU Strasbourg
Strasbourg, France
Hôpital d'instruction des armées Sainte Anne
Toulon, France
Clinique Joseph Ducuing
Toulouse, France
Clinique Médipole Garonne
Toulouse, France
CH Tourcoing
Tourcoing, France
CHRU Tours
Tours, France
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Eric SENNEVILLE, Md PhD
CH TOURCOING
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 11, 2020
First Posted
December 17, 2020
Study Start
November 8, 2021
Primary Completion (Estimated)
November 1, 2026
Study Completion (Estimated)
June 1, 2027
Last Updated
May 10, 2022
Record last verified: 2022-05
Data Sharing
- IPD Sharing
- Will not share