Clinical trial NCT04672525: Rifabutin Versus Rifampicin for Treatment of Staphylococcal PJI Treated With DAIR
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prosthetic Infection
Lead sponsor: Tourcoing Hospital
Sponsor class: OTHER
First posted: 2020-12-17
Enrollment: 436
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Treatment failure
timeFrame: At one year
Secondary outcomes:
measure: Occurrence of serious adverse events (SAEs), including death (i.e. all cause)
timeFrame: At the end of 12 weeks duration of antibiotic treatment planned
measure: Occurrence of any adverse event that could be related to rifampicin or rifabutin
timeFrame: At the end of 12 weeks duration of antibiotic treatment planned
measure: 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
timeFrame: At the end of 12 weeks duration of antibiotic treatment planned
measure: Adherence to antibiotics regimen
timeFrame: At the end of 12 weeks duration of antibiotic treatment planned
measure: Quality of life, as evaluated by EQ 5D 3L questionnaire
timeFrame: At the end of the study follow up, an average of 24 months
measure: Functional prognosis using Oxford questionnaire evolution according to location of PJI
timeFrame: At the end of the study follow up, an average of 24 months
measure: Long term efficacy of rifampicin and rifabutin treatment
timeFrame: At the end of the study follow up, an average of 24 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens Picardie
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: CHU Besançon
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Boulogne-Billancourt
country: France
facility: APHP Hôpital Ambroise Paré
city: Brest
country: France
facility: CHRU Brest
city: Béthune
country: France
facility: CH de Béthune
city: Caen
country: France
facility: CHU Caen
city: Contamine-sur-Arve
country: France
facility: CH Alpes Leman
city: Dijon
country: France
facility: CHU Dijon Bourgogne
city: Grenoble
country: France
facility: CHU Grenoble Alpes
city: Lille
country: France
facility: CHRU Lille
city: Lille
country: France
facility: GHICL Hôpital Saint Vincent de Paul
city: Limoges
country: France
facility: CHU de Limoges
city: Lomme
country: France
facility: GHICL Hôpital Saint Philibert
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: APHM Hôpital Nord
city: Nice
country: France
facility: CHU Nice
city: Pringy
country: France
facility: CH Annecy Genevois
city: Quimper
country: France
facility: CH Cornouaille
city: Reims
country: France
facility: CHU Reims
city: Rennes
country: France
facility: CHU de Rennes
city: Saint-Priest-en-Jarez
country: France
facility: CHU Saint Etienne
city: Strasbourg
country: France
facility: CHRU Strasbourg
city: Toulon
country: France
facility: Hôpital d'instruction des armées Sainte Anne
city: Toulouse
country: France
facility: Clinique Joseph Ducuing
city: Toulouse
country: France
facility: Clinique Médipole Garonne
city: Tourcoing
country: France
facility: CH Tourcoing
city: Tours
country: France
facility: CHRU Tours
Study officials:
affiliation: CH TOURCOING
name: Eric SENNEVILLE, Md PhD
role: PRINCIPAL_INVESTIGATOR
References: