Impact of Rifampicin in Treatment Outcome of Cutibacterium Acnes Prosthetic Joint Infections

Infections Joint Prosthetic Clinical Trial

— RIFACute  

Official title:

Impact of Rifampicin in Treatment Outcome of Cutibacterium Acnes Prosthetic Joint Infections

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05902221
• Other study ID #: 21-APN-02
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 30, 2024
• Est. completion date: July 1, 2027

Study information

• Verified date: March 2024
• Source: Centre Hospitalier Universitaire de Nice
• Contact: Johan COURJON, MD
• Phone: +33(0)492034562
• Email: courjon.j[@]chu-nice.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cutibacterium acnes is involved in nearly 40% of shoulder prosthetic joint infections (PJI). After shoulder prothesis, C. acnes mainly affects hip prosthesis. One recent work from the Lyon (France) bone and joint infections reference center with data focusing mainly on hip and knee PJI has reported that C. acnes is the leading cause of late-onset PJI after coagulase negative staphylococci (CNS) (late acute PJI not considered). In such late-onset device-related infection, biofilm, as produced by C. acnes during PJI represents a major hurdle on the path to patient's cure. Because biofilm-associated bacteria have a slower metabolism and a lower multiplication rate than planktonic bacteria, antibiotic susceptibility can be hampered. Rifampicin is an antibiotic with low minimal bactericidal concentration against S. aureus and CNS biofilm-associated bacteria8 which significantly influence patient's outcome during staphylococci PJI.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 235
• Est. completion date: July 1, 2027
• Est. primary completion date: July 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age: > or =18 years old;
• Monomicrobial, rifampicin susceptible Cutibacterium acnes late total knee arthroplasty (TKA) or hip arthroplasty (total, THA or hemiarthroplasty, HH) or shoulder arthroplasty (total, TSA or hemiarthroplasty, SH) infection treated surgically with single-stage or two-stage revision;
• Isolation of C. acnes on two distinct per-operative samples collected during the single-stage or the two-stage revision
• Based on the antimicrobial susceptibility test of the C. acnes and the medical history of the patient, the PJI can be treated with amoxicillin or moxifloxacin;
• Women considered of childbearing potential (WOCBP) requires use of a highly effective contraceptive measure as intrauterine device (IUD), intrauterine hormone-releasing system (IUS), documented bilateral tubal occlusion, documented vasectomised partner, sexual abstinence. Contraception should be maintained during treatment and until the end of relevant systemic exposure.

Exclusion Criteria:

• Contraindication to Rifampicin (included ongoing treatment contraindicated with rifampicin)
• Contraindication to Amoxicillin AND moxifloxacin (included ongoing treatment contraindicated with these medicines)
• Empirical antibiotic treatment not administered during the 24 hours following revision surgery;
• Inactive empirical antibiotic treatment following surgery according to the AST of the bacteria;
• disease-modifying treatment incompatible with the inducer effect of rifampicin
• Liver cirrhosis;
• Pregnancy: a pregnancy blood test will be performed on all women of childbearing age. The results will be sent to the patient by the doctor of their choice;
• Porphyria;
• Renal insufficiency with GFR < 30ml/min/1.73 m2 (CKD-EPI);

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Infections Joint Prosthetic

Intervention

Drug:
• amoxicillin or moxifloxacin
Antibiotic treatment back bone during 12 weeks
• amoxicillin or moxifloxacin + rifampicin
Antibiotic treatment back bone during 12 weeks + rifampicin

Locations

Country	Name	City	State
France	CH Annecy Genevois	Annecy
France	CHU de BORDEAUX	Bordeaux
France	HCL	Lyon
France	AP-HM	Marseille
France	CHU de MONTPELLIER	Montpellier
France	CHU de Nantes	Nantes
France	CHU de NICE	Nice
France	Dianonesses croix saint simon	Paris
France	CHU de Rennes	Rennes
France	CHU Toulouse	Toulouse
France	Ch Tourcoing	Tourcoing
France	CHRU Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nice

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of C. acnes prosthetic joint infections management failure	Defined by Relapse, New infection, early failure	24 months after the end of antibiotic treatment
Primary	Rate of adverse event linked to rifampicin	adverse events will be described by frequency and grade, throughout the treatment (classified according to the CTCAE 5.0.)	during rifampicin treatment
Secondary	Rate of C. acnes prosthetic joint infections probable failure	prosthetic joint infections probable failure suspected in case of specific clinical signs (fistula) and/or inflammatory synovial fluid without microbiological positive results and/or histopathological results after revision without microbiological positive results	24 months after the end of antibiotic treatment
Secondary	Rate of C. acnes prosthetic joint infections management failure	Defined by Relapse, New infection, early failure	24 months after the end of antibiotic treatment
Secondary	Rate of C. acnes prosthetic joint infections management failure	Defined by Relapse, New infection, early failure	12 months after the end of antibiotic treatment