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

Phase 3

Not yet recruiting

• Conditions: Infections Joint Prosthetic
• Interventions: Drug: amoxicillin or moxifloxacin + rifampicin; Drug: amoxicillin or moxifloxacin

• Registration Number: NCT05902221
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-06-05
• Study First Submitted QC: 2023-06-05
• Study First Posted: 2023-06-13
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-12
• Last Update Posted: 2024-03-13
• Study Start: 2024-03-30
• Primary Completion: 2027-07-01
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 235

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);

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antibiotic treatment backbone + rifampicin	amoxicillin or moxifloxacin + rifampicin	Amoxicillin or moxifloxacin to the investigator's discretion + RIMACTAN
Antibiotic treatment backbone alone	amoxicillin or moxifloxacin	Amoxicillin or moxifloxacin to the investigator's discretion

Primary Outcome Measures

Name	Time	Method
Rate of C. acnes prosthetic joint infections management failure	24 months after the end of antibiotic treatment	Defined by Relapse, New infection, early failure
Rate of adverse event linked to rifampicin	during rifampicin treatment	adverse events will be described by frequency and grade, throughout the treatment (classified according to the CTCAE 5.0.)

Secondary Outcome Measures

Name	Time	Method
Rate of C. acnes prosthetic joint infections probable failure	24 months after the end of antibiotic treatment	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
Rate of C. acnes prosthetic joint infections management failure	12 months after the end of antibiotic treatment	Defined by Relapse, New infection, early failure

Trial Locations

Locations (12)

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, France