Impact of Rifampicin in Treatment Outcome of Cutibacterium Acnes Prosthetic Joint Infections (RIFACute)

Centre Hospitalier Universitaire de Nice

Status and phase: Not yet enrolling; Phase 3

Conditions: Infections Joint Prosthetic

Treatments: Drug: amoxicillin or moxifloxacin + rifampicin; Drug: amoxicillin or moxifloxacin

Study type: Interventional

Funder types: Other

Identifiers

NCT05902221

21-APN-02

Details and patient eligibility

About

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.

Enrollment: 235 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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);

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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235 participants in 2 patient groups

Antibiotic treatment backbone alone

Active Comparator group

Description:

Amoxicillin or moxifloxacin to the investigator's discretion

Treatment:

Drug: amoxicillin or moxifloxacin

Antibiotic treatment backbone + rifampicin

Experimental group

Description:

Amoxicillin or moxifloxacin to the investigator's discretion + RIMACTAN

Treatment:

Drug: amoxicillin or moxifloxacin + rifampicin