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

Study Overview
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Brief Summary
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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.

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

Conditions
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Infections Joint Prosthetic

Intervention / Treatment
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* Drug: amoxicillin or moxifloxacin
* Drug: amoxicillin or moxifloxacin + rifampicin


Participation Criteria
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Eligibility Criteria
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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);

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, randomized two-arm (parallel) comparative open-label cohort clinical trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antibiotic treatment backbone alone<br>Amoxicillin or moxifloxacin to the investigator's discretion | Drug: amoxicillin or moxifloxacin<br>* Antibiotic treatment back bone during 12 weeks<br>|
| Experimental: Antibiotic treatment backbone + rifampicin<br>Amoxicillin or moxifloxacin to the investigator's discretion + RIMACTAN | Drug: amoxicillin or moxifloxacin + rifampicin<br>* Antibiotic treatment back bone during 12 weeks + rifampicin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of C. acnes prosthetic joint infections management failure | Defined by Relapse, New infection, early failure | 24 months after the end of antibiotic treatment | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Rate of C. acnes prosthetic joint infections management failure | Defined by Relapse, New infection, early failure | 24 months after the end of antibiotic treatment | 
| Rate of C. acnes prosthetic joint infections management failure | Defined by Relapse, New infection, early failure | 12 months after the end of antibiotic treatment |