Clinical trial NCT05902221: Impact of Rifampicin in Treatment Outcome of Cutibacterium Acnes Prosthetic Joint Infections
Official title: Impact of Rifampicin in Treatment Outcome of Cutibacterium Acnes Prosthetic Joint Infections
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Infections Joint Prosthetic
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2023-06-13
Enrollment: 235
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized two-arm (parallel) comparative open-label cohort clinical trial.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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);

Primary outcomes:
measure: Rate of C. acnes prosthetic joint infections management failure
timeFrame: 24 months after the end of antibiotic treatment
measure: Rate of adverse event linked to rifampicin
timeFrame: during rifampicin treatment
Secondary outcomes:
measure: Rate of C. acnes prosthetic joint infections probable failure
timeFrame: 24 months after the end of antibiotic treatment
measure: Rate of C. acnes prosthetic joint infections management failure
timeFrame: 24 months after the end of antibiotic treatment
measure: Rate of C. acnes prosthetic joint infections management failure
timeFrame: 12 months after the end of antibiotic treatment
Other outcomes:
Locations:
city: Annecy
country: France
facility: CH Annecy Genevois
city: Bordeaux
country: France
facility: CHU de BORDEAUX
city: Lyon
country: France
facility: HCL
city: Marseille
country: France
facility: AP-HM
city: Montpellier
country: France
facility: CHU de MONTPELLIER
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de NICE
city: Paris
country: France
facility: Dianonesses croix saint simon
city: Rennes
country: France
facility: CHU de Rennes
city: Toulouse
country: France
facility: CHU Toulouse
city: Tourcoing
country: France
facility: Ch Tourcoing
city: Tours
country: France
facility: CHRU Tours
Study officials:
References: