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

NCT05902221 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 21-APN-02
• Study Type: interventional
• Target: 235
• Locations: 1 country
• Sites: 12

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.

Conditions

Infections Joint Prosthetic

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Rate of C. acnes prosthetic joint infections probable failure

  24 months after the end of antibiotic treatment

• Rate of C. acnes prosthetic joint infections management failure

  24 months after the end of antibiotic treatment

• Rate of C. acnes prosthetic joint infections management failure

  12 months after the end of antibiotic treatment

Study Arms (2)

Antibiotic treatment backbone alone

ACTIVE COMPARATOR

Amoxicillin or moxifloxacin to the investigator's discretion

Drug: amoxicillin or moxifloxacin

Antibiotic treatment backbone + rifampicin

EXPERIMENTAL

Amoxicillin or moxifloxacin to the investigator's discretion + RIMACTAN

Drug: amoxicillin or moxifloxacin + rifampicin

Interventions

amoxicillin or moxifloxacin DRUG

Antibiotic treatment back bone during 12 weeks

Antibiotic treatment backbone alone

amoxicillin or moxifloxacin + rifampicin DRUG

Antibiotic treatment back bone during 12 weeks + rifampicin

Antibiotic treatment backbone + rifampicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (12)

CH Annecy Genevois

Annecy, France

Location

CHU de BORDEAUX

Bordeaux, France

Location

HCL

Lyon, France

Location

AP-HM

Marseille, France

Location

CHU de MONTPELLIER

Montpellier, France

Location

CHU de Nantes

Nantes, France

Location

CHU de NICE

Nice, 06200, France

Location

Dianonesses croix saint simon

Paris, France

Location

CHU de Rennes

Rennes, France

Location

CHU Toulouse

Toulouse, France

Location

Ch Tourcoing

Tourcoing, France

Location

CHRU Tours

Tours, France

Location

MeSH Terms

Interventions

Amoxicillin; Moxifloxacin; Rifampin

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Central Study Contacts

Johan COURJON, MD

CONTACT

+33(0)492034562; courjon.j@chu-nice.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, randomized two-arm (parallel) comparative open-label cohort clinical trial.

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 13, 2023
• Study Start: March 30, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (12)