The primary objective of this study is to demonstrate that a rifampin-free regimen is non-inferior to the rifampin-containing regimen in terms of all-cause mortality in staphylococcal prosthetic valve endocarditis within 6 months after randomization.
A rifampin-based treatment is recommended for prosthetic valve infective endocarditis caused by staphylococcus to act on the biofilm. However, the use of this molecule is associated with numerous adverse effects (digestive disorders, hepatotoxicity, hypersensitivity…) and drug interactions, particularly common in patients with prosthetic valves. In a retrospective study comparing patients receiving antibiotic therapy with rifampin versus without rifampin in staphylococcal prosthetic infective endocarditis (Le Bot et al. CID 2021, PMID: 32706879), there was no difference in terms of mortality or relapse between the two groups, but a longer hospital length of stay in the rifampin-treated group. The aim of this multicentre randomized controlled trial is to demonstrate the non-inferiority of a rifampin-free regimen compared to a rifampin-combined regimen.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
422
Rifampin-free regimen. The choice of other antibiotics is at the discretion of the physicians in charge but should be in accordance with the 2023 ESC guidelines and 2025 French guidelines (AEPEI/SPILF).
Rifampin containing regimen (900 mg/day). Antibiotic treatment of endocarditis in accordance with the 2023 ESC guidelines and 2025 French guidelines.
All-cause mortality rate at 6 months
Deaths of all causes from randomizaton until 6 months
Time frame: Up to 6 months
Microbiological failure
Proportions of patients with at least one microbiological failure defined by bacteremia with the primary pathogen obtained during follow-up but before the end of curative treatment.
Time frame: Up to 6 months
Relapse
Proportions of patients with at least one relapse defined by bacteremia with the primary pathogen obtained during follow-up after the end of treatment of endocarditis until 6 months, then until 12 months.
Time frame: Up to 12 months
Clinically evident embolic event
Proportions of patients with at least one clinically evident embolic event (defined as secondary osteoarticular, splenic, brain or other symptomatic localizations) from randomization until 6 months.
Time frame: Up to 6 months
Valvular surgery
Proportions of patients with at least one valvular surgery at 6 months and at 12 months
Time frame: Up to 12 months
Clinical failure
Proportions of patients with clinical failure (defined by a composite criterion: all-cause mortality or microbiological failure or relapse or embolic event or valvular surgery) at 6 months.
Time frame: Up to 6 months
Time to clinical failure
Time between randomization and occurence of a clinical failure
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CH metropole Savoie, Chambery, GHT Savoie-Belley, Site Aix les Bains
Aix-les-Bains, France
CHU Angers
Angers, France
CHU Besançon
Besançon, France
CHU Bordeaux, Cardiologic hospital of Haut lévêque
Bordeaux, France
CHU Bordeaux, Haut Lévêque Hospital, Infectious disease department
Bordeaux, France
CHU Brest
Brest, France
AP-HP, Groupe hospitalier Henri Mondor
Créteil, France
CHU Dijon Bourgogne
Dijon, France
CHU Grenoble
Grenoble, France
CHD Vendée
La Roche-sur-Yon, France
...and 21 more locations
Time frame: Up to 6 months
Adverse events
Proportions of patients with at least one adverse event grade III or IV related to treatment
Time frame: Up to 6 months
Bleeding complications
Proportions of patients with at least one bleeding complication
Time frame: Up to 6 months
Lenght of stay in hospital
Lenght of stay in hospital
Time frame: Up to 6 months
Duration of curative antibiotic treatment for endocarditis
Duration of curative antibiotic treatment for endocarditis
Time frame: Up to 6 months
All-cause mortality rate at discharge, at 3 and at 12 months
Deaths of all causes from randomization until discharge, then until 3 months and then until 12months
Time frame: Up to 12 months
Readmission in hospitals
Proportions of patients with at least one readmission in hospital (whatever the reason).
Time frame: Up to 12 months
Reclassification of relapse or microbiological failure as reinfection.
Proportions of patients with reclassification of relapse or microbiological failure as reinfection. To determine the proportion of relapses or microbiological failures that are in fact reinfections, the genome of the strain isolated at the time of the suspected microbiological failure or relapse will be compared with the genome of the strain isolated at the time of the initial infection. This will be performed by the national reference center for staphylococci based in Lyon CHU.
Time frame: Up to 12 months
Cost-Effectiveness ratio
Incremental cost-effectiveness ratio (cost per quality-adjusted life year (QALYs) gained)
Time frame: Up to 12 months