A Phase 3 interventional study of Rifampin-free regimen and Rifampin containing regimen in Infective Endocarditis, sponsored by Nantes University Hospital. Recruiting at 31 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Nantes University Hospital · Phase 3, Interventional, and Treatment
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.
173 studies on the registry are indexed under Endocarditis; 57 are open to participants now.
This study's planned enrollment of 422 is above the median of 92 across 86 interventional studies indexed under Endocarditis.
Browse Endocarditis studies →Nantes University Hospital is the lead sponsor of 839 studies on the registry; 195 are open to participants now.
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Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The experimental arm of the study involves the removal of rifampicin from the antibiotic regimen recommended by the 2023 ESC (European Society of Cardiology) guidelines and the 2025 French guidelines (AEPEI/SPILF) for the treatment of staphylococcal prosthetic valve endocarditis.
Drug: Rifampin-free regimen
Rifampin containing regimen (900 mg/day). Antibiotic treatment of endocarditis in accordance with the 2023 ESC guidelines and the 2025 French guidelines (AEPEI/SPILF).
Drug: Rifampin containing regimen
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
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
Plan to share: Undecided
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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