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ClinicalTrials.gov ID

NCT07345325

Lead Sponsor

Nantes University HospitalOTHER

Overall Status

Recruiting

Study Type

Interventional

Phase

Phase 3

Enrollment

422Estimated

Last Update Posted

Jul 28, 2026Actual

Start Date

Jun 11, 2026Actual

Primary Completion Date

Dec 11, 2030Estimated

Completion Date

Jun 11, 2031Estimated

Official Title

Rifampin-free Regimen Versus Rifampin-containing Regimen in the Treatment of Staphylococcal Prosthetic Valve Endocarditis: a Multicenter Randomized Controlled Non-inferiority Study

Brief Summary

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.

Detailed Description

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.

• Infective Endocarditis

• Rifampin-free regimen
• Rifampin containing regimen

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• Definite infective endocarditis according to the 2023 Duke ISCVID criteria or confirmed by the endocarditis team if the endocarditis was classified as possible
• Prosthetic valve endocarditis
• At least one positive blood culture due to Staphylococcus sp (S. aureus or CoNS)
• After the first positive blood culture, at least one negative blood culture (after a minimum of 72 hours of incubation)
• Infective endocarditis due to Staphylococcus sp (S. aureus or coagulase negative staphylococci) susceptible to rifampin
• Antistaphylococcal treatment for endocarditis introduced less than 14 days ago. We do not consider all antibiotic received before the first positive blood culture
• Age ≥ 18-year-old
• Informed, written consent obtained from patient or from patient's near in kin
• Patient insured under a health insurance scheme
• Patient with adequate contraceptive measure

Exclusion Criteria:

• Presence of cardiovascular implanted electronic device with suspected device-related IE without removal of the device
• Expected duration of follow-up <6 months at the time of randomization
• Patient moribund (expected to die in next 48 hours with or without treatment)
• Patients already receiving more than 72 hours of rifampin for the endocarditis treatment prior to randomization
• Positive blood cultures less than 72 hours before randomization
• Medical history of infective endocarditis in the last 3 months
• True allergy to rifampin or a severe intolerance to rifampin
• Contraindication to rifampin
• Patients requiring treatment contraindicated or not recommended with rifampin or incompatible with the inducer effect of rifampicin according to the marketing authorisation.
• ALAT increase greater than 3 times the upper laboratory range
• Extreme weight (< 45 kg or > 150 kg)
• Patients with confirmed prosthetic vascular graft infection or orthopedic-device-related infection
• Patients treated with rifampin for infections other than endocarditis, such as tuberculosis
• Pregnancy or breastfeeding woman
• Inclusion in another drug clinical trial
• Patients who have already been included in the study for a previous episode of endocarditis
• Patients under court protection, guardianship or trusteeship
• Patients who do not speak or understand French language
• Patient unable to collect information in a daily journal
• Patient unable to understand a follow-up by phone contact

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

Nantes University HospitalOTHER

demonchy.e@chu-nice.fr04 92 03 54 67 ext. +33

melanie.lehoux@ch-pau.fr05 59 72 79 57 ext. +33