Rifampin-free therapy vs rifampin-containing therapy for staphylococcal prosthetic valve endocarditis

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This multicenter Phase 3 randomized trial compares a rifampin-free regimen to a rifampin-containing regimen in adults with Prosthetic Valve Endocarditis caused by Staphylococcus species. The primary goal is to show non-inferiority in all-cause mortality within 6 months of randomization. Eligible participants have definite infective endocarditis with a prosthetic valve, a positive Staphylococcus blood culture, and recent antistaphylococcal therapy, among other criteria. The study addresses rifampin-associated adverse effects and drug interactions by evaluating outcomes without rifampin. Results will inform whether rifampin can be safely omitted without compromising survival. Early retrospective data suggested no mortality difference but longer hospitalization with rifampin, prompting this controlled trial.

Why it matters

Who can join: the full rules

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

Where it's running

• CH metropole Savoie, Chambery, GHT Savoie-Belley, Site Aix les Bains
  Aix-les-Bains, France Recruiting
• CHU Angers
  Angers, France Recruiting
• CHU Besançon
  Besançon, France Recruiting
• CHU Bordeaux, Cardiologic hospital of Haut lévêque
  Bordeaux, France Recruiting
• CHU Bordeaux, Haut Lévêque Hospital, Infectious disease department
  Bordeaux, France Recruiting
• CHU Brest
  Brest, France Recruiting

Study contacts

• Study coordinator: Raphaël LECOMTE, MD
• Email: raphael.lecomte@chu-nantes.fr
• Phone: 02 40 08 31 12

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.