Rifampin-free Regimen Versus Rifampin-containing Regimen in the Treatment of Staphylococcal Prosthetic Valve Endocarditis
RIFREE
2 other identifiers
interventional
422
1 country
31
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2026
Longer than P75 for phase_3
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 12, 2025
CompletedFirst Posted
Study publicly available on registry
January 15, 2026
CompletedStudy Start
First participant enrolled
June 11, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 11, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 11, 2031
July 28, 2026
July 1, 2026
4.5 years
December 12, 2025
July 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
All-cause mortality rate at 6 months
Deaths of all causes from randomizaton until 6 months
Up to 6 months
Secondary Outcomes (14)
Microbiological failure
Up to 6 months
Relapse
Up to 12 months
Clinically evident embolic event
Up to 6 months
Valvular surgery
Up to 12 months
Clinical failure
Up to 6 months
- +9 more secondary outcomes
Study Arms (2)
Rifampin-free regimen.
EXPERIMENTALThe 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.
Rifampin containing regimen
ACTIVE COMPARATORRifampin containing regimen (900 mg/day). Antibiotic treatment of endocarditis in accordance with the 2023 ESC guidelines and the 2025 French guidelines (AEPEI/SPILF).
Interventions
Rifampin containing regimen (900 mg/day). Antibiotic treatment of endocarditis in accordance with the 2023 ESC guidelines and 2025 French guidelines.
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).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- Patients who have already been included in the study for a previous episode of endocarditis
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
CH metropole Savoie, Chambery, GHT Savoie-Belley, Site Aix les Bains
Aix-les-Bains, 73100, France
CHU Angers
Angers, 49933, France
CHU Besançon
Besançon, 25030, France
CHU Bordeaux, Cardiologic hospital of Haut lévêque
Bordeaux, 33600, France
CHU Bordeaux, Haut Lévêque Hospital, Infectious disease department
Bordeaux, 33600, France
CHU Brest
Brest, 29200, France
AP-HP, Groupe hospitalier Henri Mondor
Créteil, 94010, France
CHU Dijon Bourgogne
Dijon, 21000, France
CHU Grenoble
Grenoble, 38043, France
CHD Vendée
La Roche-sur-Yon, 85000, France
CHU Lyon, La Croix-Rousse Hospital, Infective disease department
Lyon, 69317, France
CHU Lyon, Louis Pradel Hospital, Cardiology Institute
Lyon, 69677, France
CHU Montpellier
Montpellier, 34090, France
CHU Nancy
Nancy, 54035, France
CHU Nantes, Hôtel Dieu Hospital, Infective disease department
Nantes, 44093, France
CHU Nantes, Laennec Hospital, Cardiology department
Nantes, 44800, France
CHU Nice
Nice, 06202, France
CHR Orléans
Orléans, 45067, France
AP-HP hôpital St Antoine
Paris, 75012, France
AP-HP, Hôpital Pitié Salpétrière
Paris, 75013, France
AP-HP, hôpital Bichat-Claude Bernard
Paris, 75018, France
CH Pau
Pau, 64000, France
CHU Poitiers
Poitiers, 86000, France
CH intercommunal Cornouaille Quimper
Quimper, 29000, France
CHU Rennes
Rennes, 35000, France
CHU St-Etienne
Saint-Etienne, 42270, France
CHU Strasbourg
Strasbourg, 67000, France
CHU Toulouse, Purpan Hospital, Infectious disease department
Toulouse, 31059, France
CHU Toulouse, Rangueil Hospital, Cardiology department
Toulouse, 31400, France
CH Tourcoing
Tourcoing, 59200, France
CHU Tours
Tours, 37044, France
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 12, 2025
First Posted
January 15, 2026
Study Start
June 11, 2026
Primary Completion (Estimated)
December 11, 2030
Study Completion (Estimated)
June 11, 2031
Last Updated
July 28, 2026
Record last verified: 2026-07