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AzTrials

Infective EndocarditisPhase 3RIFREENCT07345325

Rifampin-free Regimen Versus Rifampin-containing Regimen in the Treatment of Staphylococcal Prosthetic Valve Endocarditis

A Phase 3 study testing Rifampin-free regimen and Rifampin containing regimen in people with Infective Endocarditis, run by Nantes University Hospital at 31 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Infective Endocarditis
What is being tested?
Rifampin-free regimen and Rifampin containing regimen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
422 participants
Where
31 sitesFrance
Study dates
11 Jun 2026to 11 Jun 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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
  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

31 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Raphaël LECOMTE, MD contact

02 40 08 31 12 ext. +33

raphael.lecomte@chu-nantes.fr

31 sites in 1 country

France31 sites, 31 recruiting

  • CH metropole Savoie, Chambery, GHT Savoie-Belley, Site Aix les Bains

    Aix-les-Bains, 73100

    Emmanuel FORESTIER, MD, 04 79 88 61 61 ext. +33, Emmanuel.Forestier@ch-metropole-savoie.fr

    Recruiting

  • CHU Angers

    Angers, 49933

    Pierre DANNEELS, MD, 02 41 35 53 01 ext. +33, pierre.danneels@chu-angers.fr

    Pierre DANNEELS, MD

    Recruiting

  • CHU Besançon

    Besançon, 25030

    Noémie TISSOT, MD, 03 81 66 81 66 ext. +33, n1tissot@chu-besancon.fr

    Noémie TISSOT, MD

    Recruiting

  • CHU Bordeaux, Cardiologic hospital of Haut lévêque

    Bordeaux, 33600

    Julien TERNACLE, MD, 05 57 65 65 18 ext. +33, julien.ternacle@chu-bordeaux.fr

    Julien TERNACLE, MD

    Recruiting

  • CHU Bordeaux, Haut Lévêque Hospital, Infectious disease department

    Bordeaux, 33600

    05 56 79 56 79 ext. +33, fabrice.camou@chu-bordeaux.fr

    Fabrice CAMOU, MD

    Recruiting

  • CHU Brest

    Brest, 29200

    Scheherazade REZIG, MD, 02 30 33 76 22 ext. +33, scheherazade.rezig@chu-brest.fr

    Scheherazade REZIG, MD

    Recruiting

  • AP-HP, Groupe hospitalier Henri Mondor

    Créteil, 94010

    Raphaël LEPEULE, MD, 01 45 17 80 03 ext. +33, raphael.lepeule@aphp.fr

    Raphaël LEPEULE, MD

    Recruiting

  • CHU Dijon Bourgogne

    Dijon, 21000

    Lionel PIROTH, MD, 03 80 29 33 05 ext. +33, lionel.piroth@chu-dijon.fr

    Lionel PIROTH, MD

    Recruiting

  • CHU Grenoble

    Grenoble, 38043

    Patricia PAVESE, MD, 04 76 76 52 91 ext. +33, PPavese@chu-grenoble.fr

    Patricia PAVESE, MD

    Recruiting

  • CHD Vendée

    La Roche-sur-Yon, 85000

    Thomas GUIMARD, MD, 02 51 44 61 61 ext. +33, thomas.guimard@ght85.fr

    Thomas GUIMARD, MD

    Recruiting

  • CHU Lyon, La Croix-Rousse Hospital, Infective disease department

    Lyon, 69317

    Florent VALOUR, MD, 04 72 07 11 07 ext. +33, florent.valour@chu-lyon.fr

    Florent VALOUR, MD

    Not yet recruiting

  • CHU Lyon, Louis Pradel Hospital, Cardiology Institute

    Lyon, 69677

    Gaultier SEILLIER, MD, 04 72 35 74 51 ext. +33, gaultier.seillier@chu-lyon.fr

    Gaultier SEILLIER, MD

    Not yet recruiting

  • CHU Montpellier

    Montpellier, 34090

    Vincent LE MOING, MD, 04 67 33 67 33 ext. +33, v-le_moing@chu-montpellier.fr

    Vincent LE MOING, MD

    Recruiting

  • CHU Nancy

    Nancy, 54035

    Benjamin LEFEVRE, MD, 03 83 15 40 97 ext. +33, b.lefevre@chru-nancy.fr

    Benjamin LEFEVRE, MD

    Recruiting

  • CHU Nantes, Hôtel Dieu Hospital, Infective disease department

    Nantes, 44093

    Raphaël LECOMTE, MD, 02 40 08 31 12 ext. +33, raphael.lecomte@chu-nantes.fr

    Raphaël LECOMTE, MD

    Recruiting

  • CHU Nantes, Laennec Hospital, Cardiology department

    Nantes, 44800

    Thierry LE TOURNEAU, MD, 02 40 16 54 98 ext. +33, thierry.letourneau@chu-nantes.fr

    Thierry LE TOURNEAU, MD

    Recruiting

  • CHU Nice

    Nice, 06202

    Elisa DEMONCHY, MD, 04 92 03 54 67 ext. +33, demonchy.e@chu-nice.fr

    Elisa DEMONCHY, MD

    Recruiting

  • CHR Orléans

    Orléans, 45067

    Guillaume BERAUD, MD, 02 38 51 44 44 ext. +33, guillaume.beraud@chu-orleans.fr

    Guillaume BERAUD, MD

    Recruiting

  • AP-HP hôpital St Antoine

    Paris, 75012

    Laure SURGERS, MD, 01 49 28 20 00 ext. +33, laure.surgers@aphp.fr

    Laure SURGERS, MD

    Recruiting

  • AP-HP, Hôpital Pitié Salpétrière

    Paris, 75013

    Alexandre BLEIBTREU, MD, 01 42 16 00 00 ext. +33, alexandre.bleibtreu@aphp.fr

    Recruiting

  • AP-HP, hôpital Bichat-Claude Bernard

    Paris, 75018

    Xavier DUVAL, MD, 01 40 25 80 80 ext. +33, xavier.duval@aphp.fr

    Xavier DUVAL, MD

    Recruiting

  • CH Pau

    Pau, 64000

    Mélanie LEHOUX, MD, 05 59 72 79 57 ext. +33, melanie.lehoux@ch-pau.fr

    Mélanie LEHOUX, MD

    Recruiting

  • CHU Poitiers

    Poitiers, 86000

    Jean-Marie TURMEL, MD, 05 49 44 44 44 ext. +33, jean-marie.turmel@chu-poitiers.fr

    Jean-Marie TURMEL, MD

    Recruiting

  • CH intercommunal Cornouaille Quimper

    Quimper, 29000

    Pauline MARTINET, MD, 02 98 52 60 67 ext. +33, pauline.martinet@ch-cornouaille.fr

    Pauline MARTINET, MD

    Recruiting

  • CHU Rennes

    Rennes, 35000

    Audrey LE BOT, MD, 02 99 28 43 21 ext. +33, audrey.le.bot@chu-rennes.fr

    Audrey LE BOT, MD

    Recruiting

  • CHU St-Etienne

    Saint-Etienne, 42270

    Elisabeth BOTELHO-NEVERS, MD, 04 77 49 60 30 ext. +33, elisabeth.botelho-nevers@chu-st-etienne.fr

    Elisabeth BOTELHO-NEVERS, MD

    Recruiting

  • CHU Strasbourg

    Strasbourg, 67000

    Yvon RUCH, MD, 03 69 55 12 19 ext. +33, yvon.ruch@chru-strasbourg.fr

    Yvon RUCH, MD

    Recruiting

  • CHU Toulouse, Purpan Hospital, Infectious disease department

    Toulouse, 31059

    Guillaume MARTIN-BLONDEL, MD, 05 61 77 22 33 ext. +33, martin-blondel.g@chu-toulouse.fr

    Guillaume MARTIN BLONDEL, MD

    Recruiting

  • CHU Toulouse, Rangueil Hospital, Cardiology department

    Toulouse, 31400

    Yoan LAVIE-BADIE, MD, 05 61 32 24 37 ext. +33, lavie-badie.y@chu-toulouse.fr

    Yoan LAVIE-BADIE, MD

    Recruiting

  • CH Tourcoing

    Tourcoing, 59200

    Benoit GACHET, MD, 03 20 69 49 49 ext. +33, senneric670@gmail.com

    Benoit GACHET, MD

    Recruiting

  • CHU Tours

    Tours, 37044

    Adrien LEMAIGNEN, MD, 02 18 37 06 44 ext. +33, adrien.lemaignen@univ-tours.fr

    Adrien LEMAIGNEN, MD

    Recruiting

Other trials in France

About this study

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

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.

Read the 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.

Being tested
Rifampin-free regimen, Rifampin containing regimen
Keywords
infective endocarditis, prosthetic valve, Rifampin, Staphylococcus aureus
Medical subject headings
Endocarditis, Staphylococcal Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rifampin-free regimenDrug

    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 regimenDrug

    Rifampin containing regimen (900 mg/day). Antibiotic treatment of endocarditis in accordance with the 2023 ESC guidelines and 2025 French guidelines.

Study groups in NCT07345325
Study groupRoleWhat they receive
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.
Receives: Drug: Rifampin-free regimen
Rifampin containing regimenActive comparatorRifampin containing regimen (900 mg/day). Antibiotic treatment of endocarditis in accordance with the 2023 ESC guidelines and the 2025 French guidelines (AEPEI/SPILF).
Receives: Drug: Rifampin containing regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. All-cause mortality rate at 6 months

    Deaths of all causes from randomizaton until 6 months

    Measured: Up to 6 months

Secondary outcomes (14)

  1. 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.

    Measured: Up to 6 months

  2. 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.

    Measured: Up to 12 months

  3. 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.

    Measured: Up to 6 months

  4. Valvular surgery

    Proportions of patients with at least one valvular surgery at 6 months and at 12 months

    Measured: Up to 12 months

  5. 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.

    Measured: Up to 6 months

  6. Time to clinical failure

    Time between randomization and occurence of a clinical failure

    Measured: Up to 6 months

  7. Adverse events

    Proportions of patients with at least one adverse event grade III or IV related to treatment

    Measured: Up to 6 months

  8. Bleeding complications

    Proportions of patients with at least one bleeding complication

    Measured: Up to 6 months

  9. Lenght of stay in hospital

    Lenght of stay in hospital

    Measured: Up to 6 months

  10. Duration of curative antibiotic treatment for endocarditis

    Duration of curative antibiotic treatment for endocarditis

    Measured: Up to 6 months

  11. 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

    Measured: Up to 12 months

  12. Readmission in hospitals

    Proportions of patients with at least one readmission in hospital (whatever the reason).

    Measured: Up to 12 months

  13. 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.

    Measured: Up to 12 months

  14. Cost-Effectiveness ratio

    Incremental cost-effectiveness ratio (cost per quality-adjusted life year (QALYs) gained)

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jan 2026
  2. Study start11 Jun 2026
  3. Primary completion11 Dec 2030 (estimated)
  4. Study completion11 Jun 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
422 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07345325
Sponsor's protocol ID
RC24_0404
Other IDs
2024-518018-22-00
Acronym
RIFREE
Status last verified
Oct 2026
First submitted
12 Dec 2025
Last updated
21 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rifampin-free regimen and Rifampin containing regimen in people with Infective Endocarditis, run by Nantes University Hospital at 31 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Raphaël LECOMTE, MD (02 40 08 31 12 ext. +33, raphael.lecomte@chu-nantes.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-cause mortality rate at 6 months (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07345325.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.

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