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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• All-cause mortality rate at 6 months [Срок оценки: Up to 6 months]

Вторичные конечные точки (12)

• Microbiological failure [Срок оценки: Up to 6 months]
• Relapse [Срок оценки: Up to 12 months]
• Clinically evident embolic event [Срок оценки: Up to 6 months]
• Valvular surgery [Срок оценки: Up to 12 months]
• Clinical failure [Срок оценки: Up to 6 months]
• Time to clinical failure [Срок оценки: Up to 6 months]
• Adverse events [Срок оценки: Up to 6 months]
• Bleeding complications [Срок оценки: Up to 6 months]
• Lenght of stay in hospital [Срок оценки: Up to 6 months]
• Duration of curative antibiotic treatment for endocarditis [Срок оценки: Up to 6 months]
• All-cause mortality rate at discharge, at 3 and at 12 months [Срок оценки: Up to 12 months]
• Readmission in hospitals [Срок оценки: Up to 12 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 31 центр

• CH metropole Savoie, Chambery, GHT Savoie-Belley, Site Aix les Bains — Aix-les-Bains
• CHU Angers — Angers
• CHU Besançon — Besançon
• CHU Bordeaux, Cardiologic hospital of Haut lévêque — Bordeaux
• CHU Bordeaux, Haut Lévêque Hospital, Infectious disease department — Bordeaux
• CHU Brest — Brest
• AP-HP, Groupe hospitalier Henri Mondor — Créteil
• CHU Dijon Bourgogne — Dijon
• … и ещё 23 центра

Идентификаторы

NCT: NCT07345325 · RC24_0404 · 2024-518018-22-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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