Rifampin-free Regimen Versus Rifampin-containing Regimen in the Treatment of Staphylococcal Prosthetic Valve Endocarditis: a Multicenter Randomized Controlled Non-inferiority Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 422
- 试验地点
- 43
- 主要终点
- All-cause mortality rate at 6 months
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Rifampin-free regimen.
The 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.
干预措施: Rifampin-free regimen (Drug)
Rifampin containing regimen
Rifampin containing regimen (900 mg/day). Antibiotic treatment of endocarditis in accordance with the 2023 ESC guidelines and the 2025 French guidelines (AEPEI/SPILF).
干预措施: Rifampin containing regimen (Drug)
结局指标
主要结局
All-cause mortality rate at 6 months
时间窗: Up to 6 months
Deaths of all causes from randomizaton until 6 months
次要结局
- 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)
- Time to clinical failure(Up to 6 months)
- Adverse events(Up to 6 months)
- Bleeding complications(Up to 6 months)
- Lenght of stay in hospital(Up to 6 months)
- Duration of curative antibiotic treatment for endocarditis(Up to 6 months)
- All-cause mortality rate at discharge, at 3 and at 12 months(Up to 12 months)
- Readmission in hospitals(Up to 12 months)
- Reclassification of relapse or microbiological failure as reinfection.(Up to 12 months)
- Cost-Effectiveness ratio(Up to 12 months)