Efficacy and Safety of Ampicillin and Ceftriaxone Continuous Infusion Versus Standard Therapy for the Treatment of Enterococcus Faecalis Infective Endocarditis (DOβLEI Study)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 284
- 试验地点
- 18
- 主要终点
- Clinical failure
研究概览
简要总结
Phase IV, open-label, randomized and multicenter clinical trial to prove that patients with Enterococcus faecalis infective endocarditis treated with an antibiotic treatment as a continuous infusion is non-inferior to the standard treatment, usually administered in hospitalized patients.
详细描述
The aim of the study is to prove that the continuous infusion of antibiotic treatment for the patients with Enterococcus faecalis infective endocarditis is as effective and safe as the standard treatment. The continuous infusion modality of treatment is expected to provide numerous benefits for individual patients, global health, and for the National Health Care System by reducing to hospital stays from 4-6 weeks to approximately 2-3 weeks and hospital-driven complications.
The mortality, rate of serious adverse events, total number of days of antibiotic treatment and days of hospitalization, among others, are included as secondary objectives.
This is a pragmatic study as the number or visits performed for the study are similar to the normal clinical follow-up for this patients. Final contact and final visit for the study will be performed at 365 days after the 42 days of treatment.
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
- •Adult patients
- •Possible or definitive diagnosis of infective endocarditis due to Enterococcus faecalis
- •Signed informed consent of patients
排除标准
- •Allergy to penicillins or cephalosporins
- •Pregnancy and lactation
- •Polymicrobial infection including microorganisms different to E. faecalis
研究组 & 干预措施
Continuous intravenous antibiotic infusion
Ampicillin 12g/24h plus ceftriaxone 4g/12h continuous infusion. The duration of treatment will be 42 days.
干预措施: Ampicillin plus ceftriaxone in continuous infusion (Drug)
Standard treatment
Ampicillin 2g/4h plus ceftriaxone 2g/12h intermittent infusion for a minimum of 14 days. Starting on day 14 of treatment, if the patient is discharged from the hospital, the following treatments will be permitted:
-
Intravenous treatment in TADE programs according to the following regimens:
-
Ampicillin 2g/4h plus ceftriaxone 2g/12h as an intermittent infusion
-
Teicoplanin 10-12mg/kg/24h
-
Daptomycin 10-12mg/kg/24h
-
Dalbavancin: Initial dose: 2 doses of 1500mg every 2 weeks. Maintenance dose: 1500mg every 15days.
-
Linezolid: 600mg/12hours
-
Oral treatment according to the following regimens:
-
Amoxicillin 1 g/6h + Moxifloxacin 400mg/24h.
-
Amoxicillin 1 g/6h + Linezolid 600 mg/12h.
-
Amoxicillin 1 g/6h + Rifampin 600 mg/12h.
-
Linezolid 600 mg/12h + Moxifloxacin 400mg/24h.
-
Linezolid 600 mg/12h + Rifampin 600 mg/12h. The duration of treatment will be 42 days
干预措施: Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed (Drug)
结局指标
主要结局
Clinical failure
时间窗: One year after the end of the treatment
It is defined as follow: i) Confirmed recurrence of E. faecalis infective endocarditis, ii) all-cause mortality. A composite primary endpoint has been chosen to include both a very clinically relevant variable and a hard variable such as survival
次要结局
- Therapeutic failure(Up to 12 months after treatment administration)
- Cardiac surgeries(Up to 12 months after treatment administration)
- Adverse events(From randomisation until 30 days after the last dose administration)
- Antibiotic treatment days(Up to 12 months after treatment administration)
- Healthcare-associated infections(Up to 12 months after treatment administration)
- Recurrence(Up to 12 months after treatment administration)
- Pharmacokinetic parameters(Day 14)
- Readmissions(Up to 12 months after treatment administration)
- Outpatient Parenteral Antimicrobial Therapy(Up to 12 months after treatment administration)
- Minimum free serum concentration(Day 14)
- Minimum Inhibitory Concentration(Day 14)
- Steady-state plasma concentration(Day 14)