Randomized Non-inferiority Clinical Trial to Evaluate the Effectiveness and Security of Therapy for Non Complicated Enterococcal Bacteremia.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 284
- 试验地点
- 22
- 主要终点
- Clinical success
研究概览
简要总结
Randomized clinical trial to determine the optimal duration of antibiotic treatment for E. Faecalis or E. faecium bacteraemia, following an innovative DOOR / RADAR (Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR)) analysis methodology.
Phase IV clinical trial, open-labelled, randomized, pragmatic, multicenter study to demonstrate non-inferiority of a 7-day antibiotic regimen vs. 14 days in the treatment of bacteremia due to E. faecalis or E. faecium.
详细描述
Phase IV clinical trial, open-labelled, randomized, pragmatic, multicenter study to demonstrate non-inferiority of a 7-day antibiotic regimen vs. 14 days in the treatment of bacteremia due to E. faecalis or E. faecium.
Adequate antibiotic regimen is included in the protocol; initially this regimen included ciprofloxacine but this has been modified si that in the last version 3 dated feb 6th ciprofloxacine is not allowed as a possible treatment for these patients.
Antibiotic regimen included as possible treatments in the study are the follows:
- Isolated strains sensitive to ampicillin: ampicillin 2g/6 or 8h (i.v)
- Strains resistant to ampicillin and/or patients with allergy to beta-lactam drugs:
- Vancomycin: 15 mg/kg/12h i.v (with determination of trough plasma levels on day 2-3 of treatment if available).
- Linezolid: 600 mg/12 hours (i.v)
- Daptomycin: 8-10 mg/kg/day (i.v).
Intra-abdominal or soft tissue infections meeting study criteria, for which a polymicrobial infection is suspected:
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 (18 years of age or older) hospitalised with monomicrobial E. faecalis or E. faecium bacteremia.
- •Negative follow-up blood cultures performed between days 2 and 3 of active treatment.
- •Disappearance of fever (>37.8ºC) within the first 72 hours.
- •Signed informed consent.
- •The previous version allowed this inclusion criterion "Early adequate control of the source of bacteremia within 72 hours in the cases in which it is feasible and necessary (urinary or biliary tract release; abscess drainage; catheter-removal, etc)", which is now removed because it is already an exclusion criterion.
排除标准
- •patients with polymicrobial bacteremia
- •Patients with limited life expectancy in whom only conservative clinical management had been decided.
- •Hemodynamic instability on day 5-6 after the start of active treatment.
- •Patients wearing endovascular devices or prosthetic heart valves.
- •Source of uncontrolled bacteremia adequately defined as undrained abscess, bile duct infection associated with plastic prostheses not removed or not replaced within the first 72 hours of bacteraemia, other infections related to non-removed prostheses, prostatitis, and infective endocarditis, as well as infections that require prolonged treatment, such as joint and bone infections.
- •Existence of a secondary focus, different from the initial one, or presence of metastatic focus of infection.
- •Severe neutropenia (<500 cells / mm3) at the time of bacteremia diagnosis.
- •Pregnancy and lactation.
研究组 & 干预措施
Short-treatment of any active antibiotic regimen
7 days from the initiation of an appropriate antimicrobial therapy and documented resolution of bacteremia (negative control blood cultures performed on day 2 or 3)
干预措施: Short-treatment of any active antibiotic regimen 7 days of any active antibiotic treatment for uncomplicated enterococcal bacteremia. (Drug)
Long-treatment of any active antibiotic regimen
14 days of any active antibiotic treatment from the date of the last positive blood culture and documented resolution of bacteremia (negative control blood cultures performed on day 2 or 3)
干预措施: Long-treatment of any active antibiotic regimen 14 days of any active antibiotic treatment for uncomplicated enterococcal bacteremia. (Drug)
结局指标
主要结局
Clinical success
时间窗: TOC (Test of cure) visit (performed at day 28-32 after the end of suitable antibiotic treatment) or if drainage occurs after day 7 of treatment, TOC is to be done 7 days after that day.
Clinical success , composite endpoint defined as all the following: (a) survival at TOC; (b) absence of enterococcal bacteremia relapse or infective endocarditis diagnosis at TOC; (c) no need to prolong therapy beyond the pre-established duration, or restart drugs against enterococci for any reason within 30 days.
次要结局
- Rates of relapse or infective endocarditis diagnosis(TOC visit (day 28-32 ) and follow-up visit at day 90)
- Number of participants with Adverse Events due to antibiotic treatment(From date of randomization until the last follow up visit planned 90 days of the initiation of antibiotic administration)
- Incidence of secondary infections(TOC visit (on day 28-32) and follow-up visit at day 90)
- Change in SOFA score (Sepsis related Organ Failure Assessment)(Visit 0 (baseline) and TOC visit (on day 28-32) and follow-up visit at day 90)
- Survival(TOC visit (day 28-32) and follow-up visit at day 90)
- Length of hospital stay(From patient first day inhospital (day of admission) until patient hospital discharge due to cure or home follow up assessed up to 30 days of the initiation of antibiotic administration)
- Duration of intravenous and total therapy(From date of randomization until the last follow up visit planned 30 days of the initiation of antibiotic administration)
- Incidence of diarrhoea by C. difficile(From date of randomization until the last follow up visit planned 30 days of the initiation of antibiotic administration)