Randomised Controlled Trial of Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Due to Enterobacteriaceae Showing Resistance to Third Generation Cephalosporins
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 334
- 试验地点
- 29
- 主要终点
- Number of participants with a "success" at the test of cure (TOC)
研究概览
简要总结
A Phase 3, Multicenter, Randomised, Controlled, Open-Label Study to demonstrate noninferiority of temocillin (unauthorized investigational medicinal product IMP in Spain, but authorized in Belgium and UK) vs a carbapenem antibiotic (meropenem) in adults with bacteraemia due to third-generation cephalosporin-resistant Enterobacteriaceae.
The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous treatment, the sequential oral treatment is permitted if the patient meets appropriate conditions.
详细描述
The objective of the trial is to demonstrate the non-inferiority of temocillin (2g each 8 hours, intravenous) to carbapenems (meropenem 1g each 8 hours, intravenous) in terms of efficacy and safety in the targeted treatment of bacteraemia due to Enterobacteriaceae resistant to third-generation cephalosporins, and therefore provide evidence for the use of temocillin in these infections.
The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous treatment, the sequential oral treatment is permitted if the patient meets appropriate conditions.
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 with monomicrobial bacteremia due to Enterobacteriaceae showing resistance to cefotaxime, ceftriaxone (MIC >2 mg/L) and/or ceftazidime (MIC >4 mg/L), and sensible to temocillin (MIC ≤8 mg/L, except in bacteremia only of urinary origin, for which the criterion is MIC ≤16 mg/L ) and meropenem (MIC ≤2 mg/L).
- •Patients with polymicrobial bacteremia caused by more than one Enterobacteriaceae species may also be included, provided at least one of them is resistant to third-generation cephalosporins, and both are susceptible to meropenem and temocillin.
- •Duration of intravenous treatment is planned to be at least 4 days from randomization, or 3 days if the empirical treatment prior to randomization was active.
- •The patient signed informed consent form.
- •Potentially fertile patients must have a negative pregnancy test.
排除标准
- •<18 years
- •Pregnancy
- •Breastfeeding
- •Terminal condition, with life expectancy of less than 30 days, or palliative care , such that no actions will be taken to control the source of infection if necessary. Patients receiving palliative care with a life expectancy greater than 30 days may be included if source control is not necessary or, if necessary, will be carried out.
- •Allergy to betalactams
- •Polymicrobial bacteraemia (except when the other microorganism is considered a contaminant, (e.g. coagulase-negative staphylococci or diphtheroids in a single blood culture, or in cases where more than one Enterobacteriaceae species is isolated, provided that at least one isolate is resistant to third-generation cephalosporins and both are susceptible to meropenem and temocillin).
- •Infections typically needing prolonged >14 days of therapy (e.g., endocarditis, prosthetic joint infection, vascular graft infection, empyema, chronic prostatitis) or meningitis. Patients who initially do not have a confirmed diagnosis of these infections may be included; if the diagnosis is made subsequently, the patient may be kept in the trial at the discretion of the investigator, establishing the duration of treatment that he considers necessary.
- •Active empirical treatment> 96 hours after initial blood culture extraction
- •Delay in inclusion> 48 h
- •Recruited in another clinical trial with active treatment
- •Peritoneal dialysis or continuous hemofiltration
研究组 & 干预措施
Temocillin
Patients enrolled in this arm, will receive 2g each 8 hours of intravenous temocillin.
干预措施: Temocillin (Drug)
Meropenem
Patients enrolled in this arm, will receive 1g each 8 hours of intravenous meropenem.
干预措施: Meropenem (Drug)
结局指标
主要结局
Number of participants with a "success" at the test of cure (TOC)
时间窗: Up to 7-10 days after the last day of antibiotic therapy
A success at the test of cure is the resolution of infection symptoms
Survival at day 28
时间窗: At day 28.
Number of patients who are alive
Number of patients who do not need to prolong therapy beyond 14 days
时间窗: Up to 7-14 days after the last day of antibiotic therapy
Assigned treatment to be administered for less than 14 days
Not recurrence until day 28
时间窗: At day 28.
Recurrence is reappearance of symptoms with positive blood culture for the same microorganism. Participants with recurrence will not meet the primary outcome.
Number of patients who do not need to stop or change the assigned drug
时间窗: Up to 7-14 days after the last day of antibiotic therapy
Reasons for not change can be no adverse event, no perceived failure during treatment or no occurrence of a superimposed infection. Participants who stop or change the assigned drug will not meet the primary outcome.
次要结局
- Length of hospital stay (days)(Through study completion, an average of 28 days)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(Up to day 28)
- Length of intravenous therapy (days)(From day 1 of intravenous antibiotic treatment administration to last intravenous administration, average 14 days)
- Changes in Sequential Organ failure (SOFA) score(At days 1, 3, end of treatment (days 7-14) and visit 4)
- Changes in Barthel Index for Activities of Daily Living (ADL) for patients older than 70 years old(At days 1, 3, end of treatment (days 7-14) and visit 4)
- 28-day mortality(Up to day 28.)
- Length of total administration of therapy (days)(From day 1 of intravenous or oral antibiotic treatment administration to last intravenous or oral administration, average 14 days)
- Number of subjects with resistance development during therapy(Up to day 28)
- Recurrence rate(Up to day 28.)
- Number of subjects with development of superimposed infections.(Up to day 28.)