Comparison of Short Infusion Versus Prolonged Infusion of Ceftolozane-tazobactam Among Patients With Ventilator Associated-pneumonia to Pseudomonas Aeruginosa in Intensive Care Units
试验速览
- 阶段
- 3 期
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Time that the concentration spends above 5 Minimum inhibitory Concentration (T>5*MIC)
研究概览
简要总结
The main objective of this study is to compare the median exposures at pharmacokinetic equilibrium of the two modalities of administration: 4-hours infusion of ceftolozane-tazobactam at a dosage of 2 gram three times a day vs 1-hour infusion of 2 gram three times a day.
详细描述
Intensive care unit patients with ventilator associated-pneumonia often develop severe and rapidly life threatening Gram-negative Bacillus infections. Moreover, they present pathophysiological disturbances responsible for major pharmacokinetic changes (volume of distribution and glomerular filtration) which may lead to drugs under-exposure. Any delay in management or inadequate antibiotic therapy can have serious consequences in terms of prognosis. The association ceftolozane-tazobactam is an alternative to carbapenems in documented infections. Ceftolozane is a new cephalosporin, marketed, in combination with tazobactam (beta-lactamase inhibitor) under the name ZERBAXA®. ZERBAXA® is active on Gram-negative Bacillus, including Pseudomonas aeruginosa.
This is a prospective, randomized, open pharmacokinetic/pharmacodynamic study that compares two modalities of administration of a novel antibiotic, ZERBAXA® ceftolozane-tazobactam, by 4-hours infusion at the dosage of 2 gram three times a day vs. 1-hour infusion at the dosage of 2 g three times a day, among patients with ventilator associated-pneumonia to Pseudomonas aeruginosa.
The patient will be randomized either in the 4-hours or in the 1-hour infusion group. Follow up visits are daily for any intensive care patient. Those provided for biomedical research are carried out during the treatment period, at Day 15 and Day 28. For the pharmacokinetic study, 7 blood samples will be collected from 24 hours to 48 hours after the first ZERBAXA® administration.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1 hour infusion
The first group corresponds to 1-hour infusion : First administration of ceftolozane-tazobactam with 2000 mg by infusion for 60 minutes every 8 hours.
24h after this first administration, 7 blood samples will be collected at Hour 24, Hour 25, Hour 26, Hour 28, Hour 30, Hour 32 and Hour 48.
干预措施: 1 hour infusion (Drug)
4 hours infusion
The second group corresponds to 4-hours infusion: First administration of ceftolozane-tazobactam with 2000 mg by infusion for 4 hours every 8 hours. 24h after this first administration, 7 blood samples will be collected at Hour 24, Hour 25, Hour 26, Hour 28, Hour 30, Hour 32 and Hour 48.
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干预措施: 4 hours infusion (Drug)
结局指标
主要结局
Time that the concentration spends above 5 Minimum inhibitory Concentration (T>5*MIC)
时间窗: Time between two administrations (8 hours)
The primary endpoint is the time that the concentration spends above 5\* Minimum inhibitory Concentration, expressed as a percentage of the time interval between two administrations. The T\>5\* Minimum inhibitory Concentration will be determined for each patient from the concentration profile measured over an 8-hour post-administration interval. Since protein binding is low (\<20%), the total concentration (sum of free form and plasma protein bound) will be used as a marker for free concentration. Therefore, the T\>5\* Minimum inhibitory Concentration will be calculated from the total concentrations. Our study will focus on only Pseudomonas aeruginosa Pneumonia acquired under mechanical ventilation with a critical Minimum inhibitory Concentration of 4 mg/l, T\>5\* Minimum inhibitory Concentration will then correspond to a residual serum concentration of 20 mg/l.
次要结局
- Bactericidal rate(at Day 10)
- Survival at D28(at Day 28)
- Percentage of patients with concentrations greater than 5*Minimum inhibitory Concentration(Time between two administrations (8 hours))
- Percentage of patients recovering at the end of the treatment period(at Day 10)
- Percentage of patients failing at the end of the treatment period(at Day 10)
- The duration of hospitalization(at Day 28)
- Number of days without artificial ventilation(at Day 28)
- The alveolar concentration of Ceftolozane-Tazobactam(between 24 hour and 48 hour after time 0)
- Evaluation of the serious adverse events(Day 28)