Continuous Infusion Versus Intermittent Administration of Meropenem in Critically Ill Patients: A Multicenter Randomized Double Blind Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 607
- 试验地点
- 26
- 主要终点
- Death or Emergence of new resistant bacteria
研究概览
简要总结
This study arises from the need to optimize antibacterial drug usage to face increasing drug resistance among gram-negative pathogens in intensive care units. Gram-negative organisms are responsible for 70% of drug-resistant infections acquired in the intensive care unit. Meropenem is a β-lactam, carbapenem, antibacterial agent usually administered by intermittent infusion. As β-lactam efficacy is determined by the time in which the drug concentration exceeds the minimum inhibiting concentration of the target pathogen, intermittent infusion of this short half-lived drug can lead to precipitous drops in serum drug levels, an occurrence linked to emergence of resistant pathogens. The investigators hypothesize a beneficial effect of a continuous meropenem infusion on mortality and emergence of drug resistant pathogens. All patients enrolled will receive 1 g of meropenem bolus. After that, subjects will be randomized to receive a continuous infusion of study drug 3g/day or a bolus administration of the same amount of drugs. The investigators expect a reduction of mortality and emergence of extensive or pan drug resistant pathogens from 52 to 40% in the continuous infusion group.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Will be enrolled patients who:
- •Are able to express informed consent or the latter can be given by his/her next of kin or as requested by Ethical Committee.
- •Need a new antibiotic treatment, by clinical judgment, with meropenem
- •Are admitted to ICU
- •Have Sepsis or septic shock. Sepsis defined as having all the following
- •SIRS (Systemic Inflammatory Response Syndrome);
- •suspected or documented infection;
- •a SOFA score ≥
- •Septic shock defined as having all the following 1.Sepsis;
- •Persisting hypotension requiring vasopressors to maintain MAP ≥65mmHg and having a serum lactate level >2 mmol/L (18mg/dL) despite adequate volume resuscitation.
排除标准
- •Will be excluded patients who:
- •Are able to express informed consent and deny it
- •Are already receiving study drug or other carbapenem both as a bolus or continuous infusion
- •Have a known allergy or intolerance to study drug, to other carbapenem antibacterial agents or severe allergic reaction to β-lactam antibacterial agents or to anhydrous sodium carbonate (study drug excipient)
- •Have a little chance of survival, as defined by a SAPS II score greater than 65
- •Have concomitant acquired immunodeficiency syndrome (stage 3 according to CDC)
- •Received immunosuppressant or long-term corticosteroid therapy (more than 0.5 mg/kg/day for over 30 days)
研究组 & 干预措施
Continuous infusion
Patient randomized to continuous infusion group, will receive a continuous infusion of meropenem according to their renal function (creatinine clearance -ClCr- estimated by Cockcroft-Gault formula and study day
- for ClCr > 50 ml/min: 3 g / day, prepared as follows: 10 mg/ml of meropenem in NaCl 0.9% at 12,5 ml/h.
- for ClCr < 50 ml/min: 2 g / day, prepared as follows: 10 mg/ml of meropenem in NaCl 0.9% at 8,3 ml/h.
This solution will be replaced every time its duration exceeds the stability in use stated by the producer
干预措施: Meropenem (Drug)
Bolus
Patient randomized to bolus group, will receive a bolus infusion of meropenem according to their renal function (creatinine clearance -ClCr- estimated by Cockcroft-Gault formula):
- for Cl-Cr > 50 ml/min 1 g every 6 hours on first 24 hours, every 8 hours after
- for Cl-Cr < 50 ml/min 1 g every 8 hours on first 24 hours, every 12 hours after
干预措施: Meropenem (Drug)
结局指标
主要结局
Death or Emergence of new resistant bacteria
时间窗: day 28
composite outcome: 1. death from any cause at day 28 2. emergence of new XDR (extended drug resistant) or PDR (pan drug resistant) bacteria at day 28
次要结局
- Death from any cause(day 90)
- Antibiotic-free days(up to day 28 or death)
- ICU - free days(day 28 or death)
- Cumulative SOFA-free point(up to day 28)
研究者
Giovanni Landoni
MD, Full Professor
Università Vita-Salute San Raffaele