Efficacy and Toxicity of Aerosolised Colistin in Ventilator Associated Pneumonia: A Prospective, Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 133
- 试验地点
- 1
- 主要终点
- cure of VAP
研究概览
简要总结
the management of Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) gram-negative bacilli (GNB) represent a real therapeutic dilemma in intensive care unit (ICU). Colistin remains an effective agent against MDR GNB. However, because of its side effects, mainly nephrotoxicity, other modalities than the intra venous (IV) route should be tried. Several recent data emphasize the interest of inhaled route. The investigators purpose was to evaluate the effectiveness and systemic toxicity of aerosolized colistin in ventilator associated pneumonia.
详细描述
prospective, randomized, single-blind study comparing two groups of patients treated with aerosolised (AS) colistin versus colistin intravenously (IV). Included were patients who have mechanical ventilation over 48 hours and that have developed a VAP. A VAP was defined as a CPIS (Clinical Pulmonary Infection Score) >6. Exclusion criteria were septic shock and/or bacteraemia. Included patients were divided into two randomized groups. The 1st received colistin in AS as 4 MU by nebulisation 3 times per 24 h. The 2nd received colistin in IV as a loading dose of 9 MU followed by 4.5MU two times per 24 h. Colistin was given for 14 days or until extubation. Patients were followed for 28 days. Therapeutic efficacy was assessed by a primary outcome: the cure of VAP at day 14 of therapy and defined as resolution of clinical and biological signs of infection that means a CPIS< 6 and bacteriological eradication. Secondary outcomes: duration of mechanical ventilation, ICU stay-length and mortality at day 28. Systemic toxicity was assessed by the occurrence of acute renal failure (ARF) defined as increase of plasma creatinine more than 1.5 times its base value.
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
- Single (Participant)
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
- •Critically ill patients older than 18 years, with mechanical ventilation during more than 48 hours, and who have presented a Ventilator associated Pneumonia (VAP) defined as a CPIS (Clinical Pulmonary Infection Score) of more than six
排除标准
- •Age <18 years
- •Pregnancy
- •Septic shock
研究组 & 干预措施
aerosolised (AS) colistin group
the intervention was: AS colistin and "imipenem. the drug administered was colimycin (colistin) powder 1 million units (MU) by a flakon (Sanofi Winthrop Industry) at the dosage of 4 million units (MU) for 30 minutes 3 times per day for at least 14 days in addition to IV imipenem 1 g three times per day. Nebulisation was made via an ultrasonic vibrating plates nebulizer (Aeroneb Pro® Aerogen Nektar Corporation, Galway, Ireland). Inhaled colimycin® requires specific settings of the ventilator to limit turbulence inspiratory flow. The adjustment consisted in a volume controlled mode with a Tidal volume <8 ml / kg, respiratory rate at 12 cycles / min, I / E: 1/1 and an end inspiratory break > 20%.
干预措施: AS colistin and "imipenem" (Drug)
aerosolised (AS) colistin group
the intervention was: AS colistin and "imipenem. the drug administered was colimycin (colistin) powder 1 million units (MU) by a flakon (Sanofi Winthrop Industry) at the dosage of 4 million units (MU) for 30 minutes 3 times per day for at least 14 days in addition to IV imipenem 1 g three times per day. Nebulisation was made via an ultrasonic vibrating plates nebulizer (Aeroneb Pro® Aerogen Nektar Corporation, Galway, Ireland). Inhaled colimycin® requires specific settings of the ventilator to limit turbulence inspiratory flow. The adjustment consisted in a volume controlled mode with a Tidal volume <8 ml / kg, respiratory rate at 12 cycles / min, I / E: 1/1 and an end inspiratory break > 20%.
干预措施: AS colimycin (colistin) (Drug)
aerosolised (AS) colistin group
the intervention was: AS colistin and "imipenem. the drug administered was colimycin (colistin) powder 1 million units (MU) by a flakon (Sanofi Winthrop Industry) at the dosage of 4 million units (MU) for 30 minutes 3 times per day for at least 14 days in addition to IV imipenem 1 g three times per day. Nebulisation was made via an ultrasonic vibrating plates nebulizer (Aeroneb Pro® Aerogen Nektar Corporation, Galway, Ireland). Inhaled colimycin® requires specific settings of the ventilator to limit turbulence inspiratory flow. The adjustment consisted in a volume controlled mode with a Tidal volume <8 ml / kg, respiratory rate at 12 cycles / min, I / E: 1/1 and an end inspiratory break > 20%.
干预措施: AS colistin and imipenem (Drug)
intravenous (IV) colistin goup
the intervention was: IV colistin and "imipenem. the intravenous (IV) colistin goup received IV colimycin (colistin) as a loading dose of 9 MU during 60 minutes followed by 4.5 million units 2 times per day in addition to IV imipenem 1 g three times per day.
干预措施: IV colistin " and "imipenem" . (Drug)
intravenous (IV) colistin goup
the intervention was: IV colistin and "imipenem. the intravenous (IV) colistin goup received IV colimycin (colistin) as a loading dose of 9 MU during 60 minutes followed by 4.5 million units 2 times per day in addition to IV imipenem 1 g three times per day.
干预措施: IV colimycin (colistin) (Drug)
intravenous (IV) colistin goup
the intervention was: IV colistin and "imipenem. the intravenous (IV) colistin goup received IV colimycin (colistin) as a loading dose of 9 MU during 60 minutes followed by 4.5 million units 2 times per day in addition to IV imipenem 1 g three times per day.
干预措施: IV colistin and imipenem (Drug)
结局指标
主要结局
cure of VAP
时间窗: day 14 of therapy
a CPIS (clinical pulmonary infection score) less than 6 and bacterial eradication
次要结局
- occurrence of acute renal failure(From date of randomization until the time of the cessation of colistin, assessed up 14 days on average)
- duration of mechanical ventilation(From date of randomization until the time of weaning from ventilator, an average of 14 days)
- length of stay in intensive unit(from randomisation until the time of patient discharge, an average of 28 days)
研究者
Ahlem Trifi
doctor
Tunis University