" Study of the Benefit of Nebulized Amikacin in the Treatment of Gram-negative Bacillus Pneumonia Acquired During Mechanical Ventilation in Patients Receiving Extracorporeal Membrane Veno-arterial Oxygenation "
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Bacterial eradication rate
研究概览
简要总结
Pneumonia are the most frequent infectious complication in patients on Extracorporeal Membrane Oxygenation Veno-arterial (ECMO-VA), with a treatment failure rate of around 40%, even though antibiotic therapy is tailored to the germs identified. One hypothesis to explain this particularly high failure rate is the reduced pulmonary blood flow associated with ECMO offloading of the heart. Although there are no data to date on the pulmonary penetration of antibiotics in patients undergoing VA-ECMO, this phenomenon of pulmonary hypoperfusion could contribute to altering the alveolocapillary diffusion of antibiotics, thereby reducing their concentration in the pulmonary parenchyma.
Our hypothesis is that amikacin nebulization could increase bacterial clearance and, ultimately, limit treatment failure or recurrence of gram-negative bacilli (GNB) pneumonia in patients undergoing VA-ECMO.
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
- •Patient 18 years or older
- •Circulatory assistance by veno-arterial ECMO for at least 24 hours prior to documentation of pneumonia
- •Invasive mechanical ventilation
- •Diagnostic suspicion of pneumonia based on evocative criteria (presence of at least 2 of the following criteria): fever (superior to
- •5°C), hypothermia (inferior to 36.0°C), hyperleukocytosis (superior to 11 × 10^9 l-1) or leukopenia (inferior to 4 × 10^9 l-1), purulent tracheobronchial secretions, altered oxygenation with need to increase FiO2 on ECMO or ventilator for the same SaO2 or PaO2 target, new or persistent pulmonary infiltrate(s) on chest x-ray in bed, or image suggestive of pneumonia on chest CT, or consolidation of appearance suggestive of an infectious origin on pulmonary ultrasound.
- •And microbiological confirmation of Gram-negative ventilator-associated pneumonia by quantitative culture on bronchoalveolar lavage (BAL, significance threshold superior to 10^4 CFU/ml) or protected distal sampling (PDP, significance threshold superior to 10^3 CFU/ml).
- •Probabilistic antibiotic therapy with piperacillin - tazobactam
- •Informed consent obtained from the patient or trusted support person if unable to consent at the time of inclusion, or inclusion procedure in emergency situations.
- •Patient affiliated to social security (excluding AME)
排除标准
- •Known allergy to amikacin or another aminoglycoside or to an auxiliary drug or to any of their excipients.
- •Contraindication to the administration of amikacin or its excipients listed in the summary of product characteristics.
- •Contraindication to the administration of an auxiliary drug or to one of its excipients listed in the summary of product characteristics.
- •Contraindications to nebulization
- •Intravenous antibiotic therapy started more than 72 hours before randomization
- •Probabilistic venous antibiotic therapy other than piperacillin - tazobactam
- •Administration of inhaled antibiotics within 7 days prior to inclusion
- •Positive pregnancy test for women of childbearing potential
- •Presence of HIV infection with CD4 count inferior to 200 cells/mm3 or fungal lung infection or pulmonary abscess or empyema
- •Presence of renal insufficiency with creatinine clearance inferior to 15 ml/min, with the exception of patients receiving continuous renal purification or daily hemodialysis sessions as part of their intensive care unit management.
- •Patent moribund (SAPS II superior to 75) or high probability of death within 48 hours
- •Patient under legal protection (curatorship, guardianship or safeguard of justice)
- •Participating in another interventional clinical trial or within the exclusion period at the end of a previous study.
研究组 & 干预措施
Standard of care
干预措施: Standard of care (Drug)
Amikacine nebulization associated with Standard of care
干预措施: Amikacin (Drug)
结局指标
主要结局
Bacterial eradication rate
时间窗: Day 5
Bacterial eradication rate, defined as absence of germs on direct examination and negative culture of a tracheal aspirate taken on day 5 (D5) after randomization and at least 12 hours after the last administration of inhaled amikacin.
次要结局
- Clinical cure rate(Day 5)
- Pneumonia persistence rate(Day 5)
- Change in clinical pulmonary infection score (CPIS)(Day 0 to Day 5)
- Change in pulmonary aeration score(Day 0 to Day 5)
- Adverse events(Day 0 to Day 5)
- Pharmacokinetic analysis of piperacillin tazobactam(Day 1)
- Alveolar fluid penetration ratio of piperacillin-tazobactam(Day 1)
- Pharmacokinetic analysis of Amikacin(Day 1 to Day 5)
- Alveolar fluid concentration of Amikacin(Day 1)