Driving Pressure-guided Tidal Volume Ventilation in the Acute Respiratory Distress Syndrome: a Prospective, Multicenter, Randomized, Controlled, Open-label, Phase III Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 750
- 主要终点
- Mortality
研究概览
简要总结
Acute respiratory distress syndrome (ARDS) is associated with high mortality, some of which can be attributed to ventilator-induced lung injury (VILI) when artificial ventilation is not customized to the severity of lung injury. As ARDS is characterized by a decrease in aerated lung volume, reducing tidal volume (VT) from 12 to 6 mL/kg of predicted body weight (PBW) was shown to improve survival more than 20 years ago. Since then, the VT has been normalized to the PBW, meaning to the theoretical lung size (before the disease), rather than tailored to the severity of lung injury, i.e., to the size of aerated lung volume. During ARDS, the aerated lung volume is correlated to the respiratory system compliance (Crs). The driving pressure (ΔP), defined as the difference between the plateau pressure and the positive end expiratory pressure, represents the ratio between the VT and the Crs. Therefore, the ΔP normalizes the VT to a surrogate of the aerated lung available for ventilation of the diseased lung, rather than to the theoretical lung size of the healthy lung, and thus represents more accurately the actual strain applied to the lungs. In a post hoc analysis of 9 randomized controlled trials, Amato et al. found that higher ΔP was a better predictor of mortality than higher VT, with an increased risk of death when the ΔP > 14 cm H2O. These findings have been confirmed in subsequent meta-analysis and large-scale observational data. In a prospective study including 50 patients, the investigators showed that a ΔPguided ventilation strategy targeting a ΔP between 12 and 14 cm H2O significantly reduced the mechanical power, a surrogate for the risk of VILI, compared to a conventional PBW-guided ventilation. In the present study, the investigators hypothesize that the physiological individualization of ventilation (ΔP-guided VT) may improve the outcome of patients with ARDS compared to traditional anthropometrical adjustment (PBW-guided VT)
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
- •Age > 18 years
- •Invasive mechanical ventilation
- •Criteria for ARDS according to Berlin definition:
- •Bilateral infiltrates not fully explained by effusions, lobar/lung collapse, or nodules;
- •PaO2/FiO2 of 300 or less measured with a PEEP of at least 5 cm H2O
- •Respiratory failure not fully explained by cardiac failure or fluid overload These criteria must be observed for less than 72h
- •Affiliation to the social security system
- •Written consent obtained from the patients (from a support person, family member or a close relative if the patient is not able to expressing and sign consent) or inclusion without initial consent in case of emergency, if the patient is not able to express his/her consent and in the absence of support person, family member or a close relative
排除标准
- •Known pregnancy
- •Lung transplantation
- •Evident significant decrease in chest wall compliance (e.g., abdominal compartment syndrome)
- •Moribund patient not expected to survive 24 hours
- •Presence of an advanced directive to withhold life-sustaining treatment or decision to withhold life-sustaining treatment
- •Chronic respiratory disease requiring home oxygen therapy or ventilation
- •ECMO before inclusion
- •Pneumothorax
- •Enrollment in an interventional ARDS trial with direct impact on VT
- •Subject deprived of freedom, subject under a legal protective measure (guardianship/curatorship)
结局指标
主要结局
Mortality
时间窗: 28 days
The primary endpoint is a ranked composite score that prioritizes 28-day mortality, followed by days free from mechanical ventilation through day 28 for the survivors. Thus, the score is calculated in such a manner that death constitutes a worse outcome than fewer days off the ventilator.
Number of days free from mechanical ventilation
时间窗: 28 days
The primary endpoint is a ranked composite score that prioritizes 28-day mortality, followed by days free from mechanical ventilation through day 28 for the survivors. Thus, the score is calculated in such a manner that death constitutes a worse outcome than fewer days off the ventilator.
次要结局
- Arterial blood gases(up to Day 7)
- Mortality(Day-28, Day 90)
- Sequential Organ Failure Assessment score (SOFA)(Day 1, Day 3 and Day 7)
- Ventilator parameters(up to Day 7)
- Number of days alive without catecholamine(Up to Day 28)
- Number of days alive without ventilation(Up to Day 28)
- Number of days alive without continuous sedation(Up to Day 28)
- Number of days alive without neuromuscular blockers(UP to Day 28)
- Number of prone position sessions(Up to Day 28)
- Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R(Up to Day 28)
- Occurrence of ventilator-associated pneumothorax(Up to Day 28)
- Time to pressure support ventilation;(Up to Day 28)
- Total duration of mechanical ventilation(up to Day 7)
- Length of stay(up to Day 28)
- Duration of weaning unreadiness(Up to Day 28)
- Duration of weaning(Up to day 28)
- The rate of tracheostomy(Up to Day 28)