Open Label Randomized Controlled Trial of Ultraprotective Ventilation Without Extracorporeal Circulation in Patients With COVID 19 Pneumonia and Moderate to Severe ARDS
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 220
- 试验地点
- 22
- 主要终点
- A composite score based on all-cause mortality and the number of ventilator free-days (VFD)
研究概览
简要总结
Mortality of COVID-19 pneumonia with acute respiratory distress syndrome (ARDS) is extremely high in preliminary reports amounting to 50-60%. Duration of mechanical ventilation in these patients appears to exceed standard duration of mechanical ventilation in non-COVID-19 ARDS patients, suggesting that COVID-19 patients may be particularly at risk for ventilator-induced lung injury. Treatment of COVID-19 ARDS patients is to date mainly supportive with protective mechanical ventilation (ventilation with low tidal volume (VT) i.e. 6 ml/kg of predicted body weight (PBW) and plateau pressure control below 30 cm H2O).
Mechanical ventilation with VT reduction below 6 ml/kg PBW in ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury. Investigators recently performed a multicenter pilot study on 34 moderately severe to severe ARDS patients. This study demonstrated that ultraprotective ventilation with ultra-low VT (≤4.2 ml/kg PBW) without extracorporeal circulation may be applied in approximately 2/3 of the patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients. Investigators hypothesized that ultraprotective ventilation without extracorporeal circulation may reduce the mortality at day-90 and increase the number of days free from mechanical ventilation (VFD) at day-60, as compared to protective ventilation.
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
- •Adults aged 18 years or older
- •ARDS according to the Berlin definition
- •COVID-19 pneumonia confirmed by RT-PCR
- •Acute respiratory failure not fully explained by left ventricular failure or sodium overload
- •Bilateral pulmonary radiological opacities not fully explained by pleural effusions or atelectasis or nodules
- •Invasive mechanical ventilation with PaO2/FiO2 ≤ 150 mm Hg and PEEP ≥ 5 cm H2O with a tidal volume below or equal to 6 ml per kilogram of predicted body weight
- •Continuous intravenous sedation as part of ARDS treatment
排除标准
- •Exclusion criteria related to ARDS history
- •ARDS onset more than 48 hours before inclusion
- •previous inclusion in present study
- •Exclusion criteria related to ARDS severity or complications
- •arterial pH < 7.21 despite respiratory rate set to 35/min at the time of inclusion
- •patient under any extracorporeal CO2 removal technique or ECMO
- •pneumothorax or bronchopleural fistula
- •Exclusion criteria related to comorbidities
- •suspected intracranial hypertension
- •severe chronic obstructive pulmonary disease defined by a GOLD score ≥ 3
- •chronic respiratory failure under home oxygen or non-invasive ventilation
- •chronic respiratory failure requiring long term oxygen or non-invasive ventilation
- •obesity with body weight over height ratio greater than 1 kg/cm
- •sickle cell disease
- •bone marrow transplant < 6 months
- •burn injury with extension greater than 30% of body surface area
- •cirrhosis with Child-Pugh score C
- •advance directives to withhold or withdraw life sustaining treatment
- •Exclusion criteria related to legislation
- •Patient under an exclusion period relative to participation to another clinical trial, or inclusion into a clinical trial interfering with the ventilatory strategies
- •pregnancy, lactating women
- •patient under a legal protective measure.
- •lack of affiliation to social security as required by French regulation
- •lack of written informed consent by patient or next of kin (unless if recourse to the emergency procedure in the absence of a loved one)
结局指标
主要结局
A composite score based on all-cause mortality and the number of ventilator free-days (VFD)
时间窗: Day 90
For an alive patient at day 90, the score will be built as follow: a value +1 will be given for comparisons to dead patients and alive patients with a lower number of VFD. For comparisons to alive patients with a higher number of VFD a value -1 will be given and in case of identical number of VFD a value 0 will be given. For a dead patient a value -1 will be given for comparisons to alive patients and 0 for comparisons to dead patients. For a given patients the score will correspond to the sum of values resulting to the comparison to all patients of the other group. A higher score indicates a more favorable result.
次要结局
- Length of hospital stay(90 days)
- All-cause mortality (intention to treat)(90-day after inclusion)
- Daily sedation dose during the first 14 days of the study(14 days)
- Incidence density rate of any serious adverse events(ICU stay)
- Quality of life assessed by the RAND 36-Item Health Survey (SF-36) score(Day 365 after inclusion)
- Time to successful extubation(60 days)
- Respiratory parameters assessed daily from inclusion to weaning of deep sedation or 14 days whichever comes first(14 days)
- Incidence density rate of acute cor pulmonale(ICU stay)
- Incidence density rate of barotrauma(ICU stay)
- Cost-efficacy ratio of the innovative strategy compared to the reference strategy(Day 90 after inclusion)
- Post-traumatic stress disorder assessed by the Impact of Event Scale - revised (IES-R) score by phone call(Day 365 after inclusion)
- Ventilator-free days (VFD)(day 60 after inclusion)
- All-cause mortality with per protocol analysis(90-day)
- Rate of use of rescue therapies(14 days)
- Incidence density rate of severe mixed acidosis(ICU stay)
- Incidence density rate of ventilator associated pneumonia(ICU stay)
- Cognitive impairment assessed by phone call using the Telephone Montreal Cognitive Assessment (T-MoCA) test(Day 365 after inclusion)