Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia: a Randomized Controlled Double-blind Study From the Skip-icu Consortium
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 181
- 试验地点
- 1
- 主要终点
- Rate of endotracheal intubation
研究概览
简要总结
The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 1%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management.
In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults patients aged 80 years or less
- •COVID-19 diagnosis defined as either positive RT-PCR for SARS-CoV-2 or COVID-19 compatible or typical chest CT pattern or positive serology for COVID-19 antibodies
- •Hypoxemic acute respiratory failure with the following criteria: oxygen saturation level of 92% or less, as measured by pulsed oximetry (SpO2) under oxygen therapy with an oxygen rate of 6L/min or more.
- •Hospital admission for COVID-19 within 14 days
- •Patients affiliated
排除标准
- •Hypersensitivity to the active substance or to any of the excipients
- •Pregnancy or breastfeeding woman
- •Known Hepatic failure (PT <50%, Factor V < 50%)
- •Last known Plasma total bilirubin > 21 μmol/L
- •Lactate level > 4 mmol/L
- •ALT and AST levels greater than 3 times the upper limit
- •Pulmonary hypertension (PAPs ≥37 mmHG and/or VmaxIT ≥ 2,9 m/s) or right ventricular dysfunction
- •History of pulmonary embolism
- •Diagnosis of pulmonary embolism during the current hospitalization or on-going anticoagulant therapy at curative dose for thromboembolism when hospitalized
- •PaCO2 > 45 mmHg
- •Exacerbation of asthma or chronic respiratory failure
- •Cardiogenic pulmonary oedema
- •Systolic blood pressure of 90 mmHg or less, or use of vasopressors
- •Urgent need for endotracheal intubation at the discretion of the treating physician
- •Do-not-intubate order or estimated life expectancy less than 6 months
- •Participation in another interventional research
研究组 & 干预措施
Almitrine
干预措施: Almitrine (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Rate of endotracheal intubation
时间窗: 7 days
Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
次要结局
- Number of ventilator-free days(28 days)
- 28-day mortality(28 days)
- In-hospital mortality(28-day)
- Number of days in the hospital(28 days)
- Discontinuation rate of the treatment(28 days)
- Number of days in the ICU(28 days)