Randomised, Double-blind, Placebo-controlled Clinical Trial to Evaluate the to Assess the Efficacy of Intravenous Metoprolol in Patients With Acute Respiratory Distress Syndrome (ARDS).
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 20
- 主要终点
- Days alive and free of invasive mechanical ventilation during the first 28 days. [ Time Frame: 28 days ] Hierarchical composite outcome "Alive and ventilator-free days at 28 days" (win ratio approach)
研究概览
简要总结
Randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy of intravenous metoprolol in patients with Acute Respiratory Respiratory Distress Syndrome (ARDS).
详细描述
This is a placebo-controlled, randomised, double-blind, multicentre, Phase III clinical trial to assess the efficacy of IV metoprolol in newly intubated ARDS patients, assessing survival and days free of invasive mechanical ventilation during the first 28 days. Eligible participants shall have had orotracheal intubation (OTI) and mechanical ventilation within 72 hours prior to randomisation, moderate-severe ARDS (PaO2/FiO2: ≤200 mmHg under standardised conditions (PEEP≥5 cm H2O), a heart rate ≥ 60 bpm and invasive systolic blood pressure ≥ 110 mmHg.The trial will include a total of n=350 patients, with two treatment arms: metoprolol vs. placebo (1:1). Each of the 7 days of treatment, participants will be receive 15 mg of iv metoprolol tartrate or matching placebo in 100 ml of saline for 10 minutes.
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)
盲法说明
Both metoprolol and saline are supplied in 5 ml ampoules of the same shape, structure and colour
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
- •Patients (≥18 years and <80 years) with a clinical diagnosis of ARDS of any aetiology (pneumonia, including SARS-CoV-2, sepsis, pancreatitis, bronchospasm and trauma) admitted to the ICU.
- •Orotracheal intubation (OTI) and mechanical ventilation within 72 hours prior to randomisation.
- •Moderate-severe ARDS (PaO2/FiO2: ≤200 mmHg under standardised conditions (PEEP≥5 cm H2O).
- •Heart rate ≥ 60 bpm.
- •Invasive systolic blood pressure ≥ 110 mmHg.
排除标准
- •Prolonged hospital admission prior to randomisation (i.e. ≥7 days at the time of randomisation).
- •Reduced left ventricular ejection fraction (LVEF <50%).
- •Life expectancy due to other processes (cancer, degenerative diseases, etc.) of less than 6 months.
- •Right ventricular (RV) systolic dysfunction.
- •Concomitant acute heart failure (cardiac index ≤2.5 L/m2 or pulmonary capillary pressure ≥15 mmHg or clinical suspicion).
- •Second-degree atrioventricular (AV) block, 2:1 AV block, high-grade/advanced AV block and third-degree AV block. Also significant sinus bradycardia, which would be implied by having a heart rate >60 bpm as an inclusion criterion.
- •Pregnant or breastfeeding women.
- •Cardiogenic shock.
- •Persistent invasive blood pressure <110 mmHg despite vasopressor agents.
- •Use of noradrenaline at concentrations greater than 0.2 µg/kg/min at the time of the randomisation.
- •Use of dobutamine within 48 hours before randomisation.
- •Concomitant pulmonary embolism.
- •Known severe peripheral arterial disease.
- •Known asthma before admission (with active bronchodilator therapy).
- •Active beta-blocker treatment prior to admission (i.e. within 3 months prior to admission).
结局指标
主要结局
Days alive and free of invasive mechanical ventilation during the first 28 days. [ Time Frame: 28 days ] Hierarchical composite outcome "Alive and ventilator-free days at 28 days" (win ratio approach)
Days alive and free of invasive mechanical ventilation during the first 28 days. [ Time Frame: 28 days ] Hierarchical composite outcome "Alive and ventilator-free days at 28 days" (win ratio approach)
次要结局
- Ventilator-free days at 28 days [ Time Frame: 28 days ] number of days without mechanical ventilation during the firs 28 days
- Intensive care unit days of admission [ Time Frame: 3 months ] Number of days admitted at the intensive care unit
- All-cause death at day 28 after randomization [ Time Frame: 28 days ] cumulative incidence of death from any cause
- Quality of life score [ Time Frame: at 3 months ] Mean quality of life score according to ''The Short Form 36 Health Survey Questionnaire'' (SF-36). The SF-36 is a 36 item scale, which measures eight domains of health status: physical functioning (10 items); physical role limitations (four items); bodily pain (two items); general health perceptions (five items); energy/vitality (four items); social functioning (two items); emotional role limitations (three items) and mental health (five ítems).
- Arterial oxygenation [ Time Frame: on day 8 ] Mean arterial oxygen saturation (PaO2/FiO2)
- Change in arterial oxygenation [ Time Frame: 8 days ] Mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8
研究者
Projects Department (CIBER)
Scientific
Consorcio Centro De Investigacion Biomedica En Red