Randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of intravenous metoprolol in patients with Acute Respiratory Distress Syndrome (ARDS).
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Not specified
- Sponsor
- Consorcio Centro De Investigacion Biomedica En Red
- Enrollment
- 350
- Locations
- 8
- Primary Endpoint
- 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)
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
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)
Detailed Description
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.
Investigators
Projects Department (CIBER)
Scientific
Consorcio Centro De Investigacion Biomedica En Red
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •Prolonged hospital admission prior to randomisation (i.e. ≥7 days at the time of randomisation).
- •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).
- •Reduced left ventricular ejection fraction (LVEF <50%).
- •Life expectancy due to other processes (cancer, degenerative diseases, etc.) of les tan 6 months.
- •Right ventricular (RV) systolic dysfunction.
Outcomes
Primary Outcomes
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)
Secondary Outcomes
- 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