Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)
- Conditions
- Acute Respiratory Distress Syndrome (ARDS)
- Interventions
- Drug: saline 0.9%
- Registration Number
- 2024-515813-17-00
- 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.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 350
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.
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.
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 inclusión criterion.
Pregnant or breastfeeding women.
Cardiogenic shock.
Persistent invasive blood pressure <110 mmHg despite vasopresor agents.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Metoprolol Metoprolol Injection Participants will be administered IV Metoprolol tartrate 15 mg (3 ampoules of 5 ml) diluted in 100 ml of saline. Saline saline 0.9% Participants will be administered IV saline (0.9% sodium chloride) (3 ampoules of 5 ml) diluted in 100 ml of saline.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Ventilator-free days at 28 days [ Time Frame: 28 days ] number of days without mechanical ventilation during the firs 28 days 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 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 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). 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) 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 Change in arterial oxygenation [ Time Frame: 8 days ] Mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8
Trial Locations
- Locations (8)
Hospital Universitario De La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Jerez Puerta Del Sur Grupo Hla S.A.
🇪🇸Jerez De La Frontera, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Parc Tauli Hospital Universitari
🇪🇸Sabadell, Spain
Hospital Clinic De Barcelona
🇪🇸Barcelona, Spain
Hospital Clinico Universitario De Valencia
🇪🇸Valencia, Spain
Hospital Universitario Central De Asturias
🇪🇸Oviedo, Spain
Hospital Universitario De La Princesa🇪🇸Madrid, SpainFernando SuarezSite contact+34915202200fsuarezsipmann@gmail.com