Randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy ofintravenous metoprolol in patients with Acute Respiratory Respiratory Distress Syndrome(ARDS).
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.
Drug: Metoprolol Injection
A dilution of 15 mg Metoprolol tartrate in 100 ml saline shall be performed and infused
for 10 minutes. No dose reduction or increase is allowed. Systolic blood pressure and
heart rate shall be measured 3 and 6 minutes after starting the infusion.
In case of a consistent drop in systolic blood pressure or heart rate, the infusion shall
be stopped and the infusion noted.
Drug: saline 0.9%
A dilution of 0.9% sodium chloride in 100 ml saline shall be performed and infused for 10
minutes. No dose reduction or increase is allowed. Systolic blood pressure and heart rate
shall be measured 3 and 6 minutes after starting the infusion.
In case of a consistent drop in systolic blood pressure below 110 mmHg or heart rate
below 60 bpm, the infusion shall be stopped and the infusion noted.
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).
- 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).
Hospital Universitario de Jerez de La Frontera
Jerez, Cadiz, Spain
Hospital Universitario de Toledo
Toledo, Castilla-La Mancha, Spain
Hospital Clinic
Barcelona, Cataluña, Spain
Hospital Parc Taulí
Barcelona, Cataluña, Spain
Fundación Jiménez Díaz University Hospital
Madrid, Spain
Hospital Clínico San Carlos
Madrid, Spain
Hospital de Getafe
Madrid, Spain
Hospital General de Villalba
Madrid, Spain
Hospital La Paz
Madrid, Spain
Hospital Rey Juan Carlos
Madrid, Spain
Marta Delgado
+34 91 550 48 00
ensayomaiden@gmail.com
Projects Department (CIBER)
+34 91 822 28 74
proyectos@ciberisciii.es
Borja Ibanez, MD PhD FESC, Principal Investigator
CNIC & Fundación Jiménez Díaz University Hospital