Clinical trial
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).
Name
MAIDEN
Description
Randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy of intravenous metoprolol in patients with Acute Respiratory Respiratory Distress Syndrome (ARDS).
Trial arms
Trial start
2023-11-01
Estimated PCD
2025-09-01
Trial end
2027-12-01
Status
Not yet recruiting
Phase
Early phase I
Treatment
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.
Arms:
Metoprolol
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.
Arms:
Saline
Size
350
Primary endpoint
days alive and free of invasive mechanical ventilation during the first 28 days.
28 days
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).
* 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).
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomization (1:1) will be stratified according to the severity of ARDS and by participating centre:\n\n* Moderate (PaO2/FiO2 of 100-200 mmHg).\n* Severe (PaO2/FiO2 ≤100 mmHg).', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Both metoprolol and saline are supplied in 5 ml ampoules of the same shape, structure and colour', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 350, 'type': 'ESTIMATED'}}
Updated at
2023-09-01
Product
MetoprololIndication
Acute Respiratory Distress SyndromeProduct
Saline 0.9%