Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)

Phase 3

Recruiting

• Conditions: Acute Respiratory Distress Syndrome (ARDS)
• Interventions: Drug: Metoprolol Injection; Drug: saline 0.9%

• Registration Number: NCT05847517
• Lead Sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER)

Brief Summary

Randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy of intravenous metoprolol in patients with Acute Respiratory Respiratory Distress Syndrome (ARDS).

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.

Study Timeline

• Study First Submitted: 2023-04-21
• Study First Submitted QC: 2023-04-27
• Study First Posted: 2023-05-06
• Study Start: 2024-08-13
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-06
• Last Update Posted: 2025-02-10
• Primary Completion: 2025-09
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 350

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).

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.	28 days	Hierarchical composite outcome "Alive and ventilator-free days at 28 days" (win ratio approach)

Secondary Outcome Measures

Name	Time	Method
Arterial oxygenation	on day 8	Mean arterial oxygen saturation (PaO2/FiO2)
Intensive care unit days of admission	3 months	Number of days admitted at the intensive care unit
All-cause death at day 28 after randomization	28 days	cumulative incidence of death from any cause
Ventilator-free days at 28 days	28 days	number of days without mechanical ventilation during the firs 28 days
Quality of life score	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 items). A scoring algorithm is used to convert the raw scores into the eight dimensions listed above. The scores are transformed to range from zero where the respondent has the worst possible health to 100 where the respondent is in the best possible health.
Change in arterial oxygenation	8 days	Mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8

Trial Locations

Locations (10)

Hospital Parc Taulí; 🇪🇸 Barcelona, Cataluña, Spain

Fundación Jiménez Díaz University Hospital; 🇪🇸 Madrid, Spain

Hospital Universitario de Jerez de La Frontera; 🇪🇸 Jerez, Cadiz, Spain

Hospital de Getafe; 🇪🇸 Madrid, Spain

Hospital La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario de Toledo; 🇪🇸 Toledo, Castilla-La Mancha, Spain

Hospital Clinic; 🇪🇸 Barcelona, Cataluña, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain

Hospital General de Villalba; 🇪🇸 Madrid, Spain

Hospital Rey Juan Carlos; 🇪🇸 Madrid, Spain