Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN) (MAIDEN)

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).

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

Study Overview

• Status: Terminated
• Conditions: Acute Respiratory Distress Syndrome (ARDS)
• Intervention / Treatment: Drug: Metoprolol Injection; Drug: saline 0.9%

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos
  • Madrid, Spain, 28905
    • Hospital Universitario de Getafe
  • Madrid, Spain, 28933
    • Hospital Universitario Rey Juan Carlos
  • Madrid, Spain, 28400
    • Hospital Universitario General de Villalba
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Castille-La Mancha
    • Toledo, Castille-La Mancha, Spain, 45007
      • Complejo Hospitalario Universitario de Toledo
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clínic de Barcelona
    • Barcelona, Catalonia, Spain, 08208
      • Consorci Corporacio Sanitaria Parc Tauli
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • Hospital Universitario Jerez de la Frontera
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metoprolol; Participants will be administered IV Metoprolol tartrate 15 mg (3 ampoules of 5 ml) diluted in 100 ml of saline.	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.
Placebo Comparator: Saline; Participants will be administered IV saline (0.9% sodium chloride) (3 ampoules of 5 ml) diluted in 100 ml of saline.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
days alive and free of invasive mechanical ventilation during the first 28 days.	Hierarchical composite outcome "Alive and ventilator-free days at 28 days" (win ratio approach)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death at day 28 after randomization	cumulative incidence of death from any cause	28 days
Ventilator-free days at 28 days	number of days without mechanical ventilation during the firs 28 days	28 days
Intensive care unit days of admission	Number of days admitted at the intensive care unit	3 months
Arterial oxygenation	Mean arterial oxygen saturation (PaO2/FiO2)	on day 8
Quality of life score	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.	at 3 months
Change in arterial oxygenation	Mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8	8 days

Collaborators and Investigators

• Sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER)
• Collaborators: Instituto de Salud Carlos III; European Commission
• Investigators: Principal Investigator: Borja Ibanez, MD PhD FESC, CNIC & Fundación Jiménez Díaz University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2024
• Primary Completion (Actual): October 6, 2025
• Study Completion (Actual): October 6, 2025

Study Registration Dates

• First Submitted: April 21, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pathologic Processes; platelet aggregation; sepsis; pancreatitis; Drug-Related Side Effects and Adverse Reactions; orotracheal intubation; beta-blockers; Respiratory Disease; Pulmonary Inflammation; metoprolol; Neutrophil Extracellular Traps; diffuse alveolar damage; neutrophil infiltration; Severe Acute Respiratory Syndrome-Corona Virus-2
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Digestive System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Lung Diseases; Pancreatic Diseases; Chemically-Induced Disorders; Pathological Conditions, Signs and Symptoms; Respiratory Distress Syndrome; Pancreatitis; Pneumonia; Sepsis; Drug-Related Side Effects and Adverse Reactions; Pathologic Processes; Respiration Disorders; Organic Chemicals; Amines; Inorganic Chemicals; Chlorine Compounds; Alcohols; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Sodium Compounds; Chlorides; Hydrochloric Acid; Metoprolol; Sodium Chloride
• Other Study ID Numbers: MAIDEN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No