Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)

NCT ID: NCT05847517

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-13
• Study Completion Date: 2027-12-31

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.

Conditions

Acute Respiratory Distress Syndrome (ARDS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Metoprolol

Participants will be administered IV Metoprolol tartrate 15 mg (3 ampoules of 5 ml) diluted in 100 ml of saline.

Group Type: ACTIVE_COMPARATOR

Metoprolol Injection

Intervention Type: DRUG

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.

Saline

Participants will be administered IV saline (0.9% sodium chloride) (3 ampoules of 5 ml) diluted in 100 ml of saline.

Group Type: PLACEBO_COMPARATOR

saline 0.9%

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Commission

OTHER

Sponsor Role: collaborator

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Consorcio Centro de Investigación Biomédica en Red (CIBER)

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Borja Ibanez, MD PhD FESC

Role: PRINCIPAL_INVESTIGATOR

CNIC &amp; Fundación Jiménez Díaz University Hospital

Locations

Hospital Universitario de Jerez de La Frontera

Jerez de la Frontera, CADIZ, Spain

Site Status: ACTIVE_NOT_RECRUITING

Hospital Universitario de Toledo

Toledo, Castille-La Mancha, Spain

Site Status: NOT_YET_RECRUITING

Hospital Clinic

Barcelona, Catalonia, Spain

Site Status: ACTIVE_NOT_RECRUITING

Hospital Parc Taulí

Barcelona, Catalonia, Spain

Site Status: NOT_YET_RECRUITING

Fundación Jiménez Díaz University Hospital

Madrid, Madrid, Spain

Site Status: RECRUITING

Hospital Clínico San Carlos

Madrid, Madrid, Spain

Site Status: ACTIVE_NOT_RECRUITING

Hospital de Getafe

Madrid, Madrid, Spain

Site Status: NOT_YET_RECRUITING

Hospital General de Villalba

Madrid, Madrid, Spain

Site Status: ACTIVE_NOT_RECRUITING

Hospital La Paz

Madrid, Madrid, Spain

Site Status: ACTIVE_NOT_RECRUITING

Hospital Rey Juan Carlos

Madrid, Madrid, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Marta Delgado

Role: CONTACT

ensayomaiden@gmail.com

+34 91 550 48 00

Projects Department (CIBER)

Role: CONTACT

proyectos@ciberisciii.es

+34 91 822 28 74

Facility Contacts

Sandra Gómez-Talavera, MD

Role: primary

Other Identifiers

MAIDEN

Identifier Type: -

Identifier Source: org_study_id