Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)

NCT05847517 | Recruiting Phase 3 DMC

• 1 other identifier: MAIDEN
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 10

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).

Conditions

Acute Respiratory Distress Syndrome (ARDS)

Keywords

metoprolol; beta-blockers; sepsis; orotracheal intubation; Pathologic Processes; Respiratory Disease; Neutrophil Extracellular Traps; platelet aggregation; diffuse alveolar damage; neutrophil infiltration; Pulmonary Inflammation; pancreatitis; Severe Acute Respiratory Syndrome-Corona Virus-2; Drug-Related Side Effects and Adverse Reactions

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• All-cause death at day 28 after randomization

  28 days

• Ventilator-free days at 28 days

  28 days

• Intensive care unit days of admission

  3 months

• Quality of life score

  at 3 months

• Arterial oxygenation

  on day 8

Study Arms (2)

Metoprolol

ACTIVE COMPARATOR

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

Drug: Metoprolol Injection

Saline

PLACEBO COMPARATOR

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%

Interventions

Metoprolol Injection 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.

Metoprolol

saline 0.9% 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.

Saline

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• Consorcio Centro de Investigación Biomédica en Red (CIBER): lead
• European Commission: collaborator
• Instituto de Salud Carlos III: collaborator

Study Sites (10)

Hospital Universitario de Jerez de La Frontera

Jerez de la Frontera, CADIZ, Spain

ACTIVE NOT RECRUITING

Hospital Universitario de Toledo

Toledo, Castille-La Mancha, Spain

NOT YET RECRUITING

Hospital Clinic

Barcelona, Catalonia, Spain

ACTIVE NOT RECRUITING

Hospital Parc Taulí

Barcelona, Catalonia, Spain

NOT YET RECRUITING

Fundación Jiménez Díaz University Hospital

Madrid, Madrid, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, Madrid, Spain

ACTIVE NOT RECRUITING

Hospital de Getafe

Madrid, Madrid, Spain

NOT YET RECRUITING

Hospital General de Villalba

Madrid, Madrid, Spain

ACTIVE NOT RECRUITING

Hospital La Paz

Madrid, Madrid, Spain

ACTIVE NOT RECRUITING

Hospital Rey Juan Carlos

Madrid, Madrid, Spain

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome; Sepsis; Pathologic Processes; Respiration Disorders; Pneumonia; Pancreatitis; Drug-Related Side Effects and Adverse Reactions

Interventions

Metoprolol; Sodium Chloride

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Pancreatic Diseases; Digestive System Diseases; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Borja Ibanez, MD PhD FESC

  CNIC &amp; Fundación Jiménez Díaz University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta Delgado

CONTACT

+34 91 550 48 00; ensayomaiden@gmail.com

Projects Department (CIBER)

CONTACT

+34 91 822 28 74; proyectos@ciberisciii.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both metoprolol and saline are supplied in 5 ml ampoules of the same shape, structure and colour
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Randomization (1:1) will be stratified according to the severity of ARDS and by participating centre: * Moderate (PaO2/FiO2 of 100-200 mmHg). * Severe (PaO2/FiO2 ≤100 mmHg).

Study Record Dates

• First Submitted: April 21, 2023
• First Posted: May 6, 2023
• Study Start: August 13, 2024
• Primary Completion: September 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10)