Using metoprolol to treat patients with Acute Respiratory Distress Syndrome

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).

This study is testing if giving metoprolol to patients with Acute Respiratory Distress Syndrome who are on a ventilator can help them survive better and spend fewer days on the machine.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 350 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER) (Government)
• Locations: 10 sites (Jerez de la Frontera, CADIZ and 9 other locations)
• Trial ID: NCT05847517 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of intravenous metoprolol in patients diagnosed with Acute Respiratory Distress Syndrome (ARDS) who have recently undergone orotracheal intubation and mechanical ventilation. It is a randomized, double-blind, placebo-controlled Phase III trial involving 350 participants across multiple centers. The study aims to assess survival rates and the number of days free from invasive mechanical ventilation over a 28-day period. Participants will receive either metoprolol or a placebo for seven days, with careful monitoring of their condition throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with moderate to severe ARDS who have been intubated and mechanically ventilated within the last 72 hours.

Not a fit: Patients with prolonged hospital stays, significant heart dysfunction, or other severe comorbidities may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and reduce the duration of mechanical ventilation for patients with ARDS.

How similar studies have performed: While the use of beta-blockers in ARDS is a novel approach, previous studies have shown mixed results, indicating the need for further investigation.

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).

Where this trial is running

Jerez de la Frontera, CADIZ and 9 other locations

• 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)

Study contacts

• Principal investigator: Borja Ibanez, MD PhD FESC — CNIC & Fundación Jiménez Díaz University Hospital
• Study coordinator: Marta Delgado

Conditions Acute Respiratory Distress Syndrome; metoprolol; beta-blockers; sepsis; orotracheal intubation; Pathologic Processes; Respiratory Disease; Neutrophil Extracellular Traps