Clinical trial NCT05847517: Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER)
Sponsor class: OTHER_GOV
Collaborators: name: European Commission
name: Instituto de Salud Carlos III
First posted: 2023-05-06
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: days alive and free of invasive mechanical ventilation during the first 28 days.
timeFrame: 28 days
Secondary outcomes:
measure: All-cause death at day 28 after randomization
timeFrame: 28 days
measure: Ventilator-free days at 28 days
timeFrame: 28 days
measure: Intensive care unit days of admission
timeFrame: 3 months
measure: Quality of life score
timeFrame: at 3 months
measure: Arterial oxygenation
timeFrame: on day 8
measure: Change in arterial oxygenation
timeFrame: 8 days
Other outcomes:
Locations:
city: Jerez
country: Spain
facility: Hospital Universitario de Jerez de La Frontera
state: Cadiz
city: Toledo
country: Spain
facility: Hospital Universitario de Toledo
state: Castilla-La Mancha
city: Barcelona
country: Spain
facility: Hospital Clinic
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Parc Taulí
state: Cataluña
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz University Hospital
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital de Getafe
city: Madrid
country: Spain
facility: Hospital General de Villalba
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital Rey Juan Carlos
Study officials:
affiliation: CNIC &amp; Fundación Jiménez Díaz University Hospital
name: Borja Ibanez, MD PhD FESC
role: PRINCIPAL_INVESTIGATOR
References: