Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)

Acute Respiratory Distress Syndrome (ARDS) Clinical Trial

— 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).

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05847517
• Other study ID #: MAIDEN
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 2023
• Est. completion date: December 2027

Study information

• Verified date: May 2023
• Source: Consorcio Centro de Investigación Biomédica en Red (CIBER)
• Contact: Elba Barroso Fuentes, BS
• Phone: +34 91 550 48 00
• Email: maiden.elba.barroso[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 350
• Est. completion date: December 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome (ARDS)
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
Spain	Hospital Clinic	Barcelona	Cataluña
Spain	Hospital Parc Taulí	Barcelona	Cataluña
Spain	Hospital SAS de Jerez	Jerez De La Frontera	Andalucía
Spain	Fundación Jiménez Díaz University Hospital	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital de Getafe	Madrid
Spain	Hospital General de Villalba	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Rey Juan Carlos	Madrid
Spain	Hospital Universitario de Toledo	Toledo	Castilla-La Mancha

Sponsors (3)

Lead Sponsor	Collaborator
Consorcio Centro de Investigación Biomédica en Red (CIBER)	European Commission, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

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