Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorcio Centro De Investigacion Biomedica En Red

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

completed 3 Oct 2025

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515813-17-00

EudraCT number

2022-002494-28

ClinicalTrials.gov

NCT05847517

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Days alive and free of invasive mechanical ventilation during the first 28 days. [ Time Frame: 28 days ]
Hierarchical composite outcome "Alive and ventilator-free days at 28 days" (win ratio approach)

Secondary objectives 6

1. All-cause death at day 28 after randomization [ Time Frame: 28 days ] cumulative incidence of death from any cause
2. Ventilator-free days at 28 days [ Time Frame: 28 days ] number of days without mechanical ventilation during the firs 28 days
3. Intensive care unit days of admission [ Time Frame: 3 months ] Number of days admitted at the intensive care unit
4. Quality of life score [ Time Frame: at 3 months ] 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 posible health.
5. Arterial oxygenation [ Time Frame: on day 8 ] Mean arterial oxygen saturation (PaO2/FiO2)
6. Change in arterial oxygenation [ Time Frame: 8 days ] Mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8

Conditions and MedDRA coding

Acute Respiratory Distress Syndrome (ARDS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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.
2. Orotracheal intubation (OTI) and mechanical ventilation within 72 hours prior to randomisation.
3. Moderate-severe ARDS (PaO2/FiO2: ≤200 mmHg under standardised conditions (PEEP≥5 cm H2O).
4. Heart rate ≥ 60 bpm.
5. Invasive systolic blood pressure ≥ 110 mmHg.

Exclusion criteria 15

1. Prolonged hospital admission prior to randomisation (i.e. ≥7 days at the time of randomisation).
2. Reduced left ventricular ejection fraction (LVEF <50%).
3. Life expectancy due to other processes (cancer, degenerative diseases, etc.) of les tan 6 months.
4. Right ventricular (RV) systolic dysfunction.
5. Concomitant acute heart failure (cardiac index ≤2.5 L/m2 or pulmonary capillary pressure ≥15 mmHg or clinical suspicion).
6. 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 inclusión criterion.
7. Pregnant or breastfeeding women.
8. Cardiogenic shock.
9. Persistent invasive blood pressure <110 mmHg despite vasopresor agents.
10. Use of noradrenaline at concentrations greater than 0.2 µg/kg/min at the time of the randomisation.
11. Use of dobutamine within 48 hours before randomisation.
12. Concomitant pulmonary embolism.
13. Known severe peripheral arterial disease.
14. Known asthma before admission (with active bronchodilator therapy).
15. Active beta-blocker treatment prior to admission (i.e. within 3 months prior to admission).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Days alive and free of invasive mechanical ventilation during the first 28 days. [ Time Frame: 28 days ] Hierarchical composite outcome "Alive and ventilator-free days at 28 days" (win ratio approach)

Secondary endpoints 6

1. All-cause death at day 28 after randomization [ Time Frame: 28 days ] cumulative incidence of death from any cause
2. Ventilator-free days at 28 days [ Time Frame: 28 days ] number of days without mechanical ventilation during the firs 28 days
3. Intensive care unit days of admission [ Time Frame: 3 months ] Number of days admitted at the intensive care unit
4. Quality of life score [ Time Frame: at 3 months ] 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 ítems).
5. Arterial oxygenation [ Time Frame: on day 8 ] Mean arterial oxygen saturation (PaO2/FiO2)
6. Change in arterial oxygenation [ Time Frame: 8 days ] Mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorcio Centro De Investigacion Biomedica En Red

Sponsor organisation

Consorcio Centro De Investigacion Biomedica En Red

Address

Pab 11, Avenida De Monforte De Lemos 3-5 Avenida De Monforte De Lemos 3-5

City

Madrid

Postcode

28029

Country

Spain

Scientific contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Projects Department (CIBER)

Public contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Projects Department (CIBER)

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications