Back to resultsMetoprolol in Acute Respiratory Distress Syndrome (MAIDEN) (MAIDEN)
Primary Purpose
Acute Respiratory Distress Syndrome (ARDS)
Status
Not yet recruiting
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Metoprolol Injection
saline 0.9%
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Distress Syndrome (ARDS) focused on measuring 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
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).
Sites / Locations
- Hospital SAS de Jerez
- Hospital Universitario de Toledo
- Hospital Clinic
- Hospital Parc Taulí
- Fundación Jiménez Díaz University Hospital
- Hospital Clínico San Carlos
- Hospital de Getafe
- Hospital General de Villalba
- Hospital La Paz
- Hospital Ramón y Cajal
- Hospital Rey Juan Carlos
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Metoprolol
Saline
Arm Description
Participants will be administered IV Metoprolol tartrate 15 mg (3 ampoules of 5 ml) diluted in 100 ml of saline.
Participants will be administered IV saline (0.9% sodium chloride) (3 ampoules of 5 ml) diluted in 100 ml of saline.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
All-cause death at day 28 after randomization
cumulative incidence of death from any cause
Ventilator-free days at 28 days
number of days without mechanical ventilation during the firs 28 days
Intensive care unit days of admission
Number of days admitted at the intensive care unit
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.
Arterial oxygenation
Mean arterial oxygen saturation (PaO2/FiO2)
Change in arterial oxygenation
Mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8
Full Information
NCT ID
NCT05847517
First Posted
April 21, 2023
Last Updated
August 31, 2023
Sponsor
Consorcio Centro de Investigación Biomédica en Red (CIBER)
Collaborators
European Commission, Instituto de Salud Carlos III
1. Study Identification
Unique Protocol Identification Number
NCT05847517
Brief Title
Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)
Acronym
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
December 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Consorcio Centro de Investigación Biomédica en Red (CIBER)
Collaborators
European Commission, Instituto de Salud Carlos III
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Both metoprolol and saline are supplied in 5 ml ampoules of the same shape, structure and colour
Allocation
Randomized
Enrollment
350 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metoprolol
Arm Type
Active Comparator
Arm Description
Participants will be administered IV Metoprolol tartrate 15 mg (3 ampoules of 5 ml) diluted in 100 ml of saline.
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
Participants will be administered IV saline (0.9% sodium chloride) (3 ampoules of 5 ml) diluted in 100 ml of saline.
Intervention Type
Drug
Intervention Name(s)
Metoprolol Injection
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
saline 0.9%
Intervention Description
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.
Primary Outcome Measure Information:
Title
days alive and free of invasive mechanical ventilation during the first 28 days.
Description
Hierarchical composite outcome "Alive and ventilator-free days at 28 days" (win ratio approach)
Time Frame
28 days
Secondary Outcome Measure Information:
Title
All-cause death at day 28 after randomization
Description
cumulative incidence of death from any cause
Time Frame
28 days
Title
Ventilator-free days at 28 days
Description
number of days without mechanical ventilation during the firs 28 days
Time Frame
28 days
Title
Intensive care unit days of admission
Description
Number of days admitted at the intensive care unit
Time Frame
3 months
Title
Quality of life score
Description
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.
Time Frame
at 3 months
Title
Arterial oxygenation
Description
Mean arterial oxygen saturation (PaO2/FiO2)
Time Frame
on day 8
Title
Change in arterial oxygenation
Description
Mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8
Time Frame
8 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elba Barroso Fuentes, BS
Phone
+34 91 550 48 00
Email
maiden.elba.barroso@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Projects Department (CIBER)
Phone
+34 91 822 28 74
Email
proyectos@ciberisciii.es
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Borja Ibanez, MD PhD FESC
Organizational Affiliation
CNIC & Fundación Jiménez Díaz University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital SAS de Jerez
City
Jerez De La Frontera
State/Province
Andalucía
Country
Spain
Facility Name
Hospital Universitario de Toledo
City
Toledo
State/Province
Castilla-La Mancha
Country
Spain
Facility Name
Hospital Clinic
City
Barcelona
State/Province
Cataluña
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoni Torres Marti
Facility Name
Hospital Parc Taulí
City
Barcelona
State/Province
Cataluña
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Oriol Roca Gas
Facility Name
Fundación Jiménez Díaz University Hospital
City
Madrid
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra Gómez-Talavera, MD
First Name & Middle Initial & Last Name & Degree
Arnoldo Santos-Oviedo, MD PhD
Facility Name
Hospital Clínico San Carlos
City
Madrid
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fernando Martínez Sagasti
Facility Name
Hospital de Getafe
City
Madrid
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José Ángel Lorente Balanza
Facility Name
Hospital General de Villalba
City
Madrid
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victoria Adriana Benítez Ferreiro
Facility Name
Hospital La Paz
City
Madrid
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José Manuel Añón Elizade
Facility Name
Hospital Ramón y Cajal
City
Madrid
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raúl De Pablo Sánchez
Facility Name
Hospital Rey Juan Carlos
City
Madrid
Country
Spain
12. IPD Sharing Statement
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Metoprolol in Acute Respiratory Distress Syndrome (MAIDEN)
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