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    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7294   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2022-002494-28
    Sponsor's Protocol Code Number:6
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2023-03-24
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2022-002494-28
    A.3Full title of the trial
    Randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of intravenous metoprolol in patients with Acute Respiratory Distress Syndrome (ARDS)
    Ensayo clínico aleatorizado controlado frente a placebo, doble ciego, para evaluar la eficacia de metoprolol intravenoso en pacientes con Síndrome de Distrés Respiratorio Agudo (SDRA)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical trial to assess the efficacy of intravenous metoprolol in patients with Acute Respiratory Distress Syndrome (ARDS).
    Ensayo clínico para evaluar la eficacia de metoprolol intravenoso en pacientes con Síndrome de Distrés Respiratorio Agudo (SDRA).
    A.3.2Name or abbreviated title of the trial where available
    MAIDEN
    MAIDEN
    A.4.1Sponsor's protocol code number6
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorConsorcio Centro de Investigacion Biomedica en Red, (CIBER)
    B.1.3.4CountrySpain
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportInstituto de Salud Carlos IIII
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationConsorcio Centro de Investigacion Biomedica en Red, (CIBER)
    B.5.2Functional name of contact pointRebeca Colorado Sacristan
    B.5.3 Address:
    B.5.3.1Street AddressInstituto de Salud Carlos III, Avda. Monforte de Lemos, 3-5 | Pabellón 11
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28029
    B.5.3.4CountrySpain
    B.5.4Telephone number+34918222874
    B.5.6E-mailproyectos@ciberisciii.es
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Beloken
    D.2.1.1.2Name of the Marketing Authorisation holderBeloken
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMetoprolol tartrate
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Intensive Care Unit patients with Acute Respiratory Distress Syndrome (ARDS)
    Pacientes ingresados en la Unidad de Cuidados Intensivos con Síndrome de Distrés Respiratorio Agudo (SDRA)
    E.1.1.1Medical condition in easily understood language
    Intensive Care Unit patients with Acute Respiratory Distress Syndrome (ARDS)
    Pacientes ingresados en la Unidad de Cuidados Intensivos con Síndrome de Distrés Respiratorio Agudo (SDRA)
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10003083
    E.1.2Term ARDS
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate the efficacy of IV metoprolol 15 mg in recently intubated ARDS patients, evaluating survival and days free of invasive mechanical ventilation during the first 28 days.
    Demostrar la eficacia de metoprolol IV 15 mg en pacientes con SDRA recientemente intubados, evaluando la supervivencia y días libres de ventilación mecánica invasiva durante los primeros 28 días.
    E.2.2Secondary objectives of the trial
    • Impact of metoprolol administration in ARDS patients on blood oxygenation.
    • Effect of the administration of metoprolol in patients with moderate-severe ARDS on systemic inflammation. To characterize the inflammatory cell profiles in patients, and to compare between treatment arms.
    • Establish a collection of samples (including a large RNA/microRNA/DNA library) from patients with moderate-severe ARDS that can be exploited for mechanistic studies.
    • To study the impact of polymorphisms in the β1AR Arg389Gly (A/A, A/G, G/G) gene on the clinical benefit of metoprolol in patients with moderate-severe ARDS.
    • Study the transcriptomic signatures in circulating cells of ARDS patients that are associated with a better long-term prognosis.
    • Impacto de la administración de metoprolol en pacientes con SDRA sobre la oxigenación de la sangre.
    • Efecto de la administración de metoprolol en pacientes con SDRA moderado-severo sobre la inflamación sistémica. Caracterizar los perfiles celulares inflamatorios en los pacientes, y comparar entre los brazos de tratamiento.
    • Establecer una colección de muestras (incluida una gran biblioteca de ARN/microARN/ADN) de pacientes con SDRA moderado-severo que pueda ser explotada para realizar estudios mecanísticos.
    • Estudiar el impacto de polimorfismos en el gen β1AR Arg389Gly (A/A, A/G, G/G) en el beneficio clínico de metoprolol en pacientes con SDRA moderado-severo.
    • Estudiar las firmas de transcriptómica en las células circulantes de los pacientes con SDRA que se asocian con un mejor pronóstico a largo plazo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients (≥18 years and <80 years) with a clinical diagnosis of ARDS of any etiology (pneumonia, including SARS-CoV-2, sepsis, pancreatitis, due to bronchial aspiration and trauma) admitted to the ICU.
    2. Orotracheal intubation (OTI) and mechanical ventilation within 72 hours prior to randomization.
    3. Moderate-severe ARDS (PaO2/FiO2: ≤200 mmHg under standardized conditions (PEEP≥5 cm H2O).
    4. Heart rate ≥ 60 bpm.
    5. Invasive systolic blood pressure ≥ 110 mmHg.
    1. Pacientes (≥18 años y < 80 años) con diagnóstico clínico de SDRA de cualquier etiología (neumonía, incluyendo SARS-CoV-2, sepsis, pancreatitis, por broncoaspiración y traumatismos) que ingresan en la UCI.
    2. Intubación orotraqueal (IOT) y ventilación mecánica dentro de las 72 horas previas a la aleatorización.
    3. SDRA moderado-severo (PaO2/FiO2: ≤200 mmHg en condiciones estandarizadas (PEEP≥5 cm H2O).
    4. Frecuencia cardíaca ≥ 60 lpm.
    5. Presión arterial sistólica invasiva ≥ 110 mmHg.
    E.4Principal exclusion criteria
    1. Ingreso hospitalario prolongado antes de la aleatorización (es decir, ≥7 días en el momento de la aleatorización).
    2. Fracción de eyección ventricular izquierda reducida (FEVI <50%).
    3. Esperanza de vida por otros procesos (cáncer, enfermedades degenerativas…) inferior a 6 meses.
    4. Disfunción sistólica del ventrículo derecho (VD).
    5. Insuficiencia cardíaca aguda concomitante (índice cardíaco ≤2,5 L/m2 o presión capilar pulmonar ≥15 mmHg o sospecha clínica).
    6. Presión arterial invasiva persistente <110 mmHg a pesar de los agentes vasopresores
    8. Uso de noradrenalina a concentraciones superiores a 0,2 µg/kg/min en el momento de la aleatorización.
    9. Uso de dobutamina en las 48 horas previas a la aleatorización.
    10. Embolia pulmonar concomitante.
    11. Enfermedad arterial periférica severa conocida.
    12. Asma conocida antes del ingreso (con tratamiento broncodilatador activo).
    13. Tratamiento activo con betabloqueantes antes del ingreso (es decir, en los 3 meses anteriores).
    6. Ingreso hospitalario prolongado antes de la aleatorización (es decir, ≥7 días en el momento de la aleatorización).
    7. Fracción de eyección ventricular izquierda reducida (FEVI <50%).
    8. Esperanza de vida por otros procesos (cáncer, enfermedades degenerativas…) inferior a 6 meses.
    9. Disfunción sistólica del ventrículo derecho (VD).
    10. Insuficiencia cardíaca aguda concomitante (índice cardíaco ≤2,5 L/m2 o presión capilar pulmonar ≥15 mmHg o sospecha clínica).
    11. Presión arterial invasiva persistente <110 mmHg a pesar de los agentes vasopresores
    12. Uso de noradrenalina a concentraciones superiores a 0,2 µg/kg/min en el momento de la aleatorización.
    13. Uso de dobutamina en las 48 horas previas a la aleatorización.
    14. Embolia pulmonar concomitante.
    15. Enfermedad arterial periférica severa conocida.
    16. Asma conocida antes del ingreso (con tratamiento broncodilatador activo).
    17. Tratamiento activo con betabloqueantes antes del ingreso (es decir, en los 3 meses anteriores).
    E.5 End points
    E.5.1Primary end point(s)
    • Survival in the 28 days after randomization.
    • Days free of mechanical ventilation in the 28 days after randomization.
    • Days of admission to the ICU.
    • Days from randomization to hospital discharge
    • Cumulative mortality from any cause during 3 months of follow-up after randomization.
    • Quality of life 3 months after randomization.
    • Supervivencia en los 28 días tras la aleatorización.
    • Días libres de ventilación mecánica en los 28 días tras la aleatorización.
    • Días de ingreso en UCI.
    • Días desde aleatorización a alta hospitalaria
    • Mortalidad de cualquier causa acumulada durante 3 meses de seguimiento tras aleatorización.
    • Calidad de vida 3 meses después de la aleatorización.
    E.5.1.1Timepoint(s) of evaluation of this end point
    28 days after randomization.
    28 días tras la aleatorización.
    E.5.2Secondary end point(s)
    • PEEP (cmH2O)
    • Tidal volume (mL)
    • Plateau pressure (cmH2O)
    • Respiratory rate (breaths/min)
    • FiO2 (%)
    • pH
    • PaO2 (mmH2O)
    • PaCO2 (mmH2O)
    • Sat O2 (%)
    • Quantitative assessment in percentage (approx.) of alveolar macrophages, columnar cells, neutrophil polymorphonuclear cells, eosinophil polymorphonuclear cells and lymphocytes.
    • β1AR Arg389Gly polymorphism (Arg/Arg vs. Arg/Gly and Gly/Gly).
    • PEEP (cmH2O)
    • Volumen tidal (mL)
    • Presión Plateau (cmH2O)
    • Frecuencia respiratoria (resp/min)
    • FiO2 (%)
    • pH
    • PaO2 (mmH2O)
    • PaCO2 (mmH2O)
    • Sat O2 (%)
    • Valoración cuantitativa en porcentaje (aprox.) de macrófagos alveolares, células cilíndricas, polimorfonucleares neutrófilos, polimorfonucleares eosinófilos y linfocitos.
    • Polimorfismo β1AR Arg389Gly (Arg/Arg vs. Arg/Gly y Gly/Gly).
    E.5.2.1Timepoint(s) of evaluation of this end point
    28 days after randomization.
    28 días tras la aleatorización.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned11
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    Última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 350
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 350
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    ICU patients with sedation due to intubation, it will not be possible to obtain the patient's IC. A family will be contacted as legal representative, the intention to include him/her.
    Pacientes en UVI con sedación por su intubación otrotraqueal, no será posible obtener el CI del paciente. Se contactará con un familiar como representante legal , se informará la intención de incluirle.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state350
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    According to standard care
    Acorde con la práctica clínica
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-05-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-04-25
    P. End of Trial
    P.End of Trial StatusOngoing
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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