E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The main objective of this pilot trial is to evaluate the effect of metoprolol on biological correlates of benefit of this therapy (inflammatory markers in blood and bronchoalveolar mini-lavage, mini-BAL). In addition, it will study cardiopulmonary hemodynamics to assess the impact of metoprolol administration in the context of respiratory distress in COVID-19 |
El objetivo principal de este ensayo piloto es evaluar el efecto de metoprolol en correlatos biológicos de beneficio de esta terapia (marcadores inflamatorios en sangre y minilavado broncoalveolar, mini-BAL). Además, estudiará la hemodinámica cardiopulmonar para evaluar el impacto de la administración de metoprolol en el contexto de distrés respiratorio en COVID-19. |
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E.1.1.1 | Medical condition in easily understood language |
exploratory pilot study that aims to determine the effect of the administration of metoprolol i.v. in inflammation parameters related to neutrophil activation in the lung |
estudio piloto exploratorio que tiene como objetivo determinar el efecto de la administración de metoprolol i.v. en los parámetros de inflamación relacionados conactivación de neutrófilos en pulmón. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of this pilot trial is to evaluate the effect of metoprolol on biological correlates of benefit of this therapy (inflammatory markers in blood and bronchoalveolar mini-lavage, mini-BAL). In addition, it will study cardiopulmonary hemodynamics to assess the impact of metoprolol administration in the context of respiratory distress in COVID-19 |
El objetivo principal de este ensayo piloto es evaluar el efecto de metoprolol en correlatos biológicos de beneficio de esta terapia (marcadores inflamatorios en sangre y minilavado broncoalveolar, mini-BAL). Además, estudiará la hemodinámica cardiopulmonar para evaluar el impacto de la administración de metoprolol en el contexto de distrés respiratorio en COVID-19. |
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E.2.2 | Secondary objectives of the trial |
The study will be considered to meet the safety objective as long as no patient out of the 10 randomized to metoprolol i.v. develop cardiogenic shock, defined as IC ≤2.2 L / m / m2 + invasive systolic pressure <90 mmHg maintained in two measurements separated by 5 minutes |
Se considerará que el estudio cumple el objetivo de seguridad siempre que ningún paciente de los 10 aleatorizados a metoprolol i.v. desarrolle shock cardiogénico, definido como IC ≤2,2 L/m/m2+ presión sistólica invasiva <90 mmHg mantenida en dos determinaciones separadas por 5 minutos |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- ≥18 years and <80 years - Admission to ICU ≤72hr at the time of inclusion - Hospital admission ≤5 days at the time of inclusion - Invasive mechanical ventilation ≤72hr - COVID-19 + (diagnosis by PCR in nasal lavage / bronchoalveolar lavage)) - Invasive management (Orotracheal intubation and invasive monitoring) - Heart rate ≥80 bpm |
- ≥18 años y <80 años - Ingreso en UVI ≤72hr en el momento de inclusión - Ingreso en hospital ≤5 días en el momento de inclusión - Ventilación mecánica invasiva ≤72hr - COVID-19 + (diagnóstico por PCR en lavado nasal/lavado broncoalveolar)) - Manejo invasivo (Intubación orotraqueal y monitorización invasiva) - Frecuencia cardiaca ≥80 lpm |
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E.4 | Principal exclusion criteria |
- Known allergy or hypersensitivity to metoprolol tartrate or other beta-blockers - Cardiac index (CI) ≤2.5 L / m / m2 - Pulmonary capillary pressure (PCP) ≥15 mmHg - Invasive systolic blood pressure (SBP) <110 mmHg - Need for dobutamine due to pump failure in the previous 48 hours - LVEF <50% - RV systolic dysfunction in visual estimation - Significant valve disease (moderate-severe). - Patients with previous moderate or severe COPD / ASMA - Previous treatment with beta-blockers - Associated pulmonary thromboembolism. |
- Alergia o hipersensibilidad conocidas a metoprolol tartrato o a otros betabloqueantes - Índice cardiaco (IC) ≤2,5 L/m/m2 - Presión capilar pulmonar (PCP) ≥15 mmHg - Presión arterial sistólica (PAS) invasiva <110 mmHg - Necesidad de dobutamina por fallo de bomba en las 48 horas previas - FEVI <50% - Disfunción sistólica de VD en estimación visual - Valvulopatía significativa (moderada-severa). - Pacientes con EPOC/ASMA moderada o severa previas - Tratamiento previo con betabloqueantes - Tromboembolismo pulmonar asociado. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Inflammatory markers in BAL (neutrophil activation and NETs production) 2. Inflammatory markers in blood (neutrophil activation and NETs production) 3. Incidence of hemodynamic deterioration |
1. Marcadores inflamatorios en lavado broncoalveolar (activación de neutrófilos y producción de NETs) 2. Marcadores inflamatorios en sangre periférica broncoalveolar (activación de neutrófilos y producción de NETs) 3. Indicencia de deterioro hemodinámico |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Clinical evolution (days of mechanical ventilation, days of admission, mortality) |
1. Evolución clínica (días de ventilación mecánica, días de ingreso, mortalidad) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
index hospitalization period |
periodo de ingreso hospitalario |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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The main objective of the study is to study the trajectory of inflammation markers, neutrophils and NETs in blood and mini-BAL of both groups, before and after 3 days treatment |
El objetivo principal del estudio es estudiar la trayectoria de marcadores de inflamación, neutrófilos y NETs en sangre y mini-BAL de ambos grupos, antes y después de los 3 días de tratamiento |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |