E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cardiogenic Shock |
Shock cardiogénico |
|
E.1.1.1 | Medical condition in easily understood language |
Heart failure |
Shock cardiogénico |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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 |
Determine if oral ivabradine in patients with ischemic heart disease, left ventricular ejection fraction depressed with severe acute heart failure (AHF) and indication for intravenous inotropic treatment, reduces pulmonary wedge pressure significantly compared to usual treatment without reducing the cardiac output. |
Determinar si la ivabradina oral en pacientes con cardiopatía isquémica, fracción de eyección de ventrículo izquierdo deprimida con insuficiencia cardiaca aguda (ICA) grave e indicación de tratamiento inotrópico intravenoso, reduce la presión de enclavamiento pulmonar de forma significativa respecto a tratamiento habitual sin reducir el gasto cardíaco. |
|
E.2.2 | Secondary objectives of the trial |
1.Evaluate the safety of ivabradine in patients with severe AHF treated with intravenous catecholamines. We will use parameters such as: development of excessive bradycardia (HR <50 bpm), hypotension (systolic BP <90 mmHg), appearance of ventricular arrhythmias or atrial fibrillation. 2. Evaluate the clinical efficacy of the attenuation of the chronotropic response to catecholamines in the clinical model of severe AHF. We will use surrogate parameters such as: time to inotropic withdrawal, mechanical ventilation time, BNP levels and CRP levels. 3. Analyze total mortality and mortality due to cardiovascular causes in patients with usual treatment or with ivabradine in those patients showing severe AHF who were treated with intravenous catecholamines. 4. Assess the effects of ivabradine on ventricular volumes in the context of severe AHF due to left ventricular dysfunction. |
1. Evaluar la seguridad de la ivabradina en pacientes con ICA grave en tratamiento con catecolaminas intravenosas: aparición de bradicardia excesiva (FC<50 lpm), hipotensión (PA sistólica < 90 mmHg), aparición de arritmias ventriculares o fibrilación auricular. 2. Evaluar la eficacia clínica de la atenuación de la respuesta cronotrópica a las catecolaminas en el modelo clínico de ICA grave. Utilizaremos parámetros subrogados como: tiempo hasta la retirada de inotrópicos, tiempo de ventilación mecánica, niveles de BNP y niveles de PCR. 3. Analizar la mortalidad total y la mortalidad por causa cardiovascular en pacientes con tratamiento habitual o con ivabradina en pacientes con ICA grave tratados con catecolaminas intravenosas. 4. Valorar los efectos de la ivabradina sobre los volúmenes ventriculares en el contexto de la ICA grave por disfunción ventricular izquierda. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients aged ≥ 18 years, with acute heart failure due to left ventricular systolic dysfunction (LVEF ≤ 40%) in sinus rhythm, baseline HR ≥ 90 bpm, with signs of low peripheral perfusion with indication for intravenous inotropic treatment (catecholamines: dobutamine , adrenaline, dopamine or noradrenaline) and admitted to the Cardiological Intensive Care Unit. Pharmacological treatment and stable hemodynamic situation in the 4 hours before inclusion. Pulmonary wedge pressure ≥ 18 mm Hg and systolic blood pressure > 90 mm Hg. Patient's signature on the consent form. |
Pacientes con edad > 18 años, con insuficiencia cardiaca aguda por disfunción sistólica del ventrículo izquierdo (FEVI < 40%) en ritmo sinusal, FC basal > 90 lpm, con signos de baja perfusión periférica con indicación de tratamiento inotrópico intravenoso (catecolaminas: dobutamina, adrenalina, dopamina o noradrenalina) e ingresados en Unidad de Cuidados Intensivos Cardiológicos. Tratamiento farmacológico y situación hemodinámica estable en las 4 horas anteriores a la inclusión. Presión de enclavamiento pulmonar > 18 mm Hg y presión arterial sistólica > 90 mm Hg. Firma de consentimiento informado. |
|
E.4 | Principal exclusion criteria |
Previous treatment with ivabradine (< 48 hours). Known hypersensitivity to Ivabradine. Sickness not corrected by pacemaker. Rhythm different from sinus rhythm. Unstable cardiac rhythm due to paroxysmal atrial fibrillation or atrial flutter, very frequent ventricular or supraventricular extrasystole, ventricular tachycardia, 2nd or 3rd degree AV block. Severe chronic renal failure (FGE ≤15 ml / min) or on chronic treatment with dialysis. QT interval higher than 450 ms. Sepsis as a probable mechanism of tachycardia and hypotension. Need for urgent cardiac surgery, planned within 72 hours of possible inclusion. Severe aortic stenosis or severe valvular disease that requires surgical correction. Severe hepatic insufficiency. Concomitant use of potent CYP3A4 inhibitors. Acute anemia or hypovolemia uncorrected. Pregnancy. |
Tratamiento previo con ivabradina (< 48 horas). Hipersensibilidad conocida a Ivabradina. Enfermedad del seno no corregida por marcapasos. Ritmo diferente al ritmo sinusa.l Ritmo cardiaco inestable por fibrilación auricular o flutter auricular paroxísticos, extrasistolia ventricular o supraventricular muy frecuente, taquicardias ventriculares, bloqueos AV de segundo o 3er grado. Insuficiencia renal crónica grave (FGE < 15 ml/min) o en tratamiento crónico con diálisis. Intervalo QT superior a 450 ms. Sepsis como mecanismo probable de la taquicardia e hipotensión. Necesidad de cirugía cardiaca urgente, prevista en las siguientes 72 horas a la posible inclusión. Estenosis aórtica severa o valvulopatía grave que requiera corrección quirúrgica. Insuficiencia hepática grave. Uso concomitante de inhibidores potentes del CYP3A4. Anemia aguda o hipovolemia no corregidas. Embarazo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of emergent adverse events over 1 month. |
Aparición de acontecimientos adversos emergentes a lo largo de 1 mes. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Analysis of total mortality, mortality due to cardiovascular disease in relation to treatment with ivabradine in patients with severe AHF treated with intravenous catecholamines. Assess the effects of ivabradine on ventricular volumes in the context of severe AHF due to left ventricular dysfunction. |
Análisis de mortalidad total, mortalidad por causa cardiovascular en relación con tratamiento con ivabradina en pacientes con ICA grave tratados con catecolaminas intravenosas. Valorar los efectos de la ivabradina sobre los volúmenes ventriculares en el contexto de la ICA grave por disfunción ventricular izquierda. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.5 | Efficacy | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Tratamiento de cuidado estandar |
Standard of care treatment |
|
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 | 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 |
Ultima visita del sujeto de estudio |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |