E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart Failure with reduced ejection fraction (HFrEF) |
Insuficiencia cardíaca con fracción de eyección reducida (ICFEr) |
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E.1.1.1 | Medical condition in easily understood language |
Heart failure |
Insuficiencia cardíaca |
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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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | 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 |
To assess changes in daily non-sedentary daytime activity between baseline and after 12 weeks of treatment in sacubitril/valsartan vs. enalapril treated patients. |
Evaluar los cambios en la actividad no sedentaria diurna diaria desde la basal y hasta la semana 12 de tratamiento en pacientes tratados con sacubitril/valsartán vs. enalapril. |
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E.2.2 | Secondary objectives of the trial |
- To compare the effects of sacubitril/valsartan vs. enalapril on patients’ symptom progression by means of the Patient Global Assessment (PGA) questionnaire - To assess dynamics of changes from baseline in daily non-sedentary daytime physical activity in sacubitril/valsartan vs. enalapril treated patients in weekly and two-weekly intervals. - To assess changes from baseline in mean daily non-sedentary daytime physical activity classified by its intensity for sacubitril/valsartan vs. enalapril treated patients - To assess the difference in non-sedentary daytime physical activity between sacubitril/valsartan vs. enalapril treated patients during the treatment period - To assess changes on M6min (an actigraphy-based measure of the peak six minutes of daytime physical activity) in sacubitril/valsartan vs. enalapril treated patients - To assess changes from baseline in exercise capacity assessed by means of the 6-minute walking test |
-Comparar efectos de sacubitril/valsartán vs enalapril en la progresión sintomática de los pacientes mediante cuestionario PGA -Evaluar dinámica de los cambios respecto a la basal en la actividad física no sedentaria diurna diaria en pacientes tratados con sacubitril/valsartán vs enalapril en intervalos de 1 y 2 semanas -Evaluar cambios respecto a la basal en la media de la actividad física no sedentaria diurna diaria clasificada por su intensidad en pacientes tratados con sacubitril/valsartán vs enalapril -Evaluar la diferencia en la actividad física no sedentaria diurna entre pacientes tratados con sacubitril/valsartán vs enalapril durante periodo de tratamiento -Evaluar cambios respecto a la basal en M6min (una medida mediante actigrafía del máximo de actividad física diurna en seis minutos) en pacientes tratados con sacubitril/valsartán vs enalapril -Evaluar cambios respecto a la basal en la capacidad de ejercicio evaluada mediante prueba marcha de 6min |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written informed consent obtained before any study assessment is performed. - Ambulatory ≥ 18 years of age with a diagnosis of chronic symptomatic HF (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 40% AND one of the following two criteria: - Plasma NT-proBNP level of ≥ 300 pg/mL or BNP ≥ 100 pg/mL (measurement may be recorded no longer than past 12 months) OR - Confirmation of a heart failure hospitalization last 12 months. - Patients must be on stable HF medication for at least 4 weeks prior to Week - 2, where the minimal daily dose of current evidence based therapies is equivalent to at least 2.5 mg/d enalapril - Willingness to wear the accelerometer wristband continuously for the duration of the trial. - Patients must be living in a setting, allowing them to move about freely and where they are primarily self responsible for scheduling their sleep and daily activities. |
- El consentimiento informado por escrito se debe obtener antes de realizar cualquier evaluación del estudio. - Pacientes ambulatorios >= 18 años de edad con un diagnóstico de IC sintomática crónica (clase >= II de la NYHA) con fracción de eyección reducida, definida como FEVI ≤ 40 % Y uno de los dos criterios siguientes: - nivel de NT-proBNP en plasma >= 300 pg/ml o BNP >= 100 pg/ml (la medición debe registrarse como máximo en los últimos 12 meses) O - confirmación de una hospitalización por insuficiencia cardíaca en los últimos 12 meses.
- Los pacientes deben estar recibiendo una medicación estable para la IC durante al menos las 4 semanas anteriores a la semana -2; donde la dosis diaria mínima de IECA/ARAII equivale al menos a 2,5 mg/día de enalapril
- Voluntad de llevar siempre puesto el acelerómetro de muñeca durante todo el ensayo.
- Los pacientes deben vivir en un entorno que les permita moverse libremente y donde asuman su propia responsabilidad para programar su sueño y sus actividades diarias |
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E.4 | Principal exclusion criteria |
- History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes - Use of sacubitril/valsartan prior to week - 2. - Bedridden patients, or patients with significantly impaired/limited physical activity and/or fatigue due to medical conditions other than HF, such as, but not limited to angina (chest pain at exertion), arthritis, gout, peripheral artery occlusive disease, obstructive or restrictive lung disease, malignant disease, neurological disorders (e.g. Parkinson’s or Alzheimer’s disease, central and peripheral neuroinflammatory and degenerative disorders or functional central nervous lesions due to hemodynamic or traumatic incidents), injuries (incl. diabetic foot ulcers) or missing limbs - Patients with palsy, tremor or rigor affecting the nondominant arm. - Patients with any skin or other condition of the nondominant arm that would limit the ability to wear the actigraphy device continuously (24h/day) over 14 weeks. - Patients fully depending on a mobility support system, e.g. wheelchair, scooter or walker. Patients are allowed to use a cane as long as this is not used with the non- dominant arm. |
- Antecedentes de hipersensibilidad a alguno de los fármacos del estudio o sus excipientes o a fármacos de clases químicas similares. - Uso de sacubitril/valsartán antes de la visita 1. - Pacientes postrados en la cama o pacientes con limitación/deterioro significativo de la actividad física o fatiga debido a otras enfermedades, salvo IC, como angina (dolor en el pecho con esfuerzo), artritis, gota, arteriopatía oclusiva periférica, enfermedad pulmonar obstructiva o restrictiva, enfermedad maligna, trastornos neurológicos (p. ej., enfermedad de Parkinson o Alzheimer, trastornos neuroinflamatorios centrales y periféricos y trastornos degenerativos o lesiones funcionales en el sistema nervioso central por incidentes hemodinámicos o traumáticos), lesiones (incl. úlceras de pie diabético) o pérdida de alguna extremidad, entre otras enfermedades. - Pacientes con parálisis, temblores o rigidez que afecten al brazo no dominante. - Pacientes con cualquier enfermedad cutánea o de otro tipo en el brazo no dominante que limitara la capacidad de llevar siempre puesto el actígrafo (24 horas al día) durante 14 semanas. - Pacientes que dependan plenamente de un sistema de soporte para la movilidad, p. ej., silla de ruedas, scooter o andador. Los pacientes pueden utilizar un bastón siempre que no se utilice con el brazo no dominante. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in mean daily non-sedentary daytime activity between baseline and end of study |
Cambio respecto a la basal en la media de la actividad diurna diaria no sedentaria, entre la basal y el final del estudio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline (week -2 to Week 0), last 14 days of treatment (week 10 to week 12) |
Basal (de semana -2 a semana 0), ultimos 14 dias de tratamiento (de semana 10 a semana 12) |
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E.5.2 | Secondary end point(s) |
1) Percentage of patients with improved symptoms of heart failure as assessed by patient's Global Assessment 2) Change from baseline in mean daily non sedentary daytime activity in weekly and two-weekly intervals 3) Change from baseline in mean daily nonsedentary daytime physical activity classified by its intensity 4) Total weekly time spent in nonsedentary daytime physical activity 5) Total weekly time spent in light nonsedentary daytime physical activity 6) Total weekly time spent in moderate-tovigorous nonsedentary daytime physical activity 7) Change from baseline in peak six minutes of daytime physical activity 8) Change from baseline in means of 6-minute walking test 9) Percentage of patients who show increased levels of nonsedentary daytime |
1) Porcentaje de pacientes con una mejoría de los síntomas de IC según la PGA. 2) cambio respecto a la basal en la media de la actividad no sedentaria diurna diaria en intervalos de una y dos semanas. 3) cambio respecto a la basal en la media de la actividad fisica no sedentaria diurnal clasificada por su intensidad. 4) tiempo total por semana dedicado a realizar una actividad física no sedentaria diurna. 5) tiempo total por semana dedicado a realizar una actividad física diurnal no sedentaria ligera 6) tiempo total por semana dedicado a realizar una actividad física diurnal no sedentaria de moderada a intensa 7) cambio respecto a la basal en el pico de 6 minutos de la actividad fisica diaria 8) cambio respecto a la basal en la prueba de marcha de 6 minutos 9) Porcenjate de pacientes que muestran un aumento en los niveles de no sedentarismo diario |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 4, Week 8, Week 12 2) Week - 1 to Week 0, Week - 2 to Week 0, from week 0 to Week 12 3) Baseline (week - 2 to week 0), week 2 to week 4, week 6 to week 8, week 10 to week 12 4) week 0 to week 12 in weekly intervals 5)week 0 to week 12 in weekly intervals 6) week 0 to week 12 in weekly intervals 7) week -2 to week 0, week 2 to week 4, week 6 to week 8, week 10 to week 12 8) week 0, week 4, week 8, week 12 9) Baseline (week -2 to week 0), Week 12 |
1) Semana 4, semana 8, semana 12 2) De semana - 1 a semana 0, de semana - 2 a semana 0, de semana 0 a semana 12 3) Basal (de semana - 2 a semana 0), de semana 2 a semana 4, de semana 6 a semana 8, de semana 10 a semana 12 4) de semana 0 a semana 12 en intervalos semanales 5) de semana 0 a semana 12 en intervalos semanales 6) de semana 0 a semana 12 en intervalos semanales 7) de semana -2 a semana 0, de semana 2 a semana 4, de semana 6 a semana 8, de semana 10 a semana 12 8) semana 0, semana 4, semana 8, semana 12 9) Baseline (de semana-2 a semana 0), semana 12 |
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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 | No |
E.6.4 | Safety | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
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) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 22 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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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LVLS |
Ultima Visita Ultimo Sujeot |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |