E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart Failure with reduced ejection fraction (HF-rEF) stabilized after hospitalization due to acute decompensated heart failure episode. |
Insuficiencia cardíaca con fracción de eyección reducida (HF-rEF) estabilizada después de la hospitalización tras un episodio de descompensación aguda. |
|
E.1.1.1 | Medical condition in easily understood language |
Heart Failure |
Insuficiencia cardíaca |
|
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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
|
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 primary objective of this study is to evaluate the proportion of patients in the Pre- and Post-discharge treatment initiation groups achieving the target dose of 200 mg LCZ696 twice daily at the end of the week-10 after randomization (Treatment Epoch), regardless of previous temporary dose interruption or down-titration. |
El objetivo principal de este estudio es evaluar la proporción de pacientes en los grupos de inicio del tratamiento antes del alta y después del alta que alcancen la dosis objetivo de 200 mg de LCZ696 dos veces al día al final de la semana 10 después de la aleatorización (Etapa de tratamiento), independientemente de la interrupción temporal previa de la dosis o del ajuste descendente previo de la dosis. |
|
E.2.2 | Secondary objectives of the trial |
- To assess the proportion of patients that, regardless of previous dose interruption or downtitration during the Treatment Epoch, achieved and maintained either the dose of 100 mg and/or 200 mg LCZ696 bid. - To asssess the proportion of patients that, regardless of previous dose interruption or downtitration during the Treatment Epoch, achieved and maintained any dose of LCZ696. - To assess the proportion of patients permanently discontinued from study drug, due to Adverse Events during the 10-week Treatment Epoch. |
- Evaluar la proporción de pacientes que, independientemente de la interrupción o ajuste descendente previo de la dosis durante la Etapa de tratamiento, alcanzaron y mantuvieron la dosis de 100 mg y/o 200 mg de LCZ696 bid. - Evaluar la proporción de pacientes que, independientemente de la interrupción o ajuste descendente previo de la dosis durante la Etapa de tratamiento, alcanzaron y mantuvieron cualquier dosis de LCZ696. - Evaluar la proporción de pacientes a quienes se les retiró permanentemente la medicación del estudio, debido a acontecimientos adversos, durante la Etapa de tratamiento de 10 semanas. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients hospitalized due to acute decompensated HF episode (ADHF) - Diagnosis of HF New York Heart Association class II-to-IV and reduced ejection fraction - Patients did not receive any IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for ADHF to randomization - Stabilized (while in the hospital) for at least 24 hours leading to randomization - Other protocol-defined inclusion criteria may apply. |
- Pacientes hospitalizados debido a un episodio de descompensación aguda de la insuficiencia cardiaca (ADHF) - Diagnóstico de IC clase II a IV de la New York Heart Association y fracción de eyección reducida - Pacientes que no hayan recibido ningún vasodilatador i.v. (excepto nitratos), y/o ninguna terapia inotrópica i.v. desde el momento de la presentación debido a ADHF hasta la Aleatorización - Estabilizado (mientras está en el hospital) durante al menos 24 horas hasta la Aleatorización - Se pueden aplicar otros criterios de inclusión definidos en el protocolo. |
|
E.4 | Principal exclusion criteria |
- Symptomatic hypotension and/or a SBP < 110 mm Hg or SBP > 180 mm Hg prior to randomization - End stage renal disease at screening; or estimated GFR < 30 mL/min/1.73 m2 as measured by (MDRD) formula at randomization. - Serum potassium > 5.4 mmol/L at randomization. - Current hospitalization where patient does not receive treatment for decompensated HF. - Known history of hereditary or idiopathic angioedema or angioedema related to previous ACE inhibitor or ARB therapy - Severe hepatic impairment, biliary cirrhosis and cholestasis - Other protocol-defined exclusion criteria may apply. |
- Hipotensión sintomática y/o PAS < 110 mmHg o PAS > 180 mmHg antes de la aleatorización - Enfermedad renal en fase terminal en la Selección; o TFG estimada < 30 mL/min/1,73 m2 medida mediante la fórmula de la modificación simplificada de la dieta en la enfermedad renal (MDRD) en la aleatorización. - Potasio sérico > 5,4 mmol/L en la aleatorización. - Antecedentes conocidos de angioedema hereditario o idiopático o angioedema relacionado con terapia previa con IECA o ARAII - Insuficiencia hepática grave, cirrosis biliar y colestasis - Se pueden aplicar otros criterios de exclusión definidos en el protocolo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients who achieve 10 weeks up-titration success |
La proporción de pacientes que alcancen 10 semanas de ajuste ascendente |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
10 weeks after randomization |
10 semanas después de la aleatorización |
|
E.5.2 | Secondary end point(s) |
- Assess the proportion of patients achieving and maintaining either the dose of 100 mg and/or 200 mg LCZ696 bid for at least 2 weeks leading to week 10 after randomization. - Assess the proportion of patients achieving and maintaining any dose of LCZ696 for at least 2 weeks leading to week 10 after randomization. - Assess the proportion of patients permanently discontinuation from study drug, at any time between randomization and week 10. |
- Evaluar la proporción de pacientes que alcanzaron y mantuvieron o bien la dosis de 100 mg y/o 200 mg de LCZ696 bid durante al menos 2 semanas lo que lleva a la semana 10 después de la aleatorización. - Evaluar la proporción de pacientes que alcanzaron y mantuvieron cualquier dosis de LCZ696 durante al menos 2 semanas hasta llegar a la semana 10 después de la aleatorización. - Evaluar la proporción de pacientes a quienes se les haya retirado permanentemente la medicación del estudio, en cualquier momento entre la aleatorización y la semana 10. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
10 weeks after randomization |
10 semanas después de la aleatorización |
|
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 |
Pre-discharge initiation of LCZ696 arm versus the Post-discharge initiation of LCZ696 arm |
|
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 155 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Canada |
Czech Republic |
Finland |
France |
Germany |
Hungary |
Italy |
Lebanon |
Mexico |
Norway |
Poland |
Portugal |
Russian Federation |
Saudi Arabia |
Slovakia |
Spain |
Sweden |
Switzerland |
Turkey |
United Arab Emirates |
United Kingdom |
|
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
|
Expected LVLS: 27-Feb-2018 |
Ultima visita del ultimo paciente esperada: 27-feb-2018 |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |