| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Heart failure |
| Insuficiencia cardiaca |
|
| E.1.1.1 | Medical condition in easily understood language |
| Heart failure |
| Insuficiencia cardiaca |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
| 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 |
| To determine the effect of TF withdrawal in CRT patients with recovered LVEF, in terms of both image parameters, assessed by changes in LVEF and LV indexed end-systolic volume (VTSVIi) and clinical parameters that translate into worsening of HF. . |
| Determinar el efecto de la retirada del TF en pacientes portadores de TRC con FEVI recuperada, en términos tanto de parámetros de imagen, evaluada mediante cambios en la FEVI y volumen telesistólico indexado del VI (VTSVIi) como de parámetros clínicos que traduzcan empeoramiento de la IC. |
|
| E.2.2 | Secondary objectives of the trial |
1. To determine the safety of TF withdrawal in CRT patients with recovered LVEF, in terms of adverse events during follow-up (total death, cardiovascular death, hospital admission or consultation in the Emergency Department for HF and sustained supraventricular or ventricular arrhythmias)
2. The determination of changes in other echocardiographic measures as well as in the levels of natriuretic peptides, vital signs and scores in the quality of life tests.
3. The influence of cardiomyopathy genotype on the response to medication withdrawal. |
1. Determinar la seguridad de la retirada del TF en pacientes portadores de TRC con FEVI recuperada, en términos de eventos adversos en el seguimiento (muerte total, muete muerte cardiovascular, ingreso hospitalario o consulta en Urgencias por IC y arritmias supraventriculares o ventriculares sostenidas)
2. La determinación de cambios en otras medidas ecocardiogáficas así como en los niveles de péptidos natriuréticos, constantes vitales y puntuaciones en los test de calidad de vida.
3. La influencia de genotipo de la miocardiopatía en la respuesta a la retirada de la medicación. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria:
Patient with a CRT device for at least one year due to the presence of LBBB and LVEF <40% of non-ischemic origin
Current LVEF ≥ 50% and normal volumes in two consecutive echocardiographic studies, separated at least 3 months, and the last one performed in the previous 6 months.
Normally functioning CRT device with stimulation> 95%.
NYHA functional class I-II.
Absence of admissions for HF in the last year.
NT-proBNP <450 pg / ml in sinus rhythm and <900 pg / ml in patients with atrial fibrillation, in the previous 6 months.
Pharmacological treatment with beta-blockers, ACEIs / AIIRA / RNAI with or without MRA.
older than 18 years.
Patients who have given their informed consent in writing. |
Los sujetos deben cumplir todos los siguientes criterios de inclusión:
Paciente portador de un dispositivo de TRC desde al menos un año antes debido a la presencia de BRI y FEVI <40% de origen no isquémico
FEVI actual ≥ 50% y volúmenes normales en dos estudios ecocardiográficos consecutivos, separados al menos 3 meses, y el último realizado en los 6 meses previos.
Dispositivo de TRC normofuncionante con estimulación >95%.
Clase funcional I-II de la NYHA.
Ausencia de ingresos por IC en el último año.
NT-proBNP <450 pg/ml en ritmo sinusal y <900 pg/mL en pacientes en fibrilación auricular, en los 6 meses previos.
Tratamiento farmacológico con betabloqueantes, IECAs/ARAII/ARNI con o sin ARM.
Edad mayor de 18 años.
Pacientes que hayan otorgado su consentimiento informado por escrito. |
|
| E.4 | Principal exclusion criteria |
1. Previous episode of sustained ventricular tachycardia / recovered sudden death / appropriate shock (in the case of a patient with an implantable cardioverter-defibrillator associated with CRT).
2. Uncontrolled arterial hypertension (figures> 140/90 mmHg).
3. Need to use beta-blockers at the medical discretion for other indications such as heart rate (HR) control in atrial fibrillation (in the absence of ablation of the atrioventricular node) or to control other supra or ventricular arrhythmias.
4. Severe valve disease.
5. Diabetic or hypertensive with microalbuminuria or proteinuria.
6. Renal failure with creatinine clearance <30 ml / min / 1.73m2.
7. Fertile women who are neither using contraceptives nor surgically sterilized; pregnant or lactating women.
8. You are currently participating in a clinical trial or have participated in the past 30 days. |
1. Episodio previo de taquicardia ventricular sostenida/muerte súbita recuperada/descarga apropiada (en caso de ser portador de desfibrilador automático implantable asociado a la TRC).
2. Hipertensión arterial no controlada (cifras >140/90 mmHg).
3. Necesidad de uso betabloqueantes a criterio médico por otras indicaciones tales como control de frecuencia cardiaca (FC) en fibrilación auricular (en ausencia ablación del nodo aurículo-ventricular) o para control de otras arritmias supra o ventriculares.
4. Valvulopatía grave.
5. Diabéticos o hipertensos con microalbuminuria o proteinuria.
6. Insuficiencia renal con aclaramiento de creatinina < 30 ml/min/1.73m2.
7. Las mujeres fértiles que no utilizan anticonceptivos ni están esterilizadas quirúrgicamente; las mujeres embarazadas o lactantes.
8. Participa en la actualidad en un ensayo clínico o ha participado durante los últimos 30 días. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Relapse of cardiomyopathy at any time in the study after withdrawal of medication, defined by at least one of the following:
1. A reduction in LVEF of more than 10% (provided that the overall LVEF is <50%).
2. An increase> 15% in the VTSVIi compared to the previous one and in a range higher than the normal value.
3. Clinical evidence of HF based on a global assessment, both clinical and analytical, together with the need to increase the dose of diuretics, as adjudicated by the research team. |
Recaída de la miocardiopatía en cualquier momento del estudio tras la retirada de la medicación, definida por al menos uno de los siguientes:
1. Una reducción de la FEVI de más del 10% (siempre que la FEVI global sea < 50%).
2. Un aumento >15% en el VTSVIi con respecto al previo y en rango superior al valor normal.
3. Evidencia clínica de IC basada en una valoración global tanto clínica como analítica junto a la necesidad de aumentar la dosis de diuréticos, según lo adjudicado por el equipo de investigación. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Combined total mortality, cardiovascular mortality, unplanned hospital admission or emergency room visit for HF and sustained atrial or ventricular arrhythmias (> 30 seconds).
Changes with respect to baseline levels of BP and HR figures
Change from baseline LVEF, left ventricular end-diastolic volume (VTDVIi), body surface indexed left atrium volume (VAIi), and changes from baseline in longitudinal global strain (GLS).
Quantitative changes in NT-proBNP numbers.
Changes from baseline blood pressure and heart rate figures
Changes in the quality of life questionnaires according to The Kansas City Cardiomyopathy Questionnaire (KCCQ) and Minnesota Living With Heart Failure (MLHFQ) scales. |
Combinado de mortalidad total, mortalidad cardiovascular, ingreso hospitalario o visita a Urgencias no planeado por IC y arritmias auriculares o ventriculares sostenidas (>30 segundos).
Cambios con respecto a los niveles basales de cifras de TA y FC
Cambio con respecto a los niveles basales de la FEVI, volumen telediastólico de ventrículo izquierdo (VTDVIi), volumen de aurícula izquierda indexada por superficie corporal (VAIi) y cambios con respecto a los niveles basales en strain global longitudinal (SGL).
Cambios cuantitativos de las cifras de NT-proBNP.
Cambios con respecto a los niveles basales de cifras de tensión arterial y frecuencia cardiaca
Cambios en los cuestionarios de calidad de vida según la escala The Kansas City Cardiomyopathy Questionnaire (KCCQ) y Minnesota Living With Heart Failure (MLHFQ). |
|
| 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 | 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) | 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 | 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 habitual |
| Usual 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 | 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| 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 | 3 |
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