E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atrial fibrillation, stroke, heart failure, myocardial infarction, cognitive dysfunction |
Fibrilación auricular, infarto, insuficiencia cardiaca, infarto agudo de miocardio, disfunción cognitiva |
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E.1.1.1 | Medical condition in easily understood language |
Atrial fibrillation is a common type of cardiac rhythm disorder, which represents an important cause for stroke but also for myocardial infarction and heart muscle weakness (heart failure). |
FA es un tipo común de trastorno del ritmo cardiaco que constituye una causa importante no solo de apoplejía, también de infarto de miocardio y debilidad del músculo cardiaco (insuficiencia cardiaca) |
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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 | 14.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10019280 |
E.1.2 | Term | Heart failures |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061256 |
E.1.2 | Term | Ischaemic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028596 |
E.1.2 | Term | Myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019016 |
E.1.2 | Term | Haemorrhagic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10009841 |
E.1.2 | Term | Cognitive and attention disorders and disturbances |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 test whether an early and comprehensive rhythm control therapy can prevent adverse cardiovascular outcomes in patients with atrial fibrillation (AF) compared to usual care. |
Se investigará si un tratamiento precoz e intensivo de control del ritmo cardiaco puede prevenir complicaciones graves en pacientes con diagnóstico reciente de fibrilación auricular (FA). Dicho tratamiento será comparado con el tratamiento habitual a día de hoy (?usual care?). |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Recent-onset AF (? 1 year prior to enrolment) 2. At least one ECG within recent 12 months that documents AF whereas the AF episode must last longer than 30 s. 3. EITHER one of the following: * age > 75 years or * prior stroke or transient ischemic attack OR two of the following: * age > 65 years, * female sex, * arterial hypertension (chronic treatment for hypertension, estimated need for continuous antihypertensive therapy or resting blood pressure > 145/90 mmHg), * diabetes mellitus (treated by drugs or insulin) or impaired glucose tolerance * severe coronary artery disease (previous myocardial infarction, CABG or PCI) * Stable heart failure (NYHA II or LVEF <50%), * left ventricular hypertrophy on echocardiography (more than 15 mm wall thickness), * chronic kidney disease (MDRD stage III or IV), * peripheral artery disease.
4. Provision of signed informed consent. 5. Age ? 18 years. |
1. FA diagnosticada recientemente (? 1 año antes de la inclusión en el estudio) 2. Presentación de como mín. un EKG con FA documentada de los últimos 12 meses, siempre que el episodio de FA dure al menos 30 segundos 3. AMBOS uno de los continuación: * Paciente mayor de 75 años, * Sexo femenino, * Hipertensión arterial (tratamiento crónico, probable necesidad de un tratamiento continuo o presión arterial en reposo > 145/90 mmHg) * Diabetes mellitus (tratada con medicamentos o insulina) o intolerancia a la glucosa * Enfermedad coronaria grave (historia de IAM, ICP o revascularización quirúrgica) * Insuficiencia cardiaca estable (NYHA estadio II o FEVI < 50 %) * Hipertrofia ventricular izquierda confirmada por ecocardiografía (> 15 mm de grosor de pared) * Enfermedad renal crónica (MDRD estadio III o IV) * Enfermedad vascular periférica.
4. Fecha de firma del paciente 5. El paciente tiene 18 años o más |
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E.4 | Principal exclusion criteria |
1. Any disease that limits life expectancy to less than 1 year. 2. Participation in another clinical trial, either within the past two months or ongoing 3. Previous participation in the EAST trial. 4. Pregnant women or women of childbearing potential not on adequate birth control: only women with a highly effective method of contraception [oral contraception or intra-uterine device (IUD)] or sterile women can be randomized. 5. Breastfeeding women. 6. Drug abuse. 7. Prior AF ablation or surgical therapy of AF. 8. Previous therapy failure on amiodarone, e.g. patients who suffered from symptomatic recurrent AF that required escalation of therapy while on amiodarone. 9. Patients not suitable for rhythm control of AF. 10. Severe mitral valve stenosis. 11. Prosthetic mitral valve. 12. Clinically relevant hepatic dysfunction requiring specific therapy. 13. Clinically manifest thyroid dysfunction requiring therapy. After successful treatment of thyroid dysfunction, patients may be enrolled when their thyroid function is controlled. 14. Severe renal dysfunction (stage V, requiring or almost requiring dialysis). |
1. Cualquier enfermedad con una esperanza de vida inferior a 1 año 2. Participaciones anteriores (en los últimos dos meses) o actuales en otro estudio clínico. 3. Participación anterior en el estudio EAST 4. Mujeres embarazadas o en edad de procrear sin contracepción adecuada: solo mujeres que tomen anticopceptivos fiables (píldora anticonceptiva o DIU) o mujeres estériles pueden ser aleatorizadas 5. Mujeres lactantes 6. Abuso de medicamentos 7. Ablación de FA previa 8. Fracaso del tratamiento previo con amiodarona (v.g. pacientes con recidiva de FA sintomática durante tratamiento con amiodarona, que requieran un tratamiento más potente 9. Pacientes no aptos para un tratamiento de control de ritmo de FA. 10. Estenosis grave de la válvula mitral 11. Prótesis mitral 12. Disfunción hepática clinicamente relevante que necesita una terapia específica 13. Disfunción tiroidea clínicamente manifiesta y que necesita tratamiento. Tras el tratamiento con éxito de una disfunción tiroidea, un paciente puede ser aleatorizado. 14. Disfunción renal grave (estadio V, necesidad o necesidad próxima de diálisis) |
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E.5 End points |
E.5.1 | Primary end point(s) |
A composite of cardiovascular death, stroke, transitoric ischemic attack (TIA), and hospitalization due to worsening of heart failure or due to acute coronary syndrome. The first co-primary outcome parameter is defined as the time to the first occurrence of a composite of cardiovascular death, stroke / transient ischemic attack (TIA), and hospitalization due to worsening of heart failure or due to acute coronary. The second co-primary outcome parameter is nights spent in hospital per year. |
Una combinación de muerte cardiovascular, accidente cerebrovascular (ACVA), ataque isquémico transitorio (AIT) y la hospitalización debido al empeoramiento de la insuficiencia cardiaca o a un síndrome coronario agudo. El primer parámetro del resultado coprimario está definido como el tiempo en el que aparece la primera combinación de muerte cardiovascular , accidente cerebrovascular (ACVA) / ataque isquémico transitorio (AIT) y la hospitalización debido al empeoramiento de la insuficiencia cardiaca o a un síndrome coronario agudo. El segundo parámetro del resultado coprimario está definido por el número de noches hospitalizado por año. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
A first interim analysis is to be performed when the first 171 events in the 1st co-primary outcome have been observed. If the assumptions are met, this will happen 32 months after the first patient was randomized. The second interim analysis is to be performed when the first 343 events in the 1st co-primary outcome have been observed (approximately 47 months after the first patient was randomized). The third interim analysis is to be performed when the first 514 events have been observed (approximately 59 (11) months after the first (last) patient was randomized). The final analysis is to be performed when 685 events have been observed. If the assumptions are met, this will happen 72 (24) months after the first (last) patient was randomized. |
El primer análisis interino se efectuará cuando se hayan observado los primeros 171 sucesos en el primer resultado coprimario. Si se cumplen las previsiones, esto tendrá lugar 32 meses tras la aleatorización del primer paciente. El segundo análisis interino se efectuará cuando se hayan observado los primeros 343 sucesos en el primer resultado coprimario (aprox. 47 meses después de la aleatorización del primer paciente). El tercer análisis interino se efectuará cuando se hayan observado los primeros 514 sucesos (aprox. 59 (11) meses después de la aleatorización del primer (último) paciente). El análisis final se efectuará cuando se hayan observado 685 sucesos. Si se cumplen las previsiones, esto tendrá lugar 72 (24) meses después de la aleatorización del primer (último) paciente). |
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E.5.2 | Secondary end point(s) |
1. Cardiovascular death 2. stroke 3. worsening of heart failure assessed by hospitalizations 4. acute coronary syndrome assessed by hospitalizations 5. time to recurrent atrial fibrillation 6. cardiovascular hospitalisations 7. all-cause hospitalisations 8. left ventricular function assessed by transthoracic echocardiography 9. quality of life changes assessed by EQ-5D and SF-12 10. cognitive function assessed by MoCA |
1. Muerte cardiovascular 2. Infarto 3. empeoramiento de la insuficiencia cardiaca evaluada por las hospitalizaciones 4. síndrome coronario agudo evaluado por las hospitalizaciones 5. tiempo de fibrilación auricular recurrente 6. hospitalizaciones cardiovasculares 7. todas las causas de hospitalizaciones 8. función ventricular izquierda evaluada por la ecocardiografía transtorácica 9. calidad de los cambios de vida evaluados por EQ-5D y SF-12 10. función cognitiva evaluada por MoCA |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation of secondary end points no. 1-7 at the end of the trial (i.e. after 6 years). Evaluation of secondary end points no. 8-10 at month 24 after randomisation. |
Evaluación de los puntos finales secundarios nº 1-7 en el final del ensayo (p.ej. después de 6 años). Evaluación de los puntos finales secundarios nº 8-10 en el mes 10 después de la aleatorización. |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
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 |
tratamiento habitual definido por las directrices actuales ESC e incluyendo el tratamiento de contro |
usual care as defined by the current ESC guidelines and including delayed rhythm control therapy |
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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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 190 |
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 |
Belgium |
Czech Republic |
Denmark |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
Switzerland |
United Kingdom |
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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
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EAST is an event-driven trial. The final analysis will be performed if 685 events in the 1st co-primary outcome have been observed. If the statistical assumptions are met, this will happen 6 years after the first patient has been randomised in the study. Thus a duration of the entire trial of around 6 years is expected. All patients will be followed-up until the end of the trial. |
EAST es un ensayo de seguimiento de sucesos. El análisis final se realizará si se han observado 685 sucesos en el primer resultado co-primario. Si se cumplen los supuestos estadísticos, esto ocurrirá 6 años después de la aleatorización del primer paciente. Por consiguiente, se espera que el ensayo completo tenga una duración aproximada de 6 años. A todos los pacientes se les hará un seguimiento hasta el final del ensayo. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |