| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with atherothrombotic cardiovascular disease |
| Pacientes con enfermedad cardiovascular aterotrombótica |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with atherothrombotic cardiovascular disease |
| Pacientes con enfermedad cardiovascular aterotrombótica |
|
| 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 | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10007648 |
| E.1.2 | Term | Cardiovascular disease, unspecified |
| 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 |
| To determine whether the treatment with a new therapeutic strategy (the Fuster-CNIC-Ferrer cardiovascular polypill) is non-inferior to usual care in terms of low-density lipoprotein cholesterol (LDLc) and blood pressure reductions in subjects with atherothrombotic cardiovascular disease after 6 months of follow-up |
| Determinar si el tratamiento con una nueva estrategia terapéutica (polipíldora cardiovascular de Fuster-CNIC-Ferrer) no es inferior al tratamiento habitual en la reducción del colesterol de lipoproteína de baja densidad (cLDL) y la presión arterial en sujetos con enfermedad cardiovascular aterotrombótica después de 6 meses de seguimiento. |
|
| E.2.2 | Secondary objectives of the trial |
§ To assess whether the treatment with the cardiovascular polypill is non-inferior to usual care in terms of LDLc and blood pressure reductions according to coronary artery disease, stroke and peripheral artery disease of patients.
§ To evaluate the percentage of patients with LDLc and blood pressure under control according to 2016 European Guidelines on cardiovascular disease prevention.
§ To determine changes in total cholesterol, LDLc, high-density lipoprotein cholesterol (HDLc), non-HDLc, triglycerides and blood pressure after 6 months of follow-up.
§ To evaluate satisfaction with medication and patients' preferences in preventive treatment of secondary cardiovascular events with a cardiovascular polypill.
§ To evaluate the safety of the cardiovascular polypill. |
§ Evaluar si el tratamiento con la polipíldora cardiovascular no es inferior al tratamiento habitual en términos de LDLc y la reducción de la presión arterial según la enfermedad arterial coronaria, el accidente cerebrovascular y la enfermedad arterial periférica de los pacientes.
§ Evaluar el porcentaje de pacientes con LDLc y presión arterial bajo control de acuerdo con las Directrices europeas de 2016 sobre prevención de enfermedades cardiovasculares.
§ Determinar los cambios en el colesterol total, LDLc, colesterol de lipoproteínas de alta densidad (HDLc), colesterol no HDL, triglicéridos y presión arterial después de 6 meses de seguimiento.
§ Evaluar la satisfacción con la medicación y las preferencias de los pacientes en el tratamiento preventivo de eventos cardiovasculares secundarios con una polipíldora cardiovascular.
§ Evaluar la seguridad de la polipíldora cardiovascular. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
§ Age ≥18 and <80 years old; both genders.
§ Subjects with atherothrombotic cardiovascular disease, with at least one of the following clinical events:
Previous acute myocardial infarction (>12 months after the event).
Cardiac revascularization with coronary stent (>12 months after the surgery) or coronary artery bypass grafting (3 months after the surgery).
Diagnosis of stable angina (patients to be submitted to a coronary interventional procedure or functional (ischemic test) and/or anatomic (coronary stenosis assessed by coronary angiography or computed tomography).
Previous ischemic stroke with atherothrombotic background, including lacunar infarction (>12 months after the event).
Peripheral artery disease, including patients with stable claudication (>6 months) or operated patients (revascularization or amputation) (2 weeks after the surgery).
§ Subjects treated with an ACE inhibitor or ARB, statin and acetylsalicylic acid for secondary cardiovascular prevention.
§ Subjects who are clinically stable, with no changes in medication for LDLc and blood pressure control within the last 3 months, and in whom it is not planned to change their medication for LDLc and blood pressure in the following 6 months after randomisation.
§ Written informed consent form. |
§ Edad ≥18 y <80 años; ambos géneros.
§ Sujetos con enfermedad cardiovascular aterotrombótica, con al menos uno de los siguientes eventos clínicos:
Infarto agudo de miocardio previo (> 12 meses después del evento).
Re Revascularización cardíaca con stent coronario (> 12 meses después de la cirugía) o injerto de derivación de la arteria coronaria (3 meses después de la cirugía).
Diagnóstico de angina estable (pacientes que se someterán a un procedimiento de intervención coronaria o funcional (prueba de isquemia) y / o anatómica (estenosis coronaria evaluada mediante angiografía coronaria o tomografía computarizada).
Accidente cerebrovascular isquémico previo con antecedentes aterotrombóticos, incluido infarto lacunar (> 12 meses después del evento).
Enfermedad de la arteria periférica, incluidos pacientes con claudicación estable (> 6 meses) o pacientes operados (revascularización o amputación) (2 semanas después de la cirugía).
§ Sujetos tratados con un inhibidor de la ECA o BRA, estatinas y ácido acetilsalicílico para la prevención cardiovascular secundaria.
§ Sujetos que son clínicamente estables, sin cambios en la medicación para el LDLc y el control de la presión arterial en los últimos 3 meses, y en quienes no está previsto cambiar su medicación por LDLc y presión arterial en los 6 meses posteriores a la aleatorización.
§ Formulario de consentimiento informado por escrito. |
|
| E.4 | Principal exclusion criteria |
§ Any contraindication to the polypill, such as:
Patients on haemodialysis or with severe renal impairment (defined by creatinine clearance <30 ml/min).
Patients with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation >3 times the upper limit of normal (ULN) or with severe or active hepatic impairment.
Patients with hypersensitivity to any of the components of the polypill (atorvastatin, ramipril or acetylsalicylic acid), soy, peanuts, or to any ACE inhibitors or salicylates other than acetylsalicylic acid or ramipril.
Patients with a history of asthma episodes or nasal polyps associated with asthma, or other allergic reactions due to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
Patients with active recurrent peptic ulcer, history and/or active gastric or intestinal bleeding, cerebrovascular haemorrhage, or regular history of dyspepsia.
Patients with anaemia (haemoglobin <10 g/dl) or worsening of haemoglobin in the 3 months prior to the study, suggesting the presence of active bleeding which may contraindicate the use of acetylsalicylic acid.
Patients with haemophilia or other disorders of coagulation.
Patients with myopathy, myalgia, myositis or a history of rhabdomyolysis, or creatine kinase levels >5 ULN (it is recommended not to measure the creatine kinase level after intense exercise).
Patients with a history of angioedema or cough due to ACE inhibitors.
Patients with bilateral renal artery stenosis or renal artery stenosis with a single functioning kidney.
§ Patients in whom, at the discretion of the investigator, it is not clinically appropriate to use the polypill (including atorvastatin 20 or 40 mg and ramipril 2.5 to 10 mg) as treatment for the control of LDLc cholesterol and blood pressure.
§ Subjects with suspected familiar hypercholesterolemia or triglycerides >400 mg/dl.
§ Subjects with diagnosed of congestive heart failure (New York Heart Association [NYHA] class III-IV).
§ Patients diagnosed with atrial fibrillation.
§ Patients with haemorrhagic stroke, cardioembolic stroke or stroke of undetermined aetiology.
§ Women who are pregnant, breastfeeding or planning to become pregnant during the study, as well as fertile women who do not take adequate contraceptive measures such as: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence). In fertile women, additional pregnancy tests should be performed at monthly intervals.
§ Presence of major systemic illnesses that in the investigator’s opinion may interfere with the study procedures and/or assessments.
§ Patients with a mental illness (such as dementia) or living in a nursing home or committed to an institution by an order issued by the judicial or the administrative authorities that may limit their capacity of self-care.
§ Medical history of drug/alcohol abuse.
§ Participants in another clinical trial.
§ Patients treated with the polypill prior to randomisation.
§ Patients with active cancer or with chemotherapy treatment. |
§ Cualquier contraindicación para la polipíldora, como:
Pacientes en hemodiálisis o con insuficiencia renal grave (definida por el aclaramiento de creatinina <30 ml / min).
Pacientes con elevación de alanina aminotransferasa (ALT) o aspartato aminotransferasa (AST)> 3 veces el límite superior de la normalidad (LSN) o con insuficiencia hepática grave o activa.
Pacientes con hipersensibilidad a cualquiera de los componentes de la polipíldora (atorvastatina, ramipril o ácido acetilsalicílico), soja, maní o cualquier otro inhibidor de la ECA o salicilato que no sea ácido acetilsalicílico o ramipril.
Pacientes con antecedentes de episodios de asma o pólipos nasales asociados con asma u otras reacciones alérgicas debidas al ácido acetilsalicílico u otros medicamentos antiinflamatorios no esteroideos.
Pacientes con úlcera péptica recurrente activa, antecedentes y / o hemorragia gástrica o intestinal activa, hemorragia cerebrovascular o antecedentes de dispepsia.
Pacientes con anemia (hemoglobina <10 g / dl) o empeoramiento de la hemoglobina en los 3 meses anteriores al estudio, lo que sugiere la presencia de sangrado activo que puede contraindicar el uso de ácido acetilsalicílico.
Pacientes con hemofilia u otros trastornos de la coagulación.
Pacientes con miopatía, mialgia, miositis o antecedentes de rabdomiolisis o niveles de creatina quinasa> 5 ULN (se recomienda no medir el nivel de creatina quinasa después del ejercicio intenso).
Pacientes con antecedentes de angioedema o tos debido a inhibidores de la ECA.
Pacientes con estenosis bilateral de la arteria renal o estenosis de la arteria renal con un solo riñón funcional.
§ Pacientes en los que, según el criterio del investigador, no sea clínicamente apropiado usar la polipíldora (que incluye atorvastatina 20 o 40 mg y ramipril de 2,5 a 10 mg) como tratamiento para el control del colesterol LDL y la presión arterial.
§ Sujetos con sospecha de hipercolesterolemia familiar o triglicéridos> 400 mg / dl.
§ Sujetos con diagnóstico de insuficiencia cardíaca congestiva (New York Heart Association [NYHA] clase III-IV).
§ Pacientes diagnosticados con fibrilación auricular.
§ Pacientes con accidente cerebrovascular hemorrágico, accidente cerebrovascular cardioembólico o accidente cerebrovascular de etiología indeterminada.
§ Mujeres que están embarazadas, amamantando o que planean quedar embarazadas durante el estudio, así como mujeres fértiles que no toman medidas anticonceptivas adecuadas, como: anticoncepción combinada (estrógeno y progestágeno) asociada con la inhibición de la ovulación (oral, intravaginal o transdermal), anticoncepción hormonal con progestágeno solo asociada con la inhibición de la ovulación (oral, inyectable o implantable), dispositivo intrauterino, sistema de liberación de hormonas intrauterinas, oclusión tubárica bilateral, pareja vasectomizada o abstinencia sexual). En mujeres fértiles, se deben realizar pruebas de embarazo adicionales a intervalos mensuales.
§ Presencia de enfermedades sistémicas importantes que, en opinión del investigador, pueden interferir con los procedimientos y / o evaluaciones del estudio.
§ Pacientes con una enfermedad mental (como la demencia) o que viven en un hogar de convalecencia o que han sido asignados a una institución mediante una orden emitida por la autoridad judicial o administrativa que puede limitar su capacidad de autocuidado.
§ Antecedentes médicos de abuso de drogas / alcohol.
§ Participantes en otro ensayo clínico.
§ Pacientes tratados con la polipíldora antes de la asignación al azar.
§ Pacientes con cáncer activo o con tratamiento de quimioterapia. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Systolic blood pressure and LDLc |
| Presión arterial sistólica y cLDL |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At the end of the study treatment period. |
| Al final del periodo de tratamiento del estudio. |
|
| E.5.2 | Secondary end point(s) |
§ Systolic blood pressure and LDLc levels in subgroups of patients with atherothrombotic cardiovascular disease with coronary artery disease, stroke and/or peripheral artery disease.
§ The percentage of patients with LDLc and blood pressure under control as per the 2016 European Guidelines on Cardiovascular Disease Prevention
§ Changes in systolic/diastolic blood pressure and total cholesterol, LDLc, HDLc, non-HDLc and triglyceride levels
§ The change in patients’ satisfaction with medication according to the abbreviated Treatment Satisfaction Questionnaire for Medication19
§ The safety of the polypill |
§ Presión arterial sistólica y niveles de LDLc en subgrupos de pacientes con enfermedad cardiovascular aterotrombótica con arteriopatía coronaria, accidente cerebrovascular y / o enfermedad arterial periférica.
§ El porcentaje de pacientes con LDLc y presión arterial bajo control según las Guías Europeas 2016 sobre Prevención de Enfermedades Cardiovasculares
§ Cambios en la presión arterial sistólica / diastólica y colesterol total, LDLc, HDLc, niveles sin HDLc y triglicéridos
§ El cambio en la satisfacción de los pacientes con la medicación de acuerdo con el Cuestionario de Satisfacción de Tratamiento abreviado para Medicación19.
§ La seguridad de la polipíldora |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| At month 6 and throughout the study. |
| Al mes 6 y durante el estudio. |
|
| 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 | 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) | 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 | 32 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 70 |
| 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 |
| Ireland |
| Italy |
| Mexico |
| Portugal |
| Spain |
|
| 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
|
| Folow up visit 28 days after the end of treatment visit |
| Visita de de seguimiento 28 días después del final de tratamiento |
|
| 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 | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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