E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute coronary syndrome |
Sindrome coronario agudo |
|
E.1.1.1 | Medical condition in easily understood language |
Acute coronary syndrome |
Sindrome coronario agudo |
|
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 |
Efficacy of ticagrelor, at steady state, to improve endothelial function as compared to clopidogrel or prasugrel. |
Eficacia de ticagrelor en fase estable, para mejorar la función endotelial comparado con clopidogrel o prasugrel. |
|
E.2.2 | Secondary objectives of the trial |
?To asses ischemic and bleeding parameters ?To assess if treatment with ticagrelor, both acutely and at steady state is associated to an improved endothelial function phenotype as compared to clopidogrel or prasugrel and its relationship with on-treatment residual P2Y12 reactivity and aspirin reaction units, ADMA and other markers of endothelial function, as well as adenosine plasma concentration (APC). ?Overall tolerability cable |
?Evaluar parámetros isquémicos y hemorrágicos ?Evaluar si el tratamiento con ticagrelor en situación de tratamiento inicial o estable, se asocia a una mejora en el fenotipo de la función endotelial, comparado con clopidogrel o prasugrel; su relación con la reactividad P2Y12 residual durante el tratamiento, y unidades de reacción a aspirina, ADMA y otros marcadores de la función endotelial, así como la concentración de adenosina plasmática (APC). ?Tolerancia general |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a.Patients will be males or females at least 18 years of age. b.Patients who experienced an ACS (including STEMI or NSTEMI) at least 30 days before, c.Ongoing treatment for at least 30 days with dual anti-platelet therapy consisting of aspirin, at doses of 75-160 mg daily and one commercially available P2Y12 oral inhibitor: ticagrelor, clopidogrel or prasugrel at on-label maintenance regimen. d.Free from bleeding (defined as BARC type 2 or greater) or ischemic recurrences. e.Patients who have signed informed consent to participate in the study. |
a.Pacientes hombres o mujeres de al menos 18 años de edad. b.Pacientes que hayan sufrido un sindrome coronario agudo (incluyendo STEMI o NSTEMI) al menos 30 días antes, c.Tratamiento en curso durante al menos 0 días con terapia dual antiplaquetaria, consistente en aspirina a dosis de 75-160 mg diarios y un inhibidor oral de P2Y12 del mercado: ticagrelor, clopidogrel o prasugrel, en régimen de mantenimiento según FT. d.Libre de episodios hemorrágicos (según definición BARC tipo 2 o mayor), o recurrencias isquémicas. e.Pacientes que hayan firmado el consentimiento informado para participar en el estudio. |
|
E.4 | Principal exclusion criteria |
a.Administration of fibrinolytics or glycoprotein IIb/IIIa inhibitors in the previous 30 days b.major surgery within 30 days or any planned surgical intervention c.active bleeding or previous clinical relevant bleeding or stroke in the last 6 months d.previous intracranial bleeding e.thrombocytopenia <100,000 platelets/ML f.oral anticoagulant therapy g.vasculitis h.any know immunological disorder i.severe hepatic failure j.uncontrolled hypertension (systolic or diastolic arterial pressure >180 mmHg or 120, respectively, despite medical therapy) k.known intolerance to aspirin or to clopidogrel or prasugrel or ticagrelor l.limited life expectancy (e.g. neoplasms others) m.inability to obtain informed consent n.Pregnancy, lactation, or planned pregnancy during the study period. |
a.Administración de fibrinolíticos o de inhibidores de la glicoproteína IIb/IIIa en los 30 días previos b.cirugía mayor en los 30 días previos o intervención quirúrgica planificada c.sangrado activo o sangrado previo o ictus clínicamente relevantes en los últimos 6 meses e.trombocitopenia <100,000 plaquetas /ml f.terapia anticoagulante oral therapy g.vasculitis h.cualquier enfermedad inmunólógica que conocida i.fallo hepático agudo j.hipertensión no controlada (presión arterial sistólica o diastólica >180 mmHg o 120, respectivamente, a pesar de la medicación) k.intolerancia conocida a aspirina o a clopidogrel o prasugrel o ticagrelor l.expectativa de vida limitada (ej. neoplasias, otros) m.incapacidad para obtener el consentimiento informado n.Embarazo, lactancia, o previsión de embarazo durante el período del estudio |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Changes in Reactive hyperemia Index (RHI) at treatment steady state, assessed with Endopath system (Endopath; Itamar Medical Ltd., Cesarea, Israel) as compared to 1-2 hour(s) after loading dose. |
Cambios en el índice de hiperemia reactiva (RHI: Endopath system) en estado estacionario de tratamiento, comparado con 1-2 horas después de la ingesta de la dosis de carga de medicamento. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 months (90 days) |
3 meses (90 días) |
|
E.5.2 | Secondary end point(s) |
? Changes in reactive hyperemia index (RHI) 1-2 hour(s) after the oral P2Y12 inhibitor loading, ? Changes in asymmetrical dimethylarginine (ADMA), ? Changes in micro-albuminuria, ? Changes in von willebrand factor antigen, ? Changes in C-reactive protein, ? Changes in soluble fms-like tyrosine kinase-1 (sFLT-1), ? Changes in intercellular cell adhesion molecule-1 (ICAM-1), ? Changes in vascular cell adhesion molecule-1 (VCAM-1)], ? Changes in residual platelet reactivity assessed in terms of PRU and ARU, ? changes in endothelial function, ? changes in prothrombin fragment 1+2, ? changes in A fibrinopeptide ? changes thrombin?antithrombin complex (TAT) ? changes adenosine plasma concentration (APC), ? changes Ticagrelor and AR-C124910XX levels . |
? Cambios en el índice de hiperemia reactiva (RHI) 1-2 horas después de la ingesta del inhibidor de P2Y12, ? Cambios en dimetilarginina asimétrica (ADMA), ? Cambios en la micro-albuminuria, ? Cambios en el antígeno del factor von Willebrand, ? Cambios en la proteína C-reactiva, ? Cambios en tirosina cinasa 1 símil-fms soluble (sFlt-1), ? Cambios en la molécula de adhesión intercelular-1 (ICAM-1), ? Cambios en la adhesión celular vascular molécula-1 (VCAM-1)] ? Cambios en la reactividad plaquetaria residual evaluada en términos de PRU y ARU, ? cambios en función endotelial, ? cambios en niveles de fragmentos de protrombina 1 + 2, ? cambios en niveles fibrinopéptido A ? cambios en niveles del complejo trombina-antitrombina (TAT) ? cambios en niveles de la concentración plasmática de adenosina (APC), ? cambios en niveles de ticagrelor y AR-C124910XX. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 months (90 days) |
3 meses (90 días) |
|
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 | No |
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 | Yes |
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 | 3 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |