E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute myocardial infarction |
infarto agudo de miocardio |
|
E.1.1.1 | Medical condition in easily understood language |
acute myocardial infarction |
infarto agudo de miocardio |
|
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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac 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 determine the effectiveness of combination therapy with RIC and exenatide to limit MI size in patients with STEMI receiving pPCI. |
? Determinar la efectividad de la terapia combinada con RIC y exenatida para limitar el tamaño del infarto en pacientes con STEMI que reciben pPCI. |
|
E.2.2 | Secondary objectives of the trial |
? To evaluate the safety of combination therapy with RIC and exenatide in patients with STEMI. ? To determine the effects of the study treatments on the rate of effective myocardial reperfusion, left ventricular end-diastolic volume and ejection fraction, and microvascular obstruction (MVO). ? To evaluate the effect of the study treatments on the frequency of MACE. ? To assess the impact of RIC and exenatide, alone and in combination, through a phase III randomised controlled clinical trial on MI size in patients with STEMI |
? Evaluar la seguridad de la terapia combinada con RIC y exenatida en pacientes con STEMI. ? Determinar los efectos del tratamiento de estudio sobre la tasa de efectividad de la reperfusión miocárdica, el volumen telediastólico, y la fracción de eyección el ventrículo izquierdo y el grado de obstrucción microvascular. ? Evaluar el efecto del tratamiento de estudio en la frecuencia de aparición de MACE. ? Evaluar el impacto de RIC y exenatida, sola y en combinación a través de un ensayo clínico randomizado, controlado en el tamaño del infarto en pacientes con STEMI. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Men or women > =18 years of age ? STEMI characterized by 2 mm ST elevation in 2 or more V1 through V4 leads or presumed new left bundle branch block with minimum of 1 mm concordant ST elevation or 1 mV ST-segment elevation in the limb lead (II, III and aVF, I, aVL) and V4?V6. ? Patients presenting within 6 hours of chest pain. |
? Mujeres y Hombres > =18 años ? STEMI caracterizado por 2 mm de elevación del segment ST en 2 o más derivaciones entre V1 y V4 o sospecha de Nuevo bloqueo de rama izquierda con un mínimo de 1 mm de elevación del segmento ST concordante o 1 mV de elevación del segmento ST en las derivaciones de las extremidades (II, III y aVF, I, aVL) y V4?V6. ? Pacientes que llegan al hospital dentro de las primeras 6 horas del inicio del dolor torácico. |
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E.4 | Principal exclusion criteria |
? Known hypersensitivity to exenatide or any of the excipients ? Known contraindication to CMR imaging such as significant claustrophobia, severe allergy to gadolinium chelate contrast, severe renal insufficiency (defined as estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2), presence of CMR contraindicated implanted devices (e.g., pacemaker, implanted cardiac defibrillator, cardiac resynchronization therapy device, cochlear implant), embedded metal objects (e.g., shrapnel), or any other contraindication for CMR. ? Assumed life expectancy < 1 year e.g. due to non-cardiac disease. ? TIMI flow grade > 1 at the time of diagnostic coronary angiography. These patients will be excluded from the analysis of infarct size but will be included in the safety analysis. ? Pregnant women ? Patients with loss of consciousness or confused, not able to read the information and to sign the writing consent ? Patients with oro-tracheal intubation ? Patients with cardiogenic shock persisting 48 hours after reperfusion |
? Hipersensibilidad conocida a la exenatida o a alguno de los excipientes ? Contraindicación conocida a la Cardioresonancia magnética, como claustrofobia significativa, alergia severa al contraste de gadolinio, insuficiencia renal severa ( definida como una tasa de filtración glomerular estimada [eGFR] <30 mL/min/1.73 m2), presencia de dispositivos implantables contraindicados para la cardioresonancia como resincronizadores, implantes cocleares, objetos metálicos en el cuerpo como metralla u otra s contraindicaciones. ? Esperanza de vida < 1 año debida, por ejemplo, a enfermedad maligna. ? Grado TIMI flow > 1 en el momento de la angiografía coronaria diagnóstica. Estos pacientes serán excluídos del análisis del tamaño del infarto pero serán incluídos en el análisis de seguridad. ? Mujeres embarazadas. ? Pacientes confusos o con pérdida de consciencia que no puedan entender la información y firmar el consentimiento ? Pacientes con intubación orotraqueal ? Shock cardiogénico persistente 48 horas después de la reperfusión |
|
E.5 End points |
E.5.1 | Primary end point(s) |
MI, measured by late gadolinium enhancement in CMRI 2-7 days after pPCI, and expressed as percent of left ventricular mass. |
Tamaño del infarto de miocardio medido por realce tardío de gadolinio en la cardioresonancia magnética entre 2-7 días después del intervencionismo cardíaco percutáneo expresado como porcentaje de la masa ventricular izquierda. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2-7 days after pPCI |
2-7 dia después intervencionismo primario percutáneo |
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E.5.2 | Secondary end point(s) |
a) Myocardial salvage index defined as the difference between infarct size and area at risk, defined by the T2 CMRI and expressed as a percent of total LV mass, divided by the area at risk. b) Transmurality index, defined as the ratio of the mass of myocardium showing late gadolinium enhancement to the mass of the myocardial segment containing it. c) Markers of successful myocardial reperfusion: ST-segment resolution 90 minutes post-pPCI , TIMI flow and frame-count post-pPCI , and TIMI blush grade . d) LV end-diastolic volume and LVEF, as determined by CMRI. e) Volume of myocardium with MVO determined by late gadolinium enhancement expressed as percent of infarct size. f) MACE rate during hospitalization, defined as death, non-fatal myocardial rupture, or appearance or worsening of heart failure during the hospitalization period. |
a) índice de recuperación miocárdica definido como la diferencia entre el tamaño del infarto y el área en riesgo, definido por la señal hiperintensa en la imagen pesada en T2 de la cardioresonancia magética y expresado como un porcentaje de la masa total del ventrículo izquierdo, dividida por el área en riesgo. b) Índice de transmuralidad, definida como la relación de la masa de miocardio que muestra realce tardío de gadolinio respecto a la masa del segmento de miocardio que lo contiene. c) Los marcadores de éxito de reperfusión miocárdica: resolución del segmento ST a los 90 minutos post-Intervencionismo Cardíaco percutáneo, flujo TIMI y frame-count Intervencionismo Cardíaco Percútaneo y grado TIMI blush. d) el volumen telediastólico final del VI y la FEVI, según lo determinado por la CRM. e) Volumen de miocardio con obstrucción microvascular eterminado por realce tardío de gadolinio expresado como porcentaje del tamaño del infarto. f) la tasa MACE durante la hospitalización, que se define como la muerte, la rotura de miocardio no fatal, apariencia o el empeoramiento de la insuficiencia cardíaca durante el período de hospitalización. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2-7 days after pPCI |
2-7 dia después intervencionismo primario percutáneo |
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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 | 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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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
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Last patient`s last visit |
Ultima visita del último paciente |
|
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 | 36 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |