Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

Endothelium, Stenting, and Antiplatelet Therapy (EST) - Clopidogrel, Prasugrel, Ticagrelor Study (EST)

4 de septiembre de 2016 actualizado por: Tommaso Gori, Johannes Gutenberg University Mainz

Effects of Clopidogrel vs Prasugel vs Ticagrelor on Endothelial Function, Inflammatory and Oxidative Stress Parameters and Platelet Function in Patients Undergoing Coronary Artery Stenting. A Randomised, Prospective Study.

Endothelial dysfunction is an important predictor - and a determinant - of adverse clinical outcome. Endothelial function is impaired by coronary artery stenting, a stud from our group has shown that it can be improved by platelet inhibition using clopidogrel. However, clopidogrel unresponsiveness is a known problem, and it has been show that the endothelial effects of clopidogrel tend to wane upon prolonged treatment. Whether a more effective anti-platelet therapy is able to prevent/improve not only thrombotic events but also endothelial dysfunction, with potential positive impact on clinical outcome in patients undergoing coronary artery stenting, is an important hypothesis that needs to be further investigated. To date, evidence regarding "ancillary" (non-platelet-dependent) effects of antiaggregant drugs is very limited. For instance, while their antiplatelet effects, and their beneficial effects in patients with acute coronary syndromes, have been clearly demonstrated in multicentric trials, it remains to be shown whether these drugs also protect endothelial function. Interestingly, some authors suggest that the mortality benefit observed in the PLATO study is at least in part independent of direct antiplatelet effects. No study, to date, has tested the effects of prasugrel and/or ticagrelor on endothelial function. With the present trial, the investigators plan to test the effect of clopidogrel, prasugrel and ticagrelor on endothelial function before and up to 4 weeks after coronary artery stenting. This study will provide important pathophysiologic insight on the relationship between platelet aggregation and endothelial function, two parameters that have been shown to influence patients' prognosis.

Descripción general del estudio

Tipo de estudio

Intervencionista

Inscripción (Actual)

126

Fase

  • Fase 4

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

      • Mainz, Alemania, 55131
        • 2 Medical Clinic

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 75 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • - 18-75 years old consecutive patients undergoing coronary angiography and stenting at the University Medical Centre Mainz
  • A coronary lesion (and patient) amenable to treatment with drug eluting stent
  • Ability of subject to understand character and individual consequences of clinical trial
  • Signed and dated informed consent of the subject must be available before start of any specific trial procedures.
  • Negative pregnancy test of women with childbearing potential

Exclusion Criteria:

  • Subjects presenting 1 or more of the following criteria will not be enrolled in the trial:
  • Patients with elevated (> 5 times upper normal limit) C-reactive protein level prior to stenting
  • Patients in whom therapy with long-acting nitrates cannot be suspended prior to endothelial function measurements
  • An acute coronary syndrome treated with coronary stenting within the last 4 weeks
  • Patients with known inflammatory/infective diseases
  • Patients with severe extracardiac diseases limiting life expectancy
  • Known heart failure (LV-EF ≤ 40% AND NYHA III-IV)
  • PCI or coronary By-Pass surgery within the last 4 weeks, pre-existing ongoing treatment with any of the study treatments.
  • History of cerebrovascular events (stroke)
  • Known renal dysfunction (serum creatinine ≥ 1.8mg/dl in women, ≥ 2.0mg/dl in men)
  • Serum potassium > 5.5mmol/l
  • Known hepatic impairment (AST, ALT > 3 times upper limit of normal)
  • Changes in the ß-blocker, statin or ACE or angiotensin-receptor blocker inhibitor treatment within the past 2 weeks
  • Pregnancy and lactation, inadequate contraception
  • Body weight < 60kg
  • Active bleeding
  • Therapy with CYP3A4 inhibitors (ketoconazole, protease inhibitors, macrolide antibiotics)
  • Therapy with anticoagulants: phenprocoumone, warfarin, dabigatran, rivaroxaban
  • History of hypersensitivity to any of the investigational medicinal products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
  • Ongoing participation in other clinical trials or within the last 3 months, or ongoing therapy with one of the study medications.
  • Medical or psychological condition that would not permit completion of the trial or signing of informed consent.
  • Patients with acute ST-elevation myocardial infarction

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Ciencia básica
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Único

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Ticagrelor
Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting
All patients will receive a drug eluting stent as clinically indicated.
Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting
Comparador activo: Clopidogrel
Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting.
All patients will receive a drug eluting stent as clinically indicated.
Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting.
Comparador activo: Prasugrel
Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting
All patients will receive a drug eluting stent as clinically indicated.
Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change in FMD
Periodo de tiempo: baseline and 1 month
The primary endpoint is the change in flow-mediated dilation (FMD) (comparison before treatment versus after treatment and stenting) in the three study groups. The mean FMD across the three measurements (1 day, 1 week, 1 month) performed after coronary artery stenting will be compared to the FMD value before drug administration and stenting.
baseline and 1 month

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
FMD 2 hours after loading dose
Periodo de tiempo: baseline and 2 hours after loading dose
Change in FMD 2 hours after the administration of the study drug
baseline and 2 hours after loading dose
L-FMC at 2 hours after the loading dose
Periodo de tiempo: baseline and 2 hours
change in L-FMC at two hours after the loading dose
baseline and 2 hours
L-FMC 1 month after loading dose
Periodo de tiempo: baseline and 1 day after stenting
change in flow-mediated constriction (L-FMC) (comparison before treatment versus after treatment and stenting) in the three study groups. The mean L-FMC across the three measurements (1 day, 1 week, 1 month) performed after coronary artery stenting will be compared to the value before drug administration and stenting
baseline and 1 day after stenting
Safety and tolerability
Periodo de tiempo: from baseline to 1 month after enrollment
Number of patients with adverse events.
from baseline to 1 month after enrollment

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Investigadores

  • Silla de estudio: Thomas Munzel, MD Prof., University Medical Center Mainz

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de agosto de 2012

Finalización primaria (Actual)

1 de julio de 2016

Finalización del estudio (Actual)

1 de septiembre de 2016

Fechas de registro del estudio

Enviado por primera vez

4 de septiembre de 2012

Primero enviado que cumplió con los criterios de control de calidad

3 de octubre de 2012

Publicado por primera vez (Estimar)

4 de octubre de 2012

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

7 de septiembre de 2016

Última actualización enviada que cumplió con los criterios de control de calidad

4 de septiembre de 2016

Última verificación

1 de septiembre de 2016

Más información

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Ensayos clínicos sobre Coronary stenting

Suscribir