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Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction (IMPRESSION)

12 de agosto de 2017 actualizado por: Jacek Kubica, Collegium Medicum w Bydgoszczy

A Randomized, Double-blind Study Evaluating the Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor and Its Active Metabolite (AR-C124910XX) in Patients With ST-segment Elevation Myocardial Infarction and Non-ST-segment Elevation Myocardial Infarction.

The purpose of the IMPRESSION study is to determine whether intravenous administration of morphine prior to ticagrelor administration in ST-segment elevation myocardial infarction (STEMI) patients and in non-ST-segment elevation myocardial infarction (NSTEMI) patients alters the plasma concentrations of ticagrelor and its active metabolite and whether it is associated with any negative impact on the antiplatelet effect of ticagrelor.

Descripción general del estudio

Descripción detallada

The European Society of Cardiology and American Heart Association guidelines recommend use of morphine as a treatment of choice for pain relief in STEMI patients. However, this recommendation, although strong, is only based on expert consensus (class of recommendation I, level of evidence C). Morphine, apart from its analgesic effects, also alleviates the work of breathing and reduces anxiety. On the other hand, despite its favorable analgesic and sedative actions, morphine also exerts adverse effects, which include hypotension, bradycardia, respiratory depression, vomiting and reduction of gastrointestinal motility. Some of the previously listed morphine's side effects could affect the intestinal absorption and thus pharmacokinetics and pharmacodynamics of orally administered drugs which are concomitantly used with morphine. At present, no pharmacokinetic and pharmacodynamic data regarding the concurrent use of morphine and P2Y12 blockers in the STEMI or NSTEMI setting are available. Therefore, evidence-based verification of morphine's influence on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) could provide a valuable insight in the knowledge regarding modern acute myocardial infarction management.

Predefined subanalysis: aimed to investigate which one of platelet reactivity assessment methods utilized in the study (VASP assay, MEA, LTA, VerifyNow) best reflects concentration of ticagrelor and its active metabolite (AR-C124910XX).

Since there is no reference study examining pharmacokinetics of ticagrelor in STEMI or NSTEMI patients, we decided to perform an internal pilot study of approximately 30 patients (15 patients for each arm) for estimating the final sample size.

Tipo de estudio

Intervencionista

Inscripción (Actual)

74

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

    • Kujawsko-pomorskie
      • Bydgoszcz, Kujawsko-pomorskie, Polonia, 85-094
        • Cardiology Department, Dr. A. Jurasz University Hospital

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 80 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • provision of informed consent prior to any study specific procedures
  • diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction
  • male or non-pregnant female, aged 18-80 years old
  • provision of informed consent for angiography and PCI

Exclusion Criteria:

  • chest pain described by the patient as unbearable or patient's request for analgesics
  • prior morphine administration during the current STEMI or NSTEMI
  • treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment
  • hypersensitivity to ticagrelor
  • current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin
  • active bleeding
  • history of intracranial hemorrhage
  • recent gastrointestinal bleeding (within 30 days)
  • history of coagulation disorders
  • platelet count less than <100 x10^3/mcl
  • hemoglobin concentration less than 10.0 g/dl
  • history of moderate or severe hepatic impairment
  • history of major surgery or severe trauma (within 3 months)
  • patients considered by the investigator to be at risk of bradycardic events
  • second or third degree atrioventricular block during screening for eligibility
  • history of asthma or severe chronic obstructive pulmonary disease
  • patient required dialysis
  • manifest infection or inflammatory state
  • Killip class III or IV during screening for eligibility
  • respiratory failure
  • history of severe chronic heart failure (NYHA class III or IV)
  • concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
  • body weight below 50 kg

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: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
Dosis de carga de 180 mg
Otros nombres:
  • Brilique
IV bolus injection
Otros nombres:
  • Sulfato de morfina
Comparador de placebos: Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
Dosis de carga de 180 mg
Otros nombres:
  • Brilique
IV bolus injection
Otros nombres:
  • Cloruro de sodio 0,9%

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
Periodo de tiempo: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose
prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
Periodo de tiempo: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose
prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Maximum Concentration of Ticagrelor
Periodo de tiempo: 12 hours
Maximum concentration (Cmax) of ticagrelor
12 hours
Maximum Concentration of AR-C124910XX
Periodo de tiempo: 12 hours
Maximum concentration (Cmax) of AR-C124910XX
12 hours
Time to Maximum Concentration for Ticagrelor
Periodo de tiempo: 12 hours
Time to maximum concentration (Tmax) for ticagrelor
12 hours
Time to Maximum Concentration for AR-C124910XX
Periodo de tiempo: 12 hours
Time to maximum concentration (Tmax) for AR-C124910XX
12 hours
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
Periodo de tiempo: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose
prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)
Periodo de tiempo: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose
prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
Platelet Reactivity Index Assessed by VASP Assay
Periodo de tiempo: prior to the initial ticagrelor dose
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
prior to the initial ticagrelor dose
Platelet Reactivity Index Assessed by VASP Assay
Periodo de tiempo: 30 minutes post ticagrelor dose
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
30 minutes post ticagrelor dose
Platelet Reactivity Index Assessed by VASP Assay
Periodo de tiempo: 1 hour post ticagrelor dose
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
1 hour post ticagrelor dose
Platelet Reactivity Index Assessed by VASP Assay
Periodo de tiempo: 2 hours post ticagrelor dose
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
2 hours post ticagrelor dose
Platelet Reactivity Index Assessed by VASP Assay
Periodo de tiempo: 3 hours post ticagrelor dose
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
3 hours post ticagrelor dose
Platelet Reactivity Index Assessed by VASP Assay
Periodo de tiempo: 4 hours post ticagrelor dose
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
4 hours post ticagrelor dose
Platelet Reactivity Index Assessed by VASP Assay
Periodo de tiempo: 6 hours post ticagrelor dose
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
6 hours post ticagrelor dose
Platelet Reactivity Index Assessed by VASP Assay
Periodo de tiempo: 12 hours post ticagrelor dose
Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
12 hours post ticagrelor dose
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Periodo de tiempo: prior to the initial ticagrelor dose
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
prior to the initial ticagrelor dose
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Periodo de tiempo: 30 minutes post ticagrelor dose
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
30 minutes post ticagrelor dose
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Periodo de tiempo: 1 hour post ticagrelor dose
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
1 hour post ticagrelor dose
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Periodo de tiempo: 2 hours post ticagrelor dose
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
2 hours post ticagrelor dose
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Periodo de tiempo: 3 hours post ticagrelor dose
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
3 hours post ticagrelor dose
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Periodo de tiempo: 4 hours post ticagrelor dose
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
4 hours post ticagrelor dose
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Periodo de tiempo: 6 hours post ticagrelor dose
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
6 hours post ticagrelor dose
Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Periodo de tiempo: 12 hours post ticagrelor dose
Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
12 hours post ticagrelor dose
P2Y12 Reaction Units Assessed by VerifyNow
Periodo de tiempo: prior to the initial ticagrelor dose
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
prior to the initial ticagrelor dose
P2Y12 Reaction Units Assessed by VerifyNow
Periodo de tiempo: 30 minutes post ticagrelor dose
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
30 minutes post ticagrelor dose
P2Y12 Reaction Units Assessed by VerifyNow
Periodo de tiempo: 1 hour post ticagrelor dose
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
1 hour post ticagrelor dose
P2Y12 Reaction Units Assessed by VerifyNow
Periodo de tiempo: 2 hours post ticagrelor dose
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
2 hours post ticagrelor dose
P2Y12 Reaction Units Assessed by VerifyNow
Periodo de tiempo: 3 hours post ticagrelor dose
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
3 hours post ticagrelor dose
P2Y12 Reaction Units Assessed by VerifyNow
Periodo de tiempo: 4 hours post ticagrelor dose
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
4 hours post ticagrelor dose
P2Y12 Reaction Units Assessed by VerifyNow
Periodo de tiempo: 6 hours post ticagrelor dose
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
6 hours post ticagrelor dose
P2Y12 Reaction Units Assessed by VerifyNow
Periodo de tiempo: 12 hours post ticagrelor dose
P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
12 hours post ticagrelor dose
Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP
Periodo de tiempo: 2 hours
Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP
2 hours
Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA
Periodo de tiempo: 2 hours
Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA
2 hours
Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow
Periodo de tiempo: 2 hours
Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow
2 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP
Periodo de tiempo: 12 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP
12 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA
Periodo de tiempo: 12 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA
12 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow
Periodo de tiempo: 12 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
12 hours

Colaboradores e Investigadores

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

Investigadores

  • Investigador principal: Prof. Jacek Kubica, MD, PhD, Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu

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 2014

Finalización primaria (Actual)

1 de junio de 2015

Finalización del estudio (Actual)

1 de junio de 2015

Fechas de registro del estudio

Enviado por primera vez

14 de agosto de 2014

Primero enviado que cumplió con los criterios de control de calidad

14 de agosto de 2014

Publicado por primera vez (Estimar)

15 de agosto de 2014

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

12 de septiembre de 2017

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

12 de agosto de 2017

Última verificación

1 de agosto de 2017

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 Ticagrelor

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