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- Ensaio Clínico NCT02217878
Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction (IMPRESSION)
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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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 estudo
Inscrição (Real)
Estágio
- Fase 4
Contactos e Locais
Locais de estudo
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Kujawsko-pomorskie
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Bydgoszcz, Kujawsko-pomorskie, Polônia, 85-094
- Cardiology Department, Dr. A. Jurasz University Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Comparador Ativo: Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
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Dose de ataque de 180 mg
Outros nomes:
IV bolus injection
Outros nomes:
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Comparador de Placebo: Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
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Dose de ataque de 180 mg
Outros nomes:
IV bolus injection
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
Prazo: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
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Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose
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prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
Prazo: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
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Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose
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prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
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Maximum Concentration of Ticagrelor
Prazo: 12 hours
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Maximum concentration (Cmax) of ticagrelor
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12 hours
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Maximum Concentration of AR-C124910XX
Prazo: 12 hours
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Maximum concentration (Cmax) of AR-C124910XX
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12 hours
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Time to Maximum Concentration for Ticagrelor
Prazo: 12 hours
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Time to maximum concentration (Tmax) for ticagrelor
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12 hours
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Time to Maximum Concentration for AR-C124910XX
Prazo: 12 hours
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Time to maximum concentration (Tmax) for AR-C124910XX
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12 hours
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Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
Prazo: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose
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prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)
Prazo: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose
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prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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Platelet Reactivity Index Assessed by VASP Assay
Prazo: prior to the initial ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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prior to the initial ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
Prazo: 30 minutes post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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30 minutes post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
Prazo: 1 hour post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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1 hour post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
Prazo: 2 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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2 hours post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
Prazo: 3 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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3 hours post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
Prazo: 4 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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4 hours post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
Prazo: 6 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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6 hours post ticagrelor dose
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Platelet Reactivity Index Assessed by VASP Assay
Prazo: 12 hours post ticagrelor dose
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Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
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12 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Prazo: prior to the initial ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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prior to the initial ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Prazo: 30 minutes post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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30 minutes post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Prazo: 1 hour post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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1 hour post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Prazo: 2 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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2 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Prazo: 3 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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3 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Prazo: 4 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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4 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Prazo: 6 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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6 hours post ticagrelor dose
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Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Prazo: 12 hours post ticagrelor dose
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Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
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12 hours post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
Prazo: prior to the initial ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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prior to the initial ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
Prazo: 30 minutes post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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30 minutes post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
Prazo: 1 hour post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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1 hour post ticagrelor dose
|
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P2Y12 Reaction Units Assessed by VerifyNow
Prazo: 2 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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2 hours post ticagrelor dose
|
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P2Y12 Reaction Units Assessed by VerifyNow
Prazo: 3 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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3 hours post ticagrelor dose
|
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P2Y12 Reaction Units Assessed by VerifyNow
Prazo: 4 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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4 hours post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
Prazo: 6 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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6 hours post ticagrelor dose
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P2Y12 Reaction Units Assessed by VerifyNow
Prazo: 12 hours post ticagrelor dose
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P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
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12 hours post ticagrelor dose
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Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP
Prazo: 2 hours
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Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP
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2 hours
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Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA
Prazo: 2 hours
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Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA
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2 hours
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Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow
Prazo: 2 hours
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Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow
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2 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP
Prazo: 12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP
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12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA
Prazo: 12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA
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12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow
Prazo: 12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
|
12 hours
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Prof. Jacek Kubica, MD, PhD, Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
Publicações e links úteis
Publicações Gerais
- Kubica J, Adamski P, Ostrowska M, Sikora J, Kubica JM, Sroka WD, Stankowska K, Buszko K, Navarese EP, Jilma B, Siller-Matula JM, Marszall MP, Rosc D, Kozinski M. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016 Jan 14;37(3):245-52. doi: 10.1093/eurheartj/ehv547. Epub 2015 Oct 21.
- Kubica J, Adamski P, Ostrowska M, Kozinski M, Obonska K, Laskowska E, Obonska E, Grzesk G, Winiarski P, Paciorek P. Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients with Acute Myocardial Infarction (IMPRESSION): study protocol for a randomized controlled trial. Trials. 2015 Apr 29;16:198. doi: 10.1186/s13063-015-0724-z.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Isquemia
- Processos Patológicos
- Necrose
- Isquemia do miocárdio
- Doenças cardíacas
- Doenças cardiovasculares
- Doenças Vasculares
- Infarto do miocárdio
- Infarte
- Infarto do Miocárdio com Elevação do ST
- Efeitos Fisiológicos das Drogas
- Agentes Neurotransmissores
- Mecanismos Moleculares de Ação Farmacológica
- Depressores do Sistema Nervoso Central
- Agentes do Sistema Nervoso Periférico
- Analgésicos
- Agentes do Sistema Sensorial
- Inibidores da agregação plaquetária
- Antagonistas Purinérgicos dos Receptores P2Y
- Antagonistas dos Receptores P2 Purinérgicos
- Antagonistas purinérgicos
- Agentes Purinérgicos
- Analgésicos, Opioides
- Narcóticos
- Ticagrelor
- Morfina
Outros números de identificação do estudo
- CMUMK202
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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