- ICH GCP
- Registr klinických studií v USA
- Klinická studie 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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 4
Kontakty a umístění
Studijní místa
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Kujawsko-pomorskie
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Bydgoszcz, Kujawsko-pomorskie, Polsko, 85-094
- Cardiology Department, Dr. A. Jurasz University Hospital
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
---|---|
Aktivní komparátor: Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
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180 mg nasycovací dávka
Ostatní jména:
IV bolus injection
Ostatní jména:
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Komparátor placeba: Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
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180 mg nasycovací dávka
Ostatní jména:
IV bolus injection
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
P2Y12 Reaction Units Assessed by VerifyNow
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 2 hours
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Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA
|
2 hours
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Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow
Časové okno: 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
Časové okno: 12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP
|
12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA
Časové okno: 12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA
|
12 hours
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Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow
Časové okno: 12 hours
|
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
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12 hours
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Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Prof. Jacek Kubica, MD, PhD, Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
Publikace a užitečné odkazy
Obecné publikace
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Ischemie
- Patologické procesy
- Nekróza
- Ischémie myokardu
- Srdeční choroba
- Kardiovaskulární choroby
- Cévní onemocnění
- Infarkt myokardu
- Infarkt
- Infarkt myokardu ST elevace
- Fyziologické účinky léků
- Neurotransmiterové látky
- Molekulární mechanismy farmakologického působení
- Depresiva centrálního nervového systému
- Agenti periferního nervového systému
- Analgetika
- Agenti smyslového systému
- Inhibitory agregace krevních destiček
- Antagonisté purinergního P2Y receptoru
- Antagonisté purinergního P2 receptoru
- Purinergní antagonisté
- Purinergní činidla
- Analgetika, opiáty
- Narkotika
- Ticagrelor
- Morfium
Další identifikační čísla studie
- CMUMK202
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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