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

12. srpna 2017 aktualizováno: 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.

Přehled studie

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

Intervenční

Zápis (Aktuální)

74

Fáze

  • Fáze 4

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let až 80 let (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

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

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

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
180 mg nasycovací dávka
Ostatní jména:
  • Brilique
IV bolus injection
Ostatní jména:
  • Morfin sulfát
Komparátor placeba: Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
180 mg nasycovací dávka
Ostatní jména:
  • Brilique
IV bolus injection
Ostatní jména:
  • Chlorid sodný 0,9%

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
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

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
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
Časové okno: 12 hours
Maximum concentration (Cmax) of ticagrelor
12 hours
Maximum Concentration of AR-C124910XX
Časové okno: 12 hours
Maximum concentration (Cmax) of AR-C124910XX
12 hours
Time to Maximum Concentration for Ticagrelor
Časové okno: 12 hours
Time to maximum concentration (Tmax) for ticagrelor
12 hours
Time to Maximum Concentration for AR-C124910XX
Časové okno: 12 hours
Time to maximum concentration (Tmax) for AR-C124910XX
12 hours
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
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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 12 hours
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
12 hours

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Vyšetřovatelé

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

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. srpna 2014

Primární dokončení (Aktuální)

1. června 2015

Dokončení studie (Aktuální)

1. června 2015

Termíny zápisu do studia

První předloženo

14. srpna 2014

První předloženo, které splnilo kritéria kontroly kvality

14. srpna 2014

První zveřejněno (Odhad)

15. srpna 2014

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

12. září 2017

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

12. srpna 2017

Naposledy ověřeno

1. srpna 2017

Více informací

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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