- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica 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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 4
Contatti e Sedi
Luoghi di studio
-
-
Kujawsko-pomorskie
-
Bydgoszcz, Kujawsko-pomorskie, Polonia, 85-094
- Cardiology Department, Dr. A. Jurasz University Hospital
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Comparatore attivo: Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
|
Dose di carico di 180 mg
Altri nomi:
IV bolus injection
Altri nomi:
|
|
Comparatore placebo: Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
|
Dose di carico di 180 mg
Altri nomi:
IV bolus injection
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
Lasso di tempo: 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
Lasso di tempo: 12 hours
|
Maximum concentration (Cmax) of ticagrelor
|
12 hours
|
|
Maximum Concentration of AR-C124910XX
Lasso di tempo: 12 hours
|
Maximum concentration (Cmax) of AR-C124910XX
|
12 hours
|
|
Time to Maximum Concentration for Ticagrelor
Lasso di tempo: 12 hours
|
Time to maximum concentration (Tmax) for ticagrelor
|
12 hours
|
|
Time to Maximum Concentration for AR-C124910XX
Lasso di tempo: 12 hours
|
Time to maximum concentration (Tmax) for AR-C124910XX
|
12 hours
|
|
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 12 hours
|
Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
|
12 hours
|
Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Prof. Jacek Kubica, MD, PhD, Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
Pubblicazioni e link utili
Pubblicazioni generali
- 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.
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Ischemia
- Processi patologici
- Necrosi
- Ischemia miocardica
- Malattie cardiache
- Malattia cardiovascolare
- Malattie vascolari
- Infarto miocardico
- Infarto
- Infarto del miocardio con sopraslivellamento del tratto ST
- Effetti fisiologici delle droghe
- Agenti neurotrasmettitori
- Meccanismi molecolari dell'azione farmacologica
- Depressori del sistema nervoso centrale
- Agenti del sistema nervoso periferico
- Analgesici
- Agenti del sistema sensoriale
- Inibitori dell'aggregazione piastrinica
- Antagonisti del recettore purinergico P2Y
- Antagonisti del recettore purinergico P2
- Antagonisti purinergici
- Agenti purinergici
- Analgesici, oppioidi
- Narcotici
- Ticagrelor
- Morfina
Altri numeri di identificazione dello studio
- CMUMK202
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Ticagrelor
-
University of FloridaCompletato
-
Federico II UniversityAdvicePharma GroupCompletatoInfarto miocardico | Disfunsione dell'arteria coronaria | Sindrome coronarica acuta | STEMI | NSTEMIItalia
-
Collegium Medicum w BydgoszczyCompletato
-
AstraZenecaParexelCompletato
-
Centro Hospitalario La ConcepcionReclutamento
-
Montreal Heart InstituteReclutamentoInfarto miocardico | NSTEMI - MI con elevazione del segmento non ST | STEMI (elevazione ST MI)Canada
-
University of FloridaAstraZenecaCompletatoDisfunsione dell'arteria coronariaStati Uniti
-
AstraZenecaCompletatoInfarto miocardico | Ictus | Aterotrombosi | Morte cardiovascolareSvezia, Stati Uniti, Australia, Brasile, Bulgaria, Repubblica Ceca, Francia, Italia, Corea, Repubblica di, Perù, Polonia, Federazione Russa, Sud Africa, Spagna, Tacchino, Regno Unito, Germania, Filippine, Cina, Ungheria, R... e altro ancora
-
Azienda Ospedaliero Universitaria di SassariAstraZenecaCompletatoInfarto del miocardio con sopraslivellamento del tratto ST | NSTEMI - MI con elevazione del segmento non STItalia
-
Sheba Medical CenterCompletatoInfarto del miocardio con sopraslivellamento del tratto ST | Sindromi coronariche acuteIsraele