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

12 agosto 2017 aggiornato da: 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.

Panoramica dello studio

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

Interventistico

Iscrizione (Effettivo)

74

Fase

  • Fase 4

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

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

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

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:
  • Brilique
IV bolus injection
Altri nomi:
  • Morfina solfato
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:
  • Brilique
IV bolus injection
Altri nomi:
  • Cloruro di sodio 0,9%

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

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Investigatori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 agosto 2014

Completamento primario (Effettivo)

1 giugno 2015

Completamento dello studio (Effettivo)

1 giugno 2015

Date di iscrizione allo studio

Primo inviato

14 agosto 2014

Primo inviato che soddisfa i criteri di controllo qualità

14 agosto 2014

Primo Inserito (Stima)

15 agosto 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

12 settembre 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

12 agosto 2017

Ultimo verificato

1 agosto 2017

Maggiori informazioni

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 .

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