Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction
Condition: ST-segment Elevation Myocardial Infarction; Non-ST-segment Elevation Myocardial Infarction; VA Drug Interactions
MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction
Intervention: Morphine; Placebo; Ticagrelor
Intervention description: IV bolus injection; IV bolus injection; 180 mg loading dose
Intervention MeSH terms: Morphine; Ticagrelor
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: ST-segment elevation myocardial infarction; non-ST-segment elevation myocardial infarction; ticagrelor; morphine; pharmacokinetics; pharmacodynamics; drug interactions; VASP assay; Multiple Electrode Aggregometry; VerifyNow

Summary:

      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.
    

Eligibility criteria:

        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