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
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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.
    

Intervention name(s): Morphine; Placebo; Ticagrelor
Intervention type(s): Drug; Drug; Drug
Intervention description(s): IV bolus injection; IV bolus injection; 180 mg loading dose
Other intervention name(s): Morphine sulfate; Sodium chloride 0,9%; Brilique
Intervention MeSH terms: Morphine; Ticagrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ST-segment elevation myocardial infarction; non-ST-segment elevation myocardial infarction; ticagrelor; morphine; pharmacokinetics; pharmacodynamics; drug interactions; VASP assay; Multiple Electrode Aggregometry; VerifyNow