Platelet Inhibition After Pre-hospital Ticagrelor Using Fentanyl Compared to Morphine in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Comparison of Analgesia With Fentanyl and Morphine on Platelet Inhibition After Pre-hospital Ticagrelor Administration in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Prospective, randomized, open-label, single-center, investigator-initiated trial, including patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) within 12 hours of the symptom's onset. The study aims to compare platelet inhibition (pharmacodynamics and pharmacokinetics) of pre-hospital Ticagrelor in patients with STEMI according to two different analgesia protocols using Fentanyl or Morphine.

Consecutive patients with acute STEMI within 12 hours of the symptoms' onset and candidates for PPCI will be screened for inclusion in the study. Eligible patients who require analgesia for the relief of acute chest pain, defined as Visual Analogue Scale ≥3, will be randomized in a 1:1 ratio into one of the two treatment arms to receive analgesia with either Morphine or Fentanyl following administration of a pre-hospital loading dose of Ticagrelor. Randomized patients will undergo primary PCI and managed according to the current guidelines of the European Society of Cardiology. Blood samples (10 ml) will be collected at 0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor to assess platelet inhibition using the VerifyNow P2Y12 function and the Vasodilator-Stimulated-phosphoprotein Phosphorylation (VASP) assays, plasma concentration of Ticagrelor and its active metabolite (AR-C124910XX) using a validated liquid chromatography/mass spectrometry detection method and the procoagulant action of platelets.

Inclusion Criteria:

• Age >18-year-old
• STEMI within 12 hours of symptoms' onset eligible for primary PCI with stent implantation.
• Patient able to give written informed consent.

Exclusion Criteria:

• Contraindication, intolerance or hypersensitivity to Ticagrelor, or any excipients
• Contraindication, intolerance or hypersensitivity to Morphine, Fentanyl, or any excipients
• Active bleeding or bleeding diathesis
• History of intracranial haemorrhage
• Chronic oral anticoagulation treatment
• Previous antiplatelet treatment
• Contraindications to antiplatelet therapy
• Severe renal insufficiency (creatinine clearance <30 mL/min)
• Severe hepatic dysfunction
• Severe chronic obstructive pulmonary disease
• Periprocedural glycoprotein IIb/IIIa inhibitors administration
• Relevant haematological disease
• Patient who is currently, plans, or has been enrolled in another clinical study involving use of an investigational drug or device within the prior 30 days.
• If female, patient pregnant or breastfeeding.