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

Vaud University Hospital Center

Status: Completed

Conditions: Acute Myocardial Infarction

Treatments: Drug: Ticagrelor; Drug: Fentanyl; Drug: Morphine; Drug: Unfractioned Heparin; Drug: Aspirin; Procedure: Primary PCI

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02531165

ESR14-10591

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 38 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

38 participants in 2 patient groups

Morphine

Experimental group

Description:

* Pre-hospital Ticagrelor 180 mg loading dose orally. * Morphine, initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required. * Aspirin 500 mg loading dose orally (or intravenously). * Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT \>250 sec during PCI are allowed. * Primary PCI.

Treatment:

Drug: Aspirin

Drug: Morphine

Drug: Unfractioned Heparin

Procedure: Primary PCI

Drug: Ticagrelor

Fentanyl

Experimental group

Description:

* Pre-hospital Ticagrelor 180 mg loading dose orally. * Fentanyl, initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required. * Aspirin 500 mg loading dose orally (or intravenously). * Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT \>250 sec during PCI are allowed. * Primary PCI.

Treatment:

Drug: Fentanyl

Drug: Aspirin

Drug: Unfractioned Heparin

Procedure: Primary PCI

Drug: Ticagrelor