Platelet Inhibition After Pre-hospital Ticagrelor Using Fentanyl Compared to Morphine in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Not Applicable
Completed
- Conditions
- Acute Myocardial Infarction
- Interventions
- Procedure: Primary PCI
- Registration Number
- NCT02531165
- Lead Sponsor
- Centre Hospitalier Universitaire Vaudois
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fentanyl Unfractioned Heparin * 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. Fentanyl Primary PCI * 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. Morphine Primary PCI * 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. Morphine Unfractioned Heparin * 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. Morphine Morphine * 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. Morphine Ticagrelor * 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. Morphine Aspirin * 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. Fentanyl Ticagrelor * 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. Fentanyl Fentanyl * 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. Fentanyl Aspirin * 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.
- Primary Outcome Measures
Name Time Method Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU) 2 hours after loading dose of Ticagrelor
- Secondary Outcome Measures
Name Time Method Area under the plasma concentration-time curve of Ticagrelor at 1, 2, 4, 6 and 12 hours Peak plasma concentration (Cmax) of Ticagrelor and AR-C124910XX at 1, 2, 4, 6 and 12 hours Time to peak plasma concentration (tmax) of Ticagrelor and AR-C124910XX at 1, 2, 4, 6 and 12 hours Proportion of patients without Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography at 2 hours Residual PR by PRU 0, 1, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor High on Treatment Platelet Reactivity (HTPR) rates 0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor Proportion of patients with 70% or greater resolution of the ST-segment elevation before PCI at 2 hours
Trial Locations
- Locations (1)
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Vaud, Switzerland