Acute Myocardial Infarction
Conditions
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.
Interventions
DRUGFentanyl
Analgesia protocol using Fentanyl (initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required).
DRUGMorphine
Analgesia protocol using Morphine (initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required).
DRUGTicagrelor
Pre-hospital Ticagrelor loading dose of 180 mg administered orally, followed by 90 mg bid
DRUGAspirin
500 mg loading dose orally (or intravenously), followed by 100 mg od
5'000 IU loading dose intravenously, additional doses to achieve an ACT \>250 sec during PCI are allowed.
PROCEDUREPrimary PCI
Primary PCI with stent implantation according to the guidelines of the European Society of Cardiology.
Sponsors
AstraZeneca
Centre Hospitalier Universitaire Vaudois
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU) | 2 hours after loading dose of Ticagrelor |
Secondary
| Measure | Time frame |
|---|---|
| High on Treatment Platelet Reactivity (HTPR) rates | 0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor |
| 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 |
| Residual PR by PRU | 0, 1, 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 |
| Proportion of patients without Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography | at 2 hours |
| Area under the plasma concentration-time curve of Ticagrelor | at 1, 2, 4, 6 and 12 hours |
Countries
Switzerland
Outcome results
None listed