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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Morphine | Experimental |
|
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| Fentanyl | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fentanyl | Drug | Analgesia protocol using Fentanyl (initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU) | 2 hours after loading dose of Ticagrelor |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Juan F. Iglesias, MD | Centre Hospitalier Universitaire Vaudois | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire Vaudois | Lausanne | Canton of Vaud | 1011 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33347326 | Derived | Iglesias JF, Valgimigli M, Carbone F, Lauriers N, Giorgio Masci P, Degrauwe S. Effects of Fentanyl Versus Morphine on Ticagrelor-Induced Platelet Inhibition in Patients With ST-Segment Elevation Myocardial Infarction: The PERSEUS Randomized Trial. Circulation. 2020 Dec 22;142(25):2479-2481. doi: 10.1161/CIRCULATIONAHA.120.049287. Epub 2020 Dec 21. No abstract available. | |
| 30101278 |
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| Morphine | Drug | Analgesia protocol using Morphine (initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required). |
|
| Ticagrelor | Drug | Pre-hospital Ticagrelor loading dose of 180 mg administered orally, followed by 90 mg bid |
|
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| Aspirin | Drug | 500 mg loading dose orally (or intravenously), followed by 100 mg od |
|
| Unfractioned Heparin | Drug | 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed. |
|
| Primary PCI | Procedure | Primary PCI with stent implantation according to the guidelines of the European Society of Cardiology. |
|
| 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 |
| Area under the plasma concentration-time curve of Ticagrelor | at 1, 2, 4, 6 and 12 hours |
| 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 |
| Derived |
| Degrauwe S, Roffi M, Lauriers N, Muller O, Masci PG, Valgimigli M, Iglesias JF. Influence of intravenous fentanyl compared with morphine on ticagrelor absorption and platelet inhibition in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: rationale and design of the PERSEUS randomized trial. Eur Heart J Cardiovasc Pharmacother. 2019 Jul 1;5(3):158-163. doi: 10.1093/ehjcvp/pvy031. |
| ID | Term |
|---|---|
| D005283 | Fentanyl |
| D009020 | Morphine |
| D000077486 | Ticagrelor |
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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