Clinical trial NCT02531165: Platelet Inhibition After Pre-hospital Ticagrelor Using Fentanyl Compared to Morphine in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myocardial Infarction
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2015-08-24
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU)
timeFrame: 2 hours after loading dose of Ticagrelor
Secondary outcomes:
measure: Residual PR by PRU
timeFrame: 0, 1, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor
measure: High on Treatment Platelet Reactivity (HTPR) rates
timeFrame: 0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor
measure: Peak plasma concentration (Cmax) of Ticagrelor and AR-C124910XX
timeFrame: at 1, 2, 4, 6 and 12 hours
measure: Time to peak plasma concentration (tmax) of Ticagrelor and AR-C124910XX
timeFrame: at 1, 2, 4, 6 and 12 hours
measure: Area under the plasma concentration-time curve of Ticagrelor
timeFrame: at 1, 2, 4, 6 and 12 hours
measure: Proportion of patients with 70% or greater resolution of the ST-segment elevation before PCI
timeFrame: at 2 hours
measure: Proportion of patients without Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography
timeFrame: at 2 hours
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
state: Vaud
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Juan F. Iglesias, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.