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

Abstract

Aims Recent evidence demonstrates that intravenous morphine significantly reduces absorption and delays onset of action of oral P2Y(12) receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We aimed to assess the influence of intravenous fentanyl compared with morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients undergoing pPCI for STEMI. Methods and results Single-centre, prospective, open-label, randomized controlled study that will randomly assign in a 1:1 ratio patients with STEMI undergoing pPCI to receive intravenous fentanyl or morphine following a pre-hospital 180-mg loading dose of ticagrelor (ClinicalTrials.gov Identifier: NCT02531165). Pharmacokinetic and pharmacodynamic analyses will be performed at baseline and 1, 2, 4, 6, and 12h post-loading dose. Pharmacodynamic assessments will include P2Y(12) reaction units (PRU) measured by VerifyNow P2Y(12). Pharmacokinetic assessments include determination of maximal observed plasma concentrations, time for maximal plasma concentration, and area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC(0-t)) for ticagrelor and AR-C124910XX. The primary endpoint is platelet reactivity assessed by PRU at 2h post ticagrelor loading dose. Conclusion PERSEUS will provide randomized data regarding the impact of fentanyl administration, in patients with STEMI undergoing pPCI, on platelet inhibition and ticagrelor absorption and total exposure.