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.

Abstract

Aims: Recent evidence demonstrates that intravenous morphine significantly reduces absorption and delays onset of action of oral P2Y12 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 12 h post-loading dose. Pharmacodynamic assessments will include P2Y12 reaction units (PRU) measured by VerifyNow P2Y12. 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 (AUC0-t) for ticagrelor and AR-C124910XX. The primary endpoint is platelet reactivity assessed by PRU at 2 h 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.

Keywords: Fentanyl; Platelet inhibition; ST-segment elevation myocardial infarction; Ticagrelor.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Drug Interactions
  • Fentanyl / administration & dosage*
  • Fentanyl / adverse effects
  • Gastrointestinal Absorption / drug effects*
  • Humans
  • Morphine / administration & dosage*
  • Morphine / adverse effects
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / mortality
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / administration & dosage*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / pharmacokinetics
  • Randomized Controlled Trials as Topic
  • Receptors, Purinergic P2Y12 / blood
  • Receptors, Purinergic P2Y12 / drug effects
  • ST Elevation Myocardial Infarction / diagnosis
  • ST Elevation Myocardial Infarction / mortality
  • ST Elevation Myocardial Infarction / therapy*
  • Switzerland
  • Ticagrelor / administration & dosage*
  • Ticagrelor / adverse effects
  • Ticagrelor / pharmacokinetics
  • Treatment Outcome

Substances

  • Analgesics, Opioid
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Morphine
  • Ticagrelor
  • Fentanyl

Associated data

  • ClinicalTrials.gov/NCT02531165