Effect of intravenous fentanyl on ticagrelor absorption and platelet inhibition among patients undergoing percutaneous coronary intervention: Design, rationale, and sample characteristics of the PACIFY randomized trial

Contemp Clin Trials. 2018 Jan:64:8-12. doi: 10.1016/j.cct.2017.11.011. Epub 2017 Nov 21.

Abstract

Introduction: Morphine reduces and delays the absorption of oral P2Y12 platelet inhibitors. Fentanyl is another opiate often administered during percutaneous coronary interventions (PCI). The PACIFY study will test whether intravenous fentanyl also impairs the absorption and action of oral P2Y12 inhibitors.

Methods: PACIFY is a single-center trial randomizing adults undergoing clinically-indicated coronary angiography to have the procedure with or without fentanyl. All patients will receive local anesthetic and intravenous midazolam. Doses of all drugs are at the discretion of treating providers. Patients that require PCI receive 180mg of oral ticagrelor during the angiography procedure. The primary outcome is area under the ticagrelor plasma concentration-time curve. Secondary outcomes include platelet inhibition 2-h after loading, measured both by VerifyNow® (Accriva Diagnostics, San Diego, California) and by light-transmission platelet aggregometry. We will also survey patient comfort and measure high-sensitivity troponin levels. Patients and outcomes assessors are blinded, treating providers are not.

Results: A total of 212 patients are participating, 70 of whom required PCI. Baseline characteristics are numerically well balanced in both study arms. Mean age is 63years and 27% are female. There were no differences in total midazolam dose during the index PCI procedure, whereas mean total fentanyl dose was 9 mcg in the no-fentanyl arm (2 participants in this arm required fentanyl for bailout treatment of pain) versus 96 mcg in the fentanyl arm.

Conclusions: This study will provide important information on the impact of fentanyl administered during PCI on the absorption of ticagrelor and its antiplatelet activity.

Trial registration: clinicaltrials.gov Identifier: NCT02683707.

Keywords: Fentanyl; PCI; Pharmacodynamics; Pharmacokinetics; Platelet inhibition; Ticagrelor.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analgesics, Opioid / pharmacology*
  • Area Under Curve
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Fentanyl / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention / methods*
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Platelet Aggregation Inhibitors / pharmacology
  • Research Design
  • Ticagrelor / pharmacokinetics*
  • Ticagrelor / pharmacology

Substances

  • Analgesics, Opioid
  • Platelet Aggregation Inhibitors
  • Ticagrelor
  • Fentanyl

Associated data

  • ClinicalTrials.gov/NCT02683707