The Platelet Aggregation After tiCagrelor Inhibition and FentanYl Trial (PACIFY)

Phase 4

Completed

Conditions: Coronary Artery Disease

Interventions: Drug: Fentanyl
Other: Removal of Fentanyl from peri-procedural analgesia
Drug: Lidocaine
Drug: Midazolam

Registration Number: NCT02683707

Lead Sponsor: Johns Hopkins University

Brief Summary: With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, opiates are the analgesic mainstay for acute coronary syndrome (ACS) patients reporting peri-procedural pain or nitrate-resistant chest pain. However, large observational studies suggest that opiate administration during ACS may result in adverse cardiovascular outcomes. Complimenting this, a number of recent mechanistic studies have demonstrated delayed and attenuated effects of oral dual anti-platelet therapy (DAPT) on platelet inhibition endpoints among subjects receiving intravenous morphine. These studies support the hypothesis that morphine delays the gastrointestinal absorption of DAPT medications. However, no data exist on the impact of intravenous fentanyl, a systemic opioid analgesic routinely administered during percutaneous coronary intervention (PCI) procedures, on the platelet inhibition effects of DAPT. The investigators hypothesize that, similar to morphine, fentanyl administered at the time of PCI will reduce and delay the effect of DAPT on platelet function. As such, the primary aim of this study is to test the impact of intravenous fentanyl on residual platelet reactivity by randomizing patients undergoing PCI to a strategy of peri-procedural benzodiazepine plus non-systemic local analgesia or to the current standard of benzodiazepine plus intravenous fentanyl. Given the critical need for rapid and robust inhibition of platelet function during PCI, this trial has true potential to change clinical practice, particularly if the investigators demonstrate reduced DAPT absorption and elevated residual platelet reactivity among patients receiving fentanyl during PCI.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 212

Inclusion Criteria

undergoing clinically indicated PCI; >18 years of age; able for PO medications and to provide informed consent

Exclusion Criteria

pregnant; any DAPT(clopidogrel, prasugrel, ticagrelor) within 14 days of enrollment; known coagulation disorders; active treatment with oral anticoagulant or low molecular weight heparin; impaired renal or hepatic function; platelets < 100 x10 3 /mcl; planned use of Glycoprotein 2b3a for PCI; Prior Trans Arterial Valve Replacement (TAVR) or planned TAVR post PCI; and contraindications to ticagrelor or opiates.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PCI with IV opiate	Fentanyl	IV midazolam and Local Anesthetic and IV fentanyl for peri-procedural analgesia
PCI with IV opiate	Lidocaine	IV midazolam and Local Anesthetic and IV fentanyl for peri-procedural analgesia
PCI with IV opiate	Midazolam	IV midazolam and Local Anesthetic and IV fentanyl for peri-procedural analgesia
PCI without IV opiate	Removal of Fentanyl from peri-procedural analgesia	IV midazolam and Local Anesthetic, with removal of IV fentanyl from peri-procedural analgesia (which is otherwise routinely given)
PCI without IV opiate	Lidocaine	IV midazolam and Local Anesthetic, with removal of IV fentanyl from peri-procedural analgesia (which is otherwise routinely given)
PCI without IV opiate	Midazolam	IV midazolam and Local Anesthetic, with removal of IV fentanyl from peri-procedural analgesia (which is otherwise routinely given)

Primary Outcome Measures

Name	Time	Method
Ticagrelor Pharmacokinetics	Measured over 24 hours (at 0, 0.5, 1, 2, 4, and 24 hours)	Area under the curve for Ticagrelor Absorption

Secondary Outcome Measures

Name	Time	Method
Single Time-point Platelet Reactivity Using Verify Now	Measured at 2 hours	Blood test of Platelet Cell Reactivity using Verify Now (P2Y12 Reactivity Units)
Platelet Reactivity Using Light Transmission Aggregometry	Measured at 2 hours	Blood test of Platelet Cell Reactivity using Light Transmission Aggregometry (reported as percent of baseline aggregation in response to adenosine diphosphate stimulation)
Patient Self-reported Pain	2 hours	Patient self report of pain using a visual analog scale (VAS). Scale ranges from 0 to 10 with 0 being "No pain" and 10 being "Most severe pain".