Clinical trial NCT02683707: The Platelet Aggregation After tiCagrelor Inhibition and FentanYl Trial (PACIFY)
Official title: The Platelet Aggregation After tiCagrelor Inhibition and FentanYl Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Percutaneous Coronary Intervention
Blood Platelets
Fentanyl
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2016-02-17
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Ticagrelor Pharmacokinetics
timeFrame: Measured over 24 hours (at 0, 0.5, 1, 2, 4, and 24 hours)
Secondary outcomes:
measure: Single Time-point Platelet Reactivity Using Verify Now
timeFrame: Measured at 2 hours
measure: Platelet Reactivity Using Light Transmission Aggregometry
timeFrame: Measured at 2 hours
measure: Patient Self-reported Pain
timeFrame: 2 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital and University School of Medicicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: John W McEvoy, MBBCh MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ibrahim K, Shah R, Goli RR, Kickler TS, Clarke WA, Hasan RK, Blumenthal RS, Thiemann DR, Resar JR, Schulman SP, McEvoy JW. Fentanyl Delays the Platelet Inhibition Effects of Oral Ticagrelor: Full Report of the PACIFY Randomized Clinical Trial. Thromb Haemost. 2018 Aug;118(8):1409-1418. doi: 10.1055/s-0038-1666862. Epub 2018 Jul 4.
citation: Ibrahim K, Goli RR, Shah R, Resar JR, Schulman SP, McEvoy JW. 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.
citation: McEvoy JW, Ibrahim K, Kickler TS, Clarke WA, Hasan RK, Czarny MJ, Keramati AR, Goli RR, Gratton TP, Brinker JA, Chacko M, Hwang CW, Johnston PV, Miller JM, Trost JC, Herzog WR, Blumenthal RS, Thiemann DR, Resar JR, Schulman SP. Effect of Intravenous Fentanyl on Ticagrelor Absorption and Platelet Inhibition Among Patients Undergoing Percutaneous Coronary Intervention: The PACIFY Randomized Clinical Trial (Platelet Aggregation With Ticagrelor Inhibition and Fentanyl). Circulation. 2018 Jan 16;137(3):307-309. doi: 10.1161/CIRCULATIONAHA.117.031678. Epub 2017 Oct 18. No abstract available.