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

Study Overview
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Brief Summary
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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.

Official Title
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The Platelet Aggregation After tiCagrelor Inhibition and FentanYl Trial

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Other: Removal of Fentanyl from peri-procedural analgesia
* Drug: Fentanyl
* Drug: Lidocaine
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PCI without IV opiate<br>IV midazolam and Local Anesthetic, with removal of IV fentanyl from peri-procedural analgesia (which is otherwise routinely given) | Other: Removal of Fentanyl from peri-procedural analgesia<br>* Removal of Fentanyl from peri-procedural analgesia (which is otherwise routinely given for PCI)<br>Drug: Lidocaine<br>* Local Anesthetic<br>Drug: Midazolam<br>* IV sedation<br>|
| Active Comparator: PCI with IV opiate<br>IV midazolam and Local Anesthetic and IV fentanyl for peri-procedural analgesia | Drug: Fentanyl<br>* IV peri-procedural analgesia<br>Drug: Lidocaine<br>* Local Anesthetic<br>Drug: Midazolam<br>* IV sedation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ticagrelor Pharmacokinetics | Area under the curve for Ticagrelor Absorption | Measured over 24 hours (at 0, 0.5, 1, 2, 4, and 24 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Time-point Platelet Reactivity Using Verify Now | Blood test of Platelet Cell Reactivity using Verify Now (P2Y12 Reactivity Units) | Measured at 2 hours | 
| Platelet Reactivity Using Light Transmission Aggregometry | Blood test of Platelet Cell Reactivity using Light Transmission Aggregometry (reported as percent of baseline aggregation in response to adenosine diphosphate stimulation) | Measured at 2 hours | 
| Patient Self-reported Pain | 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. | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Percutaneous Coronary Intervention, Blood Platelets, Fentanyl