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

• ClinicalTrials.gov Identifier: NCT02683707
• Recruitment Status: Completed
• First Posted: February 17, 2016
• Results First Posted: May 9, 2018
• Last Update Posted: June 7, 2018
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Other: Removal of Fentanyl from peri-procedural analgesia; Drug: Fentanyl; Drug: Lidocaine; Drug: Midazolam	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 212 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Platelet Aggregation After tiCagrelor Inhibition and FentanYl Trial
• Study Start Date: March 2016
• Actual Primary Completion Date: May 25, 2017
• Actual Study Completion Date: May 25, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: PCI without IV opiate; 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; Removal of Fentanyl from peri-procedural analgesia (which is otherwise routinely given for PCI); Drug: Lidocaine; Local Anesthetic; Drug: Midazolam; IV sedation
Active Comparator: PCI with IV opiate; IV midazolam and Local Anesthetic and IV fentanyl for peri-procedural analgesia	Drug: Fentanyl; IV peri-procedural analgesia; Drug: Lidocaine; Local Anesthetic; Drug: Midazolam; IV sedation

Outcome Measures

Primary Outcome Measures :

1. Ticagrelor Pharmacokinetics [ Time Frame: Measured over 24 hours (at 0, 0.5, 1, 2, 4, and 24 hours) ]
   Area under the curve for Ticagrelor Absorption

Secondary Outcome Measures :

1. Single Time-point Platelet Reactivity Using Verify Now [ Time Frame: Measured at 2 hours ]
   Blood test of Platelet Cell Reactivity using Verify Now (P2Y12 Reactivity Units)
2. Platelet Reactivity Using Light Transmission Aggregometry [ Time Frame: 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)
3. Patient Self-reported Pain [ Time Frame: 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".

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Hospital and University School of Medicicine

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: John W McEvoy, MBBCh MHS; Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] July 20, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02683707
• Other Study ID Numbers: IRB00089755
• First Posted: February 17, 2016
• Results First Posted: May 9, 2018
• Last Update Posted: June 7, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Johns Hopkins University:

Percutaneous Coronary Intervention; Blood Platelets; Fentanyl

Additional relevant MeSH terms:

Coronary Artery Disease; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Lidocaine; Fentanyl; Midazolam; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Analgesics, Opioid; Narcotics; Analgesics; Adjuvants, Anesthesia; Anesthetics, Intravenous; Anesthetics, General; Hypnotics and Sedatives; Anti-Anxiety Agents