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

NCT02683707 | Completed Phase 4 Results

• 1 other identifier: IRB00089755
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease

Keywords

Percutaneous Coronary Intervention; Blood Platelets; Fentanyl

Outcome Measures

Primary Outcomes (1)

• Ticagrelor Pharmacokinetics

  Area under the curve for Ticagrelor Absorption

  Measured over 24 hours (at 0, 0.5, 1, 2, 4, and 24 hours)

Secondary Outcomes (3)

• Single Time-point Platelet Reactivity Using Verify Now

  Measured at 2 hours

• Platelet Reactivity Using Light Transmission Aggregometry

  Measured at 2 hours

• Patient Self-reported Pain

  2 hours

Study Arms (2)

PCI without IV opiate

EXPERIMENTAL

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; Drug: Lidocaine; Drug: Midazolam

PCI with IV opiate

ACTIVE COMPARATOR

IV midazolam and Local Anesthetic and IV fentanyl for peri-procedural analgesia

Drug: Fentanyl; Drug: Lidocaine; Drug: Midazolam

Interventions

Removal of Fentanyl from peri-procedural analgesia OTHER

Removal of Fentanyl from peri-procedural analgesia (which is otherwise routinely given for PCI)

PCI without IV opiate

Fentanyl DRUG

IV peri-procedural analgesia

PCI with IV opiate

Lidocaine DRUG

Local Anesthetic

PCI with IV opiate; PCI without IV opiate

Midazolam DRUG

IV sedation

PCI with IV opiate; PCI without IV opiate

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Hospital and University School of Medicicine

Baltimore, Maryland, 21287, United States

Location

Related Publications (3)

• 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.

  PMID: 29972861 DERIVED

• 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.

  PMID: 29170073 DERIVED

• 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.

  PMID: 29046319 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Fentanyl; Lidocaine; Midazolam

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Small sample, surrogate endpoints

Results Point of Contact

• Title: Dr J William McEvoy
• Organization: JohnsHopkinsU

jmcevoy1@jhmi.edu

4109555000

Study Officials

• John W McEvoy, MBBCh MHS

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2016
• First Posted: February 17, 2016
• Study Start: March 1, 2016
• Primary Completion: May 25, 2017
• Study Completion: May 25, 2017
• Last Updated: June 7, 2018
• Results First Posted: May 9, 2018

Record last verified: 2018-05

Locations

US (1)