SWAP-5: PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment

Sponsor
University of Florida (Other)
Overall Status
Completed
CT.gov ID
NCT04634162
Collaborator
Scott R. MacKenzie Foundation (Other)
22
1
2
9.7
2.3

Study Details

Study Description

Brief Summary

Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor ticagrelor is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. The methodological approach for this assessment should rely on comprehensive pharmacodynamics (PD) investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic (PK) investigations to assess systemic levels of the drug/drug metabolite, and mechanistic investigations by assessment of levels of P2Y12 receptor gene expression. The overarching aim of this investigation is to rule out a drug-drug interaction when ticagrelor is administered prior to cangrelor infusion.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor ticagrelor is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. In particular, ruling out a drug-drug interaction (DDI) is critical to this extent as the presence of a DDI would translate into reduced or abolished antiplatelet effects exposing these acute patients to an increased thrombotic risk. Despite the available evidence suggesting a lack of DDI with the use of ticagrelor in cangrelor treated patients, most data derive from studies in which ticagrelor was given at the time of initiation or during cangrelor infusion. To date, there is no data to fully rule out a DDI when ticagrelor is given prior to starting cangrelor infusion. The need for such investigation is underscored by the relatively high prevalence of pretreatment with ticagrelor in acute settings. The methodological approach for this assessment should rely on comprehensive pharmacodynamics (PD) investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic (PK) investigations to assess systemic levels of the drug/drug metabolite, and mechanistic investigations by assessment of levels of P2Y12 receptor gene expression. The overarching aim of this investigation is to rule out a DDI when ticagrelor is administered prior to cangrelor infusion.

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
The Switching Antiplatelet Therapy-5 (SWAP-5) study will be a prospective, randomized, double-blind, placebo controlled, cross-over PK and PD investigationThe Switching Antiplatelet Therapy-5 (SWAP-5) study will be a prospective, randomized, double-blind, placebo controlled, cross-over PK and PD investigation
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Patients, research staff and laboratory personnel will be blinded to treatment assignments. Masking and randomization of medications (cangrelor and placebo) will be performed by our institutional research pharmacy.
Primary Purpose:
Treatment
Official Title:
Pharmacodynamic and Pharmacokinetic Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment: The Switching Antiplatelet -5 (SWAP-5) Study
Actual Study Start Date :
Feb 9, 2021
Actual Primary Completion Date :
Aug 16, 2021
Actual Study Completion Date :
Nov 30, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cangrelor

Ticagrelor loading dose followed after 1 hour by cangrelor bolus and infusion

Drug: Cangrelor
Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase
Other Names:
  • Kengreal
  • Drug: Placebo
    Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase
    Other Names:
  • Normal saline
  • Placebo Comparator: Placebo

    Ticagrelor loading dose followed after 1 hour by placebo infusion

    Drug: Cangrelor
    Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase
    Other Names:
  • Kengreal
  • Drug: Placebo
    Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase
    Other Names:
  • Normal saline
  • Outcome Measures

    Primary Outcome Measures

    1. Platelet reactivity measured by VerifyNow [2 hours]

      The primary end point of the study will be the non-inferiority in P2Y12 reaction units (PRU) measured by VerifyNow after discontinuation of cangrelor vs. placebo

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion criteria:
    • Patients with known coronary artery disease (defined as prior type I myocardial infarction, coronary revascularization, percutaneous or surgical, or presence of at least a 50% stenosis in any major epicardial vessel).

    • Age > 18 years old

    • On aspirin 81mg/qd for at least 1 month

    Exclusion criteria:
    • Inability to provide written informed consent

    • Hemodynamic instability

    • On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 30 days

    • Known allergies to ticagrelor or cangrelor

    • Considered at high risk for bleeding

    • History of intracranial bleeding/hemorrhagic stroke

    • On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxoban) within past 30 days

    • Known platelet count <80x106/mL

    • Known hemoglobin <10 g/dL

    • Active bleeding

    • Known end stage renal disease on hemodialysis

    • Known severe hepatic dysfunction

    • Acute or severe bronchial asthma or upper airway obstruction.

    • Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.

    • Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.

    • Pregnant females [women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study]

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Florida Jacksonville Jacksonville Florida United States 32209

    Sponsors and Collaborators

    • University of Florida
    • Scott R. MacKenzie Foundation

    Investigators

    • Principal Investigator: Francesco Franchi, MD, University of Florida

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT04634162
    Other Study ID Numbers:
    • SMF-01
    First Posted:
    Nov 18, 2020
    Last Update Posted:
    Feb 7, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by University of Florida
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 7, 2022