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

• Status: Recruiting
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Florida
• Collaborators: Scott R MacKenzie Foundation; Scott R. MacKenzie Foundation
• Treatments: Cangrelor

Criteria

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]