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

Coronary Artery Disease Clinical Trial

— SWAP-5  

Official title:

Pharmacodynamic and Pharmacokinetic Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment: The Switching Antiplatelet -5 (SWAP-5) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04634162
• Other study ID #: SMF-01
• Status: Completed
• Phase: Phase 4
• Start date: February 9, 2021
• Est. completion date: November 30, 2021

Study information

• Verified date: April 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: November 30, 2021
• Est. primary completion date: August 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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]

Related Conditions & MeSH terms

• Coronary Artery Disease

Intervention

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
• 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

Locations

Country	Name	City	State
United States	University of Florida Jacksonville	Jacksonville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	Scott R. MacKenzie Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet Reactivity Measured by VerifyNow	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	2 hours