Pharmacodynamic Effects of Prasugrel Compared With Ticagrelor in Patients With Coronary Artery Disease

Coronary Artery Disease Clinical Trial

Official title:

A head-to Head Comparison of the Pharmacodynamic Effects of Prasugrel Compared With Ticagrelor in Patients With Coronary Artery Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01852175
• Other study ID #: UFJ 2011-143
• Status: Completed
• Phase: N/A
• First received: May 8, 2013
• Last updated: May 26, 2015
• Start date: January 2012
• Est. completion date: July 2014

Study information

• Verified date: August 2014
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Recently, two P2Y12 receptor inhibitors have been approved for clinical use: prasugrel and ticagrelor. Both prasugrel and ticagrelor have shown to be associated with more potent antiplatelet effects compared with clopidogrel and are associated with an improved net clinical benefit. However, to date there are limited head-to-head comparisons of these two new agents.

Description:

Dual antiplatelet therapy consisting of aspirin and clopidogrel is the cornerstone of treatment for prevention of thrombotic events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, there are a considerable number of patients who continue to have recurrent ischemic events despite this treatment regimen. These observations underscore the need for more potent antiplatelet therapies. Recently, two P2Y12 receptor inhibitors have been approved for clinical use: prasugrel and ticagrelor. Both prasugrel and ticagrelor have shown to be associated with more potent antiplatelet effects compared with clopidogrel. These more favorable pharmacodynamic effects translate into reduced ischemic event rates, at the expense of an increased risk of bleeding in patients with acute coronary syndromes. Overall, these drugs are associated with an improved net clinical benefit. These findings from large-scale clinical investigations have led to approval of prasugrel and ticagrelor. However, to date there are limited head-to-head comparisons of these two new agents.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: July 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Patients with known coronary artery disease

• On maintenance treatment with aspirin (81 mg per day) and clopidogrel (75 mg per day) for at least 1-month as per standard of care.

• Age between 18 and 74 years old.

Exclusion Criteria:

• History of stroke, transient ischemic attack or intracranial bleeding.

• Known allergies to aspirin, prasugrel, ticagrelor, or clopidogrel.

• Weight <60kg

• On treatment with oral anticoagulation (coumarin derivate, dabigatran).

• Hemoglobin<10 gm/dL

• Platelet count <80x106/mL

• Active bleeding or hemodynamic instability.

• Creatinine Clearance <30 mL/minute.

• Baseline ALT >2.5 times the upper limit of normal.

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

• Drugs interfering with 2C19 metabolism (to avoid interaction with clopidogrel): , fluconazole (Diflucan), ketoconazole (Nizoral), voriconazole (VFEND), etravirine (Intelence), felbamate (Felbatol), fluoxetine (Prozac, Serafem, Symbyax), fluvoxamine (Luvox), and ticlopidine (Ticlid).

• Drugs interfering 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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Prasugrel
Prasugrel 60mg loading dose and 10mg maintenance dose
• Ticagrelor
Ticagrelor 180mg loading dose and 90mg bid maintenance dose

Locations

Country	Name	City	State
United States	University of Florida	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP)	The primary end-point of the study was the comparison in the platelet reactivity index (PRI%) determined by vasodilator-stimulated phosphoprotein (VASP) at 1 week between prasugrel and ticagrelor.	1 week	No
Secondary	Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)	A secondary outcome was the comparison between groups of platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein (VASP) at 2 hours after loading dose.	2 hours	No
Secondary	Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)	A secondary outcome was the comparison between groups of platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein (VASP) at 24 hours after loading dose.	24 hours	No