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

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief 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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: Prasugrel; Drug: Ticagrelor	Not Applicable

Detailed 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.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	110 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A head-to Head Comparison of the Pharmacodynamic Effects of Prasugrel Compared With Ticagrelor in Patients With Coronary Artery Disease
Study Start Date :	January 2012
Actual Primary Completion Date :	June 2014
Actual Study Completion Date :	July 2014

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: Prasugrel; Prasugrel 60mg loading dose and 10 mg maintenance dose	Drug: Prasugrel; Prasugrel 60mg loading dose and 10mg maintenance dose; Other Name: Effient
Active Comparator: Ticagrelor; Ticagrelor 180mg loading dose and 90mg bid maintenance dose	Drug: Ticagrelor; Ticagrelor 180mg loading dose and 90mg bid maintenance dose; Other Name: Brillinta

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) [ Time Frame: 1 week ]
   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.

Secondary Outcome Measures :

1. Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) [ Time Frame: 2 hours ]
   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. Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) [ Time Frame: 24 hours ]
   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.

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 74 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209

Sponsors and Collaborators

University of Florida

Investigators

Principal Investigator:	Dominick Angiolillo, MD, PhD	University of Florida

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rollini F, Franchi F, Cho JR, DeGroat C, Bhatti M, Muniz-Lozano A, Singh K, Ferrante E, Wilson RE, Dunn EC, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ. A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study. Eur Heart J. 2016 Sep 14;37(35):2722-30. doi: 10.1093/eurheartj/ehv744. Epub 2016 Feb 3.

Responsible Party:	University of Florida
ClinicalTrials.gov Identifier:	NCT01852175 History of Changes
Other Study ID Numbers:	UFJ 2011-143
First Posted:	May 13, 2013
Results First Posted:	June 10, 2015
Last Update Posted:	June 10, 2015
Last Verified:	August 2014

Keywords provided by University of Florida:

Coronary artery disease; Dual antiplatelet therapy; prasugrel; ticagrelor

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Ticagrelor	Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Platelet Aggregation Inhibitors