Pharmacodynamic Effects of Prasugrel Compared With Ticagrelor in Patients With Coronary Artery Disease - Full Text View

Purpose

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	Intervention
Coronary Artery Disease	Drug: Prasugrel Drug: Ticagrelor


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Single Blind (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

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease

Drug Information available for: Prasugrel Ticagrelor

U.S. FDA Resources

Further study details as provided by University of Florida:

Primary Outcome Measures:

Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) [ Time Frame: 1 week ] [ Designated as safety issue: No ]
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:

Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
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.
Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
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.


Enrollment:	110
Study Start Date:	January 2012
Study Completion Date:	July 2014
Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years to 74 Years (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01852175

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


Responsible Party:	University of Florida
ClinicalTrials.gov Identifier:	NCT01852175 History of Changes
Other Study ID Numbers:	UFJ 2011-143
Study First Received:	May 8, 2013
Results First Received:	May 4, 2015
Last Updated:	May 26, 2015
Health Authority:	United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on September 28, 2016