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Impact of Ticagrelor Re-load on Pharmacodynamic Profiles

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01731041
Recruitment Status : Completed
First Posted : November 21, 2012
Results First Posted : June 10, 2015
Last Update Posted : June 10, 2015
Information provided by (Responsible Party):
University of Florida

Brief Summary:
Platelets are parts of your blood that stick together to help form a clot. The stickier your platelets are, the greater your chance of having a heart attack. A clot in the wrong place can lead to a heart attack or stroke. Ticagrelor (Brilinta) keeps platelets from sticking together and it helps people from having a heart attack. The American College of Cardiology has recommended a combination of aspirin and Brilinta as one of the best treatments for the prevention of heart attacks, and death in patients who have had a heart attack or coronary stents. However, it is unknown if Brilinta may improve its work to keep platelets from sticking together giving a loading dose in patients already treated with Brilinta. A loading dose is a one-time increased dose of the same drug. The purpose of this study is to demonstrate whether the platelets of patients treated with Brilinta become less sticky when Brilinta is re-loaded.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Ticagrelor 180mg Drug: Ticagrelor 90mg Not Applicable

Detailed Description:
A higher degree of platelet inhibition remains the goal of peri-interventional and long-term anti-thrombotic therapy in patients with coronary artery disease. Previous observations have shown that in patients on clopidogrel therapy undergoing percutanoues coronary intervention who get re-loaded with clopidogrel obtain enhanced platelet inhibition. Ticagrelor represents a new class of nonthienopyridine platelet inhibitors designed to address the limitations of current oral antiplatelet therapy, which has been recently approved for clinical use. However, to date it is unknown if greater inhibition of platelet aggregation can be achieved by adding a ticagrelor loading dose in patients already on maintenance ticagrelor therapy (90 mg twice daily). In addition, how to manage patients undergoing coronary interventions already on chronic ticagrelor therapy with regards to ticagrelor loading is an emerging clinical question which has yet to be explored. Therefore, understanding the pharmacodynamic implications of a ticagrelor re-load strategy in patients on already on chronic ticagrelor therapy is warranted. The scope of the present study is to evaluate the impact of ticagrelor re-load in patients on chronic ticagrelor therapy. A total of 60 patients will be randomized into one of the following two arms of treatment: 1) 90 mg of ticagrelor; 2) 180 mg of ticagrelor. Pharmacodynamic assessments will be performed at baseline, 1-hour and 4-hour after dosing administration. Comparison between baseline and 4-hour values in term of platelet P2Y12 reactivity index determined by whole blood vasodilator-stimulated phosphoprotein will be the primary end-point of the study. Secondary endpoints will include other pharmacodynamic measures.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Impact of Ticagrelor Re-load on Pharmacodynamic Profiles in Patients on Maintenance Ticagrelor Therapy
Study Start Date : January 2013
Actual Primary Completion Date : June 2014
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Ticagrelor

Arm Intervention/treatment
Experimental: Ticagrelor 180mg
Patients randomized to this arm will be administered 180 mg of ticagrelor (experimental arm, loading dose).
Drug: Ticagrelor 180mg
Patients will receive 180 mg of ticagrelor
Other Name: Brilinta

Active Comparator: Ticagrelor 90mg
Patients randomized to this arm will be administered 90 mg dose of ticagrelor (active comparator, standard dose).
Drug: Ticagrelor 90mg
Patients will receive 90 mg of ticagrelor
Other Name: Brilinta

Primary Outcome Measures :
  1. Platelet Reactivity Index (PRI) by Vasodilator-stimulated Phosphoprotein (VASP) [ Time Frame: 4 hours ]
    The primary end-point of the study is the comparison in the platelet reactivity index (PRI%) determined by vasodilator-stimulated phosphoprotein (VASP) between baseline and 4-hour after dosing in each arm of treatment

Secondary Outcome Measures :
  1. P2Y12 Reaction Units (PRU) Determined by VerifyNow P2Y12 [ Time Frame: 4 hours ]
    Secondary analysis included the differences of platelet reactivity expressed as P2Y12 reaction units (PRU) in each group using the VerifyNow P2Y12 system.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with a clinical indication to be on ticagrelor therapy (90mg/bid)
  2. On treatment with ticagrelor 90mg twice daily for at least 14 days
  3. Age between 18 to 80 years
  4. On aspirin <100mg/day

Exclusion Criteria:

  1. History of intracranial bleeding
  2. Severe hepatic impairment (ALT >2.5 times the upper limit of normal)
  3. Active bleeding or propensity to bleed
  4. Recent antiplatelet treatment (< 14 days) with a glycoprotein IIb/IIIa antagonist

6. Platelet count <80x106/mL 7. Hemodynamic instability 8. Serum creatinine <30 mL/min 9. On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban) 10. Patients with sick sinus syndrome or II or III degree AV block without pacemaker protection 12. Drugs interfering CYP3A4 metabolism (to avoid interaction with Ticagrelor): ketoconazole, itraconazole, voriconazole, clarithromicin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromizycin 13. Hemoglobin < 10g/dL 14. Pregnant females [women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study].

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01731041

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United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
Sponsors and Collaborators
University of Florida
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Principal Investigator: Dominick J Angiolillo, MD, PhD University of Florida

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of Florida Identifier: NCT01731041    
Other Study ID Numbers: UFJ 2012-096
First Posted: November 21, 2012    Key Record Dates
Results First Posted: June 10, 2015
Last Update Posted: June 10, 2015
Last Verified: May 2015
Keywords provided by University of Florida:
coronary disease, platelet function, platelet inhibitors
Additional relevant MeSH terms:
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Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs