Impact of Ticagrelor Re-load on Pharmacodynamic Profiles

This study is currently recruiting participants.
Verified February 2014 by University of Florida
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01731041
First received: November 14, 2012
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

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 Intervention
Coronary Artery Disease
Drug: Ticagrelor re-load

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Impact of Ticagrelor Re-load on Pharmacodynamic Profiles in Patients on Maintenance Ticagrelor Therapy

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • platelet reactivity index (PRI) [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    The primary end-point is the comparison in the platelet reactivity index (PRI) determined by whole blood vasodilator-stimulated phosphoprotein (VASP) between baseline and 4-hour after dosing in each arms of treatment.


Secondary Outcome Measures:
  • Platelet reactivity [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    An exploratory analysis will be performed between the differences of platelet reactivity in each group using light transmittance aggregometry and point-of-care testing using the VerifyNow system.


Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ticagrelor 180mg
A total of 60 subjects will be included in this study and will be randomized in a prospective, double-blind fashion in two treatment groups: 1) 90 mg dose of ticagrelor (active comparator, standard dose); 2) 180 mg of ticagrelor (experimatal arm, loading dose).
Drug: Ticagrelor re-load
A total of 60 subjects will be included in this study and will be randomized in a prospective, double-blind fashion in two treatment groups: 1) 90 mg dose of ticagrelor (active comparator, standard dose); 2) 180 mg of ticagrelor (experimatal arm, loading dose).
Active Comparator: Ticagrelor 90mg
A total of 60 subjects will be included in this study and will be randomized in a prospective, double-blind fashion in two treatment groups: 1) 90 mg dose of ticagrelor (active comparator, standard dose); 2) 180 mg of ticagrelor (experimatal arm, loading dose).
Drug: Ticagrelor re-load
A total of 60 subjects will be included in this study and will be randomized in a prospective, double-blind fashion in two treatment groups: 1) 90 mg dose of ticagrelor (active comparator, standard dose); 2) 180 mg of ticagrelor (experimatal arm, loading dose).

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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].

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01731041

Contacts
Contact: Dominick Angiolillo, MD, PhD dominick.angiolillo@jax.ufl.edu

Locations
United States, Florida
University of Florida Recruiting
Jacksonville, Florida, United States, 32209
Contact: Dominick Angiolillo, MD, PhD       dominick.angiolillo@jax.ufl.edu   
Principal Investigator: Dominick Angiolillo, MD, PhD         
Sponsors and Collaborators
University of Florida
AstraZeneca
Investigators
Principal Investigator: Dominick J Angiolillo, MD, PhD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01731041     History of Changes
Other Study ID Numbers: UFJ 2012-096
Study First Received: November 14, 2012
Last Updated: February 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
coronary artery disease, platelet function, platelet inhibitors

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014