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Impact of Ticagrelor Re-load on Pharmacodynamic Profiles

Primary Purpose

Coronary Artery Disease

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ticagrelor 180mg
Ticagrelor 90mg
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring coronary disease, platelet function, platelet inhibitors

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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].

Sites / Locations

  • University of Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ticagrelor 180mg

Ticagrelor 90mg

Arm Description

Patients randomized to this arm will be administered 180 mg of ticagrelor (experimental arm, loading dose).

Patients randomized to this arm will be administered 90 mg dose of ticagrelor (active comparator, standard dose).

Outcomes

Primary Outcome Measures

Platelet Reactivity Index (PRI) by Vasodilator-stimulated Phosphoprotein (VASP)
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

P2Y12 Reaction Units (PRU) Determined by VerifyNow P2Y12
Secondary analysis included the differences of platelet reactivity expressed as P2Y12 reaction units (PRU) in each group using the VerifyNow P2Y12 system.

Full Information

First Posted
November 14, 2012
Last Updated
May 26, 2015
Sponsor
University of Florida
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT01731041
Brief Title
Impact of Ticagrelor Re-load on Pharmacodynamic Profiles
Official Title
Impact of Ticagrelor Re-load on Pharmacodynamic Profiles in Patients on Maintenance Ticagrelor Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
coronary disease, platelet function, platelet inhibitors

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ticagrelor 180mg
Arm Type
Experimental
Arm Description
Patients randomized to this arm will be administered 180 mg of ticagrelor (experimental arm, loading dose).
Arm Title
Ticagrelor 90mg
Arm Type
Active Comparator
Arm Description
Patients randomized to this arm will be administered 90 mg dose of ticagrelor (active comparator, standard dose).
Intervention Type
Drug
Intervention Name(s)
Ticagrelor 180mg
Other Intervention Name(s)
Brilinta
Intervention Description
Patients will receive 180 mg of ticagrelor
Intervention Type
Drug
Intervention Name(s)
Ticagrelor 90mg
Other Intervention Name(s)
Brilinta
Intervention Description
Patients will receive 90 mg of ticagrelor
Primary Outcome Measure Information:
Title
Platelet Reactivity Index (PRI) by Vasodilator-stimulated Phosphoprotein (VASP)
Description
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
Time Frame
4 hours
Secondary Outcome Measure Information:
Title
P2Y12 Reaction Units (PRU) Determined by VerifyNow P2Y12
Description
Secondary analysis included the differences of platelet reactivity expressed as P2Y12 reaction units (PRU) in each group using the VerifyNow P2Y12 system.
Time Frame
4 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with a clinical indication to be on ticagrelor therapy (90mg/bid) On treatment with ticagrelor 90mg twice daily for at least 14 days Age between 18 to 80 years On aspirin <100mg/day Exclusion Criteria: History of intracranial bleeding Severe hepatic impairment (ALT >2.5 times the upper limit of normal) Active bleeding or propensity to bleed 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].
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dominick J Angiolillo, MD, PhD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26117466
Citation
Cho JR, Rollini F, Franchi F, DeGroat C, Bhatti M, Dunn EC, Ferrante E, Muniz-Lozano A, Suryadevara S, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ. Pharmacodynamic Effects of Ticagrelor Dosing Regimens in Patients on Maintenance Ticagrelor Therapy: Results From a Prospective, Randomized, Double-Blind Investigation. JACC Cardiovasc Interv. 2015 Jul;8(8):1075-1083. doi: 10.1016/j.jcin.2015.02.022. Epub 2015 Jun 24.
Results Reference
derived

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Impact of Ticagrelor Re-load on Pharmacodynamic Profiles

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