Impact of Ticagrelor Re-load on Pharmacodynamic Profiles
| Status: | Completed |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 5/5/2014 |
| Start Date: | January 2013 |
| End Date: | May 2014 |
| Contact: | Dominick Angiolillo, MD, PhD |
| Email: | dominick.angiolillo@jax.ufl.edu |
Impact of Ticagrelor Re-load on Pharmacodynamic Profiles in Patients on Maintenance Ticagrelor Therapy
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.
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.
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.
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.
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].
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