Coronary Artery Disease
Conditions
Keywords
Coronary artery disease, anti-platelet medications, Platelet-aggregation Inhibitors
Brief summary
The primary objective is to determine the pharmacodynamic effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable Coronary artery disease (CAD) patients who exhibit high-on prasugrel platelet reactivity defined as Vasodilator Stimulated Phosphoprotein-Phosphorylation (VASP-P) \>50%.
Interventions
DRUGPrasugrel
Patients will discontinue ticagrelor treatment and start 10 mg prasugrel daily while continuing 81 mg of aspirin daily.
DRUGTicagrelor
Patients will be given 180 mg of Ticagrelor followed by 90 mg twice a day while continuing 81 mg of aspirin daily).
Sponsors
AstraZeneca
LifeBridge Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female; age ≥ 18 and \< 75 years 2. Weight ≥ 60 kg 3. Currently on ASA therapy and eligible to reduce ASA dose to 81 mg daily if on higher dosing 4. On stable prasugrel maintenance dose for ≥1 month 5. Stable CAD patients defined as: subjects with documented evidence of a history of atherosclerotic coronary artery disease/surgical revascularization (defined as either a prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery). A minimum of 1 month must have elapsed between a subject's enrolment and any acute event, revascularization procedure or hospitalization for chest pain for that subject. 6. If female, may be enrolled if one of the following 3 criteria are met: 1)Had a hysterectomy or tubal ligation at least 6 months prior to signing ICF, 2)Post-menopausal for at least 1 year, 3)If of childbearing potential, will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner's use of condoms or partner's vasectomy. 7. Able and willing to provide written informed consent before entering the study
Exclusion criteria
1. Subject plans to undergo coronary revascularization at any time during the trial 2. Presence or history of any of the following: ischemic or hemorrhagic stroke; transient ischemic attack (TIA); intracranial neoplasm; arteriovenous malformation, or aneurysm; intracranial hemorrhage; head trauma (within 3 months of study entry) 3. History of refractory ventricular arrhythmias with an increased risk of bradycardic events (eg, subjects without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block or bradycardic-related syncope) 4. History or evidence of congestive heart failure (New York Heart Association Class III or above ≤ 6 months before screening 5. Severe hepatic impairment defined as ALT\> 2.5 X ULN 6. Uncontrolled hypertension, or systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg at screening 7. Severely impaired renal function (glomerular filtration rate \< 30 mL/minute) or on dialysis 8. Concomitant use with parenteral or oral anticoagulants 9. Platelet count \<100 X103
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic (PD) Vasodilator Stimulated Phosphoprotein-Phosphorylation(VASP-P) in High On Prasugrel Platelet Reactivity(HPPR) stable CAD patients | 2 hours, 4 hours, and 14 days | The primary objective is to determine the pharmacodynamic effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable CAD patients who exhibit high-on prasugrel platelet reactivity defined as VASP-P\>50%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of HPPR | 2 hours, 4 hours, and 14 days | Determine the prevalence of HPPR in a stable PCI population. |
| CYP2C19 relation to occurence of HPPR | 2 hours, 4 hours, and 14 days | Determine the relation of CYP2C19 activity to the occurrence of HPPR. |
| PD VerifyNow in HPPR stable CAD patients | 2 hour, 4 hour, 14 days | Evaluate the PD effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable CAD patients who exhibit HPPR defined as PRU \>208 by VerifyNow P2Y12 |
| Frequency of HPR | 2 hours, 4 hours, and 14 days | To determine the frequency of HPR after switching from ticagrelor to prasugrel after 14 days of treatment. |
| PD effect(Prasugrel) relation to CYP2C19 | 2 hours, 4 hours, and 14 days | To determine if the PD effect of prasugrel is related to the activity of CYP2C19 (phenotyping and genotyping) by measuring patients with and without HPPR. |
| PD LTA in HPPR stable CAD patients | 2 hours, 4 hours, 14 days | Evaluate the PD effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable CAD patients who exhibit HPPR based on light transmittance aggregometry (5 and 20 uM ADP, 4ug/mL Collagen) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events | 14 days, 28 days | To evaluate the safety and tolerability of switching subjects from Prasugrel to Ticagrelor and vice versa. |
Countries
United States
Contacts
Primary ContactKevin P Bliden, BS, MBA
Outcome results
None listed