Clinical trial NCT01869309: Overcoming High On-Treatment Platelet Reactivity (HPR) During Prasugrel Therapy With Ticagrelor
Official title: Overcoming High On-Treatment Platelet Reactivity (HPR) During Prasugrel Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Coronary artery disease
anti-platelet medications
Platelet-aggregation Inhibitors
Lead sponsor: LifeBridge Health
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2013-06-05
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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%.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacodynamic (PD) Vasodilator Stimulated Phosphoprotein-Phosphorylation(VASP-P) in High On Prasugrel Platelet Reactivity(HPPR) stable CAD patients
timeFrame: 2 hours, 4 hours, and 14 days
Secondary outcomes:
measure: Prevalence of HPPR
timeFrame: 2 hours, 4 hours, and 14 days
measure: CYP2C19 relation to occurence of HPPR
timeFrame: 2 hours, 4 hours, and 14 days
measure: PD VerifyNow in HPPR stable CAD patients
timeFrame: 2 hour, 4 hour, 14 days
measure: PD LTA in HPPR stable CAD patients
timeFrame: 2 hours, 4 hours, 14 days
measure: Frequency of HPR
timeFrame: 2 hours, 4 hours, and 14 days
measure: PD effect(Prasugrel) relation to CYP2C19
timeFrame: 2 hours, 4 hours, and 14 days
Other outcomes:
measure: Number of Participants with Adverse Events
timeFrame: 14 days, 28 days
Locations:
city: Baltimore
country: United States
facility: Sinai Center for Thrombosis Research
state: Maryland
Study officials:
affiliation: LifeBridge Health
name: Paul A Gurbel, MD
role: PRINCIPAL_INVESTIGATOR
References: