Clinical trial NCT01706510: Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients
Official title: A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Clopidogrel
Ticagrelor
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Physiological Effects of Drugs
Lead sponsor: Rapid City Regional Hospital, Inc
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2012-10-15
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Assess the pharmacodynamic effect of ticagrelor vs. Clopidogrel in American Indian patients with stable coronary artery disease.

Detailed description: A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary Artery Disease

Eligibility criteria: Inclusion Criteria:

* Documented stable CAD fulfilling any of the following, and taking 81mg ASA daily treatment:
* Females must be post menopausal for at least one year or surgically sterile for at least 6 months and negative urine pregnancy test
* Self-identified as American Indian
* Genetic Inclusion Criteria: must sign the informed consent for genetic and biological sample banking.

Exclusion Criteria:

* Any indication for oral anticoagulant or dual antiplatelet treatment
* Concomitant therapy with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic index, or strong CYP3A inducers within 14 days and during study treatment and during:
* Increased bleeding risk including:
* Diabetic patients with HbAlC \> 10% at screening
* Contraindication to clopidogrel, ASA, or ticagrelor - A history of alcohol and/or substance abuse that could interfere with conduct of the trial
* Patients requiring dialysis
* Patients scheduled for revascularization (e.g., PCI, CABG) during the study period
* Any acute or chronic unstable condition in the past 30 days
* Known active or recurrent hepatic disorder
* Patients who had ACS or stent placed within 12 months of screening
* History of Uric Acid nephropathy

Primary outcomes:
measure: Compare ticagrelor's versus clopidogrel's inhibition of the P2Y12 receptor as measured by the decrease in P2Y12 Reaction Units (PRU) using VerifyNow TM.
timeFrame: At 2 hour time point after loading dose
Secondary outcomes:
measure: Compare the decrease of P2Y12 Reaction Units (PRU) by VerifyNow TM from ticagrelor and clopidogrel.
timeFrame: 0.5 and 8 hour time points after loading dose
measure: Compare the decrease in P2Y l2 Reaction Units (PRU) by VerifyNow™ from ticagrelor's and clopidogrel's morning dose on Day 7
timeFrame: At the 2, 8, and 24 hours after the last dose
measure: To evaluate and compare the pharmacodynamic effects, measured by the vasodilator-stimulated phosphoprotein (VASP) assay (platelet reactivity index [PRI]), in all subjects
timeFrame: Day1: pre-dose, 0.5, 2, and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours post final dose
measure: Assess and to compare the percentage of subjects with High on-treatment Platelet Reactivity (HPR) at all time points after randomized study treatment.
timeFrame: Day 1: Pre-dose, 0.5, 2 and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours after final dose
Other outcomes:
measure: CYP2C19 genotyping to identifying the wild-type CYP2C19 allele (*1), and characterize common alleles known to effect the metabolism of clopidogrel (*2, *3, *4,*5,*6,*7,*8 responsible for poor metabolism and *17 allele responsible for rapid metabolism).
timeFrame: One time-point
Locations:
city: Rapid City
country: United States
facility: Regional Heart Doctors/Black Hills Cardiovascular Research
state: South Dakota
Study officials:
affiliation: Rapid City Regional Hospital
name: James S Walder, MD
role: PRINCIPAL_INVESTIGATOR
References: