Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Stable Angina, NSTEMI and STEMI Undergoing PCI

Sponsor

LifeBridge Health (Other)

Overall Status

Unknown status

CT.gov ID

NCT02012140

Collaborator

(none)

200

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

Ticagrelor therapy has been shown to reduce the rates of cardiovascular events and all-cause mortality compared to clopidogrel therapy in patients with acute coronary syndromes (ACS). The benefit of this study would be to demonstrate that ticagrelor therapy is associated with equivalent platelet inhibition irrespective of the disease status in patients undergoing PCI.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease Stable Angina Myocardial Infarction Coronary Artery Disease	Drug: ticagrelor	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Jan 1, 2014

Anticipated Primary Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ticagrelor As per ACC/AHA and ESC guidelines 180 mg is the recommended LD. The ticagrelor 90 mg BID dose, following the loading dose, has been selected for the clopidogrel naïve patients with stable angina, NSTEMI and STEMI patients undergoing PCI as the maintenance dose for this study since it is the FDA recommended dose.	Drug: ticagrelor

Arm

Intervention/Treatment

Experimental: Ticagrelor

As per ACC/AHA and ESC guidelines 180 mg is the recommended LD. The ticagrelor 90 mg BID dose, following the loading dose, has been selected for the clopidogrel naïve patients with stable angina, NSTEMI and STEMI patients undergoing PCI as the maintenance dose for this study since it is the FDA recommended dose.

Drug: ticagrelor

Outcome Measures

Primary Outcome Measures

Inhibition of platelet aggregation [Pre-LD dose, 0.5, 1, 2, 3, 4-6, the next day just before and 1, 2 and 4 hours after morning maintenance dose and pre-dose and 1, 2 and 4 hours after the last study MD dose (14 +/- 3 days).]
The primary end point is the pharmacodynamic (inhibition of platelet aggregation, IPA) effect of 180mg LD ticagrelor measured at 1hour post-dose by 20uM ADP-induced maximum platelet aggregation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Stable Angina: Stable coronary artery disease patients with documented ischemia undergoing elective PCI will be enrolled.Inclusion criteria for enrollment in the ACS group with or without ST-segment elevation, requires onset of symptoms during the previous 48 hours.

NSTEMI

For patients who had an ACS without ST-segment elevation (NTSEMI), two of the following criteria had to be met:

a positive test of a biomarker (troponin I) in accordance with the universal definitions indicating myocardial necrosis
ST-segment changes on electrocardiography, indicating ischemia that do not meet criteria for STEMI.

STEMI

For patients who had an ACS with ST-segment elevation, the following two inclusion criteria had to be met:

either persistent ST-segment elevation of at least 0.1 mV in at least two contiguous leads or a new left bundle-branch block; and
the intention to perform primary PCI with 24 hours of symptom onset

Exclusion Criteria:

Patients who are on P2Y12 receptor blockers, oral anticoagulants, or GPIIb/IIIa receptor blocker therapies.
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)
History of refractory ventricular arrhythmias or 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)
History or evidence of congestive heart failure (New York Heart Association Class III or above ≤ 6 months before screening
Severe hepatic impairment defined as ALT> 2.5 X ULN
Uncontrolled hypertension, or systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg at screening
Severely impaired renal function (glomerular filtration rate < 30 mL/minute) or on dialysis
Platelet count <100 X103, illicit drug or alcohol abuse, prothrombin time>1.5 times control, haematocrit <30%, and creatinine >2.0 mg/dl.
Contraindication or other reason that ticagrelor should not be administered (eg, hypersensitivity, active bleeding, moderate or severe liver disease, history of previous intracranial bleed, GI bleed within the past 6 months, major surgery within 30 days)
Fibrinolytic therapy in the 24 hours prior to PCI, or planned fibrinolytic treatment following PCI.
Participation in another investigational drug or device study in the last 30 -Pregnancy or lactation
Concomitant oral or intravenous therapy (see examples below) with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers which cannot be stopped for the course of the study
Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir
Substrates with narrow therapeutic index: cyclosporine, quinidine
Strong inducers: rifampin/rifampicin, phenytoin, carbamazepine
Any other condition which in the opinion of the investigator, may either put the patient at risk or influence the result of the study (eg, cardiogenic shock or severe haemodynamic instability, active cancer, risk for non-compliance, risk for being lost to follow up)