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

Coronary Artery Disease Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02012140
• Other study ID #: AZSC01
• Status: Not yet recruiting
• Phase: Phase 4
• First received: November 5, 2013
• Last updated: December 10, 2013
• Start date: January 2014

Study information

• Verified date: December 2013
• Source: LifeBridge Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina, Stable
• Cardiovascular Disease
• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Myocardial Infarction
• Myocardial Ischemia
• Stable Angina

Intervention

Drug:
• ticagrelor

Locations

Country	Name	City	State
United States	Sinai Center for Thrombosis Research	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
LifeBridge Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inhibition of platelet aggregation	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	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).	No