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

NCT02012140 | Unknown Phase 4

• 1 other identifier: AZSC01
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Disease; Stable Angina; Myocardial Infarction; Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• 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).

Study Arms (1)

Ticagrelor

EXPERIMENTAL

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

Interventions

ticagrelor DRUG

Ticagrelor

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• LifeBridge Health: lead

Study Sites (1)

Sinai Center for Thrombosis Research

Baltimore, Maryland, 21215, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases; Angina, Stable; Myocardial Infarction; Coronary Artery Disease

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infarction; Ischemia; Pathologic Processes; Necrosis; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Paul Gurbel, MD

  Sinai Center for Thrombosis Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: November 5, 2013
• First Posted: December 16, 2013
• Study Start: January 1, 2014
• Primary Completion: January 1, 2015
• Last Updated: December 16, 2013

Record last verified: 2013-12

Locations

US (1)