High Ticagrelor Loading Dose in STEMI

University of Florida

Status and phase: Completed; Phase 2

Conditions: Coronary Artery Disease

Treatments: Drug: Ticagrelor 360mg; Drug: Ticagrelor 270mg; Drug: Ticagrelor 180mg

Study type: Interventional

Funder types: Other

Identifiers

NCT01898442

TicagSTEMI

Details and patient eligibility

About

Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients. However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects.

Full description

Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the cornerstone of treatment for prevention of thrombotic events in patients with acute coronary syndromes (ACS). Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events, including cardiovascular mortality. Ticagrelor was recently approved for clinical use in ACS patients, at a dose of 180 mg loading dose and 90 mg twice/day maintenance dose. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients, including those presenting with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). However, there are discordant data on the onset of its antiplatelet effects in this particular setting. In particular, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. However, if the administration of a higher ticagrelor loading dose may overcome this limitation is still unknown and represents the aim of our study. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects. This study will provide insights on the pharmacodynamic effects of higher ticagrelor loading doses and will help clinicians choose the most appropriate treatment to avoid complications related to inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary PCI.

Enrollment: 52 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with ST-elevation myocardial infarction undergoing primary PCI.
• Age between 18 and 80 years old.

Exclusion criteria

• History of prior intracranial bleeding.

• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 30 days.

• Known allergies to aspirin or ticagrelor.

• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).

• Treatment with IIb/IIIa glycoprotein inhibitors.

• Fibrinolytics within 24 hours

• Known blood dyscrasia or bleeding diathesis.

• Known platelet count <80x106/mL.

• Known hemoglobin <10 g/dL.

• Active bleeding.

• Hemodynamic instability.

• Known creatinine clearance <30 mL/minute.

• Known severe hepatic dysfunction.

• Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.

• Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.

• Pregnant females*.

  • Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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52 participants in 3 patient groups

Ticagrelor 180

Active Comparator group

Description:

Standard ticagrelor 180mg loading dose

Treatment:

Drug: Ticagrelor 180mg

Ticagrelor 270mg

Experimental group

Description:

High ticagrelor 270mg loading dose

Treatment:

Drug: Ticagrelor 270mg

Ticagrelor 360mg

Experimental group

Description:

High ticagrelor 360mg loading dose

Treatment:

Drug: Ticagrelor 360mg