High Ticagrelor Loading Dose in STEMI

Coronary Artery Disease Clinical Trial

Official title:

Pharmacodynamic Profiles of Ticagrelor in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Different Loading Dosage Regimens

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01898442
• Other study ID #: TicagSTEMI
• Status: Completed
• Phase: Phase 2
• First received: July 1, 2013
• Last updated: May 26, 2015
• Start date: September 2013
• Est. completion date: June 2014

Study information

• Verified date: June 2014
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Ticagrelor 180mg
Rndomization to standard or high ticagrelor loading dose regimens
• Ticagrelor 270mg
Randomization to standard or high loading dose regimen
• Ticagrelor 360mg
Randomization to standrad or high loading dose regimen

Locations

Country	Name	City	State
United States	University of Florida	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet Reactivity by VerifyNow P2Y12	The primary end-point of the study was the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 1 hour after administration	1 hour	No
Secondary	Platelet Reactivity by VerifyNow P2Y12 at Other Time Points	Secondary outcomes included the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 30 min and 2, 4, 8, 24 hours after ticagrelor loading dose administration	30 min and 2, 4, 8, 24 hours	No
Secondary	Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points	Secondary outcomes included the comparison of the platelet reactivity index (PRI) determined by vasodilator-stimulated phosphoprotein (VASP) at 30 min and 1, 2, 4, 8, 24 hours after ticagrelor loading dose administration	30 min and 1, 2, 4, 8, 24 hours	No
Secondary	Pharmacokinetic Profiles of Ticagrelor (Tmax)	Pharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.	24 hours	No
Secondary	Pharmacokinetic Profiles of Ticagrelor (Cmax)	Pharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.	24 hours	No
Secondary	Pharmacokinetic Profiles of Ticagrelor (AUC0-t)	Pharmacokinetic assessments included determination of plasma concentration of ticagrelor. Time for the maximum plasma concentration (Tmax), maximum observed plasma concentration (Cmax) and the area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) were calculated.	24 hours	No