High Ticagrelor Loading Dose in STEMI

NCT ID: NCT01898442

Last Updated: 2015-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2014-06-30

Brief 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.

Detailed 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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ticagrelor 180

Standard ticagrelor 180mg loading dose

Group Type: ACTIVE_COMPARATOR

Ticagrelor 180mg

Intervention Type: DRUG

Rndomization to standard or high ticagrelor loading dose regimens

Ticagrelor 270mg

High ticagrelor 270mg loading dose

Group Type: EXPERIMENTAL

Ticagrelor 270mg

Intervention Type: DRUG

Randomization to standard or high loading dose regimen

Ticagrelor 360mg

High ticagrelor 360mg loading dose

Group Type: EXPERIMENTAL

Ticagrelor 360mg

Intervention Type: DRUG

Randomization to standrad or high loading dose regimen

Interventions

Ticagrelor 180mg

Rndomization to standard or high ticagrelor loading dose regimens

Intervention Type: DRUG

Ticagrelor 270mg

Randomization to standard or high loading dose regimen

Intervention Type: DRUG

Ticagrelor 360mg

Randomization to standrad or high loading dose regimen

Intervention Type: DRUG

Other Intervention Names

Brilinta; Brilinta; Brilinta

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominick Angiolillo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Jacksonville, Florida, United States

Countries

United States

References

Franchi F, Rollini F, Cho JR, Bhatti M, DeGroat C, Ferrante E, Dunn EC, Nanavati A, Carraway E, Suryadevara S, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ. Impact of Escalating Loading Dose Regimens of Ticagrelor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results of a Prospective Randomized Pharmacokinetic and Pharmacodynamic Investigation. JACC Cardiovasc Interv. 2015 Sep;8(11):1457-1467. doi: 10.1016/j.jcin.2015.02.030.

Reference Type: DERIVED

PMID: 26404199 (View on PubMed)

Other Identifiers

TicagSTEMI

Identifier Type: -

Identifier Source: org_study_id