High Ticagrelor Loading Dose in STEMI

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01898442
First received: July 1, 2013
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Drug: Ticagrelor 180mg
Drug: Ticagrelor 270mg
Drug: Ticagrelor 360mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacodynamic Profiles of Ticagrelor in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Different Loading Dosage Regimens

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Platelet reactivity [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
    The primary end-point of the study is the comparison of the PRU determined by VN-P2Y12 between 180 mg and 360 mg ticagrelor LD at 1 hour after administration


Secondary Outcome Measures:
  • Platelet function profiles by VerifyNow [ Time Frame: 30 min and 1, 2, 4, 8, 24 hour ] [ Designated as safety issue: No ]
    PRU levels assessed by VerifyNow

  • Platelet function profiles by VASP [ Time Frame: 30 min and 1, 2, 4, 8 and 24 hours ] [ Designated as safety issue: No ]
    PRI levels by VASP


Enrollment: 52
Study Start Date: September 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ticagrelor 180
Standard ticagrelor 180mg loading dose
Drug: Ticagrelor 270mg
Randomization to standard or high loading dose regimen
Other Name: Brilinta
Drug: Ticagrelor 360mg
Randomization to standrad or high loading dose regimen
Other Name: Brilinta
Experimental: Ticagrelor 270mg
High ticagrelor 270mg loading dose
Drug: Ticagrelor 180mg
Rndomization to standard or high ticagrelor loading dose regimens
Other Name: Brilinta
Drug: Ticagrelor 360mg
Randomization to standrad or high loading dose regimen
Other Name: Brilinta
Experimental: Ticagrelor 360mg
High ticagrelor 360mg loading dose
Drug: Ticagrelor 180mg
Rndomization to standard or high ticagrelor loading dose regimens
Other Name: Brilinta
Drug: Ticagrelor 270mg
Randomization to standard or high loading dose regimen
Other Name: Brilinta

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01898442

Locations
United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01898442     History of Changes
Other Study ID Numbers: TicagSTEMI
Study First Received: July 1, 2013
Last Updated: June 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
platelet function
ticagrelor
STEMI

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Myocardial Infarction
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014