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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

July 1, 2013
June 16, 2014
September 2013
June 2014   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01898442 on ClinicalTrials.gov Archive Site
  • 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
Platelet function profiles [ Time Frame: 30 min and 1, 2, 4, 8, 24 hour ] [ Designated as safety issue: No ]
Mutiple parameters of platelet function at various time points including PRU assessed by VerifyNow and VASP
Not Provided
Not Provided
 
High Ticagrelor Loading Dose in STEMI
Pharmacodynamic Profiles of Ticagrelor in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Different Loading Dosage Regimens

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Coronary Artery Disease
  • 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
  • Drug: Ticagrelor 360mg
    Randomization to standrad or high loading dose regimen
    Other Name: Brilinta
  • Active Comparator: Ticagrelor 180
    Standard ticagrelor 180mg loading dose
    Interventions:
    • Drug: Ticagrelor 270mg
    • Drug: Ticagrelor 360mg
  • Experimental: Ticagrelor 270mg
    High ticagrelor 270mg loading dose
    Interventions:
    • Drug: Ticagrelor 180mg
    • Drug: Ticagrelor 360mg
  • Experimental: Ticagrelor 360mg
    High ticagrelor 360mg loading dose
    Interventions:
    • Drug: Ticagrelor 180mg
    • Drug: Ticagrelor 270mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
June 2014
June 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01898442
TicagSTEMI
Yes
University of Florida
University of Florida
Not Provided
Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida
University of Florida
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP