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High Ticagrelor Loading Dose in STEMI

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ClinicalTrials.gov Identifier: NCT01898442
Recruitment Status : Completed
First Posted : July 12, 2013
Results First Posted : June 8, 2015
Last Update Posted : June 8, 2015
Sponsor:
Information provided by (Responsible Party):
University of Florida

Study Description
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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.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Ticagrelor 180mg Drug: Ticagrelor 270mg Drug: Ticagrelor 360mg Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (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
Study Start Date : September 2013
Actual Primary Completion Date : June 2014
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Ticagrelor

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Ticagrelor 180
Standard ticagrelor 180mg loading dose
 Drug: Ticagrelor 180mg
Rndomization to standard or high ticagrelor loading dose regimens
Other Name: Brilinta
Experimental: Ticagrelor 270mg
High ticagrelor 270mg loading dose
 Drug: Ticagrelor 270mg
Randomization to standard or high loading dose regimen
Other Name: Brilinta
Experimental: Ticagrelor 360mg
High ticagrelor 360mg loading dose
 Drug: Ticagrelor 360mg
Randomization to standrad or high loading dose regimen
Other Name: Brilinta


Outcome Measures
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Primary Outcome Measures :
  1. Platelet Reactivity by VerifyNow P2Y12 [ Time Frame: 1 hour ]
    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


Secondary Outcome Measures :
  1. Platelet Reactivity by VerifyNow P2Y12 at Other Time Points [ Time Frame: 30 min and 2, 4, 8, 24 hours ]
    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

  2. Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points [ Time Frame: 30 min and 1, 2, 4, 8, 24 hours ]
    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

  3. Pharmacokinetic Profiles of Ticagrelor (Tmax) [ Time Frame: 24 hours ]
    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.

  4. Pharmacokinetic Profiles of Ticagrelor (Cmax) [ Time Frame: 24 hours ]
    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.

  5. Pharmacokinetic Profiles of Ticagrelor (AUC0-t) [ Time Frame: 24 hours ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01898442


Locations
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United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
Sponsors and Collaborators
University of Florida
Investigators
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Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01898442    
Other Study ID Numbers: TicagSTEMI
First Posted: July 12, 2013    Key Record Dates
Results First Posted: June 8, 2015
Last Update Posted: June 8, 2015
Last Verified: June 2014
Keywords provided by University of Florida:
platelet function
ticagrelor
STEMI
Additional relevant MeSH terms:
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Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
 Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs