Antithrombotic Effects of Ticagrelor Versus Clopidogrel

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Juan J Badimon, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:
NCT01642238
First received: July 13, 2012
Last updated: June 1, 2016
Last verified: June 2016

July 13, 2012
June 1, 2016
July 2012
March 2013   (final data collection date for primary outcome measure)
  • Platelet-thrombus Formation in an ex Vivo Model of Thrombosis [ Time Frame: Pre-treatment baseline and 1 hour ] [ Designated as safety issue: No ]
    Change in thrombus size at 1 hour as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
  • Platelet-thrombus Formation in an ex Vivo Model of Thrombosis [ Time Frame: Pre-treatment baseline and 24 hrs post treatment ] [ Designated as safety issue: No ]
    Change in thrombus size at 24 hours as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
  • Platelet-thrombus Formation in an ex Vivo Model of Thrombosis [ Time Frame: Pre-treatment baseline ] [ Designated as safety issue: No ]
  • Platelet-thrombus formation in an ex vivo model of thrombosis [ Time Frame: 1 hr post treatment ] [ Designated as safety issue: No ]
  • Platelet-thrombus Formation in an ex Vivo Model of Thrombosis [ Time Frame: 24 hrs post treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01642238 on ClinicalTrials.gov Archive Site
  • Platelet Reactivity [ Time Frame: Pre-treatment baseline ] [ Designated as safety issue: No ]
    Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
  • Platelet Reactivity [ Time Frame: 1 hr post-treatment ] [ Designated as safety issue: No ]
    Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
  • Platelet Reactivity [ Time Frame: 24-hours post-treatment ] [ Designated as safety issue: No ]
    Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
  • Blood Thrombogenicity [ Time Frame: Pre-treatment baseline ] [ Designated as safety issue: No ]
    Coagulation times, assessed using the ROTEM thromboelastometry
  • Blood Thrombogenicity [ Time Frame: 1 hr post-treatment ] [ Designated as safety issue: No ]
    Coagulation times, assessed using the ROTEM thromboelastometry
  • Blood Thrombogenicity [ Time Frame: 24-hours post-treatment ] [ Designated as safety issue: No ]
    Coagulation times, assessed using the ROTEM thromboelastometry
  • Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer [ Time Frame: Pre-treatment baseline ] [ Designated as safety issue: No ]
  • Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer [ Time Frame: 1 hr post-treatment ] [ Designated as safety issue: No ]
  • Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer [ Time Frame: 24-hours post-treatment ] [ Designated as safety issue: No ]
  • Blood thrombogenecity by Thromboelastography [ Time Frame: Pre-treatment baseline ] [ Designated as safety issue: No ]
  • Blood thrombogenecity by Thromboelastography [ Time Frame: 1 hr post-treatment ] [ Designated as safety issue: No ]
  • Blood thrombogenecity by Thromboelastography [ Time Frame: 24-hours post-treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Antithrombotic Effects of Ticagrelor Versus Clopidogrel
Randomized, Crossover Study of the Antithrombotic Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin When Administered With Bivalirudin
The purpose of this study is to determine whether treatment with ticagrelor (plus aspirin and bivalirudin) is more effective than treatment with clopidogrel (plus aspirin and bivalirudin).

The HORIZONS-AMI Trial compared the effectiveness of heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin in acute myocardial infarction (AMI) patients undergoing stent deployment 1. Overall the data showed benefits associated with the bivalirudin treatment with lower rates of all-cause mortality, cardiac mortality, re-infarction and non-CABG related major bleeding; However, the data seems to indicate a non-significant increase in acute stent thrombosis in the bivalirudin group. This observation seems to suggest the potential benefits of adding an antiplatelet agent to bivalirudin. A study by Dangas G et al found that in the HORIZONS-AMI patients, the group receiving 600 mg loading-dose of clopidogrel had significantly lower 30-day unadjusted rates of mortality, reinfarction and stent thrombosis than the 300 mg loading-dose group, without increase in bleeding rate. Furthermore, even though the benefits of bivalirudin were independent of the clopidogrel loading dose; the 600mg LD was associated with more benefits with both anticoagulation regimens. Similar observations have been reported in the ARMYDA-6 MI study.

It is our hypothesis that using ticagrelor instead of clopidogrel, given its more potent and faster activity, would have greater antithrombotic activity and therefore may reduce the rate of acute stent thrombosis when administered in combination with bivalirudin + ASA in AMI patients. To investigate this hypothesis, we will compare the antithrombotic effects of ticagrelor with clopidogrel, when administered in combination with ASA and bivalirudin, in healthy human volunteers using a cross-over study design. The antithrombotic activity will be assessed pre-treatment and 2-hours and 24-hours post treatment, using methodologies including Badimon Perfusion chamber, VerifyNow P2Y12 assay, platelet aggregation with Multiplate Analyzer and Thromboelastography.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Coronary Syndrome
  • Drug: Ticagrelor + ASA + Bivalirudin
    Single loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
    Other Names:
    • Brilinta (ticagrelor
    • Aspirin (ASA)
    • Angiomax (bivalirudin)
  • Drug: Clopidogrel + ASA + Bivalirudin
    Single loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
    Other Names:
    • Plavix (clopidogrel)
    • Aspirin (ASA)
    • Angiomax (bivalirudin)
  • Experimental: Ticagrelor + ASA + Bivalirudin
    Single loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
    Intervention: Drug: Ticagrelor + ASA + Bivalirudin
  • Active Comparator: Clopidogrel + ASA + Bivalirudin
    Single loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
    Intervention: Drug: Clopidogrel + ASA + Bivalirudin
Zafar MU, Vorchheimer DA, Tewar MP, Giannarelli C, Crippa M, Sartori S, Rodriguez D, Baber U, Mehran R, Badimon JJ. Ticagrelor reduces thrombus formation more than clopidogrel, even when co-administered with bivalirudin. Thromb Haemost. 2014 Nov;112(5):1069-70. doi: 10.1160/TH14-03-0269. Epub 2014 Aug 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
April 2013
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female volunteers between 18 and 65 years old.
  • Body mass index (BMI) 18 - 30 kg/m2 inclusive.
  • Healthy as assessed by a detailed medical history and physical examination.
  • Laboratory est results within the normal range.
  • Ability to provide signed informed consent.

Exclusion Criteria:

  • History of clinically relevant disease, bleeding, acute infectious disease or signs of acute illness.
  • Allergy or hypersensitivity to aspirin or thienopyridines, or atopy diagnosed by a physician.
  • Use of medication within one month prior to study drug administration.
  • History of drug abuse or alcohol consumption >20 g/day.
  • Inability to abstain from intensive muscular effort or sport competition.
  • Loss of >400 mL blood or blood donation within 3 months.
  • Positive serology for hepatitis B (HBs Ag) or hepatitis C.
  • Conditions associated with hemorrhagic risk.
  • Positive pregnancy test.
Both
18 Years to 65 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01642238
GCO 12-0732, ISSBRIL0067
No
Not Provided
Not Provided
Juan J Badimon, Icahn School of Medicine at Mount Sinai
Juan J Badimon
AstraZeneca
Principal Investigator: Juan J Badimon, PhD Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
June 2016

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