Antithrombotic Effects of Ticagrelor Versus Clopidogrel

June 1, 2016 updated by: Juan J Badimon

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).

Study Overview

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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:
  • Aspirin (ASA)
  • Brilinta (ticagrelor
  • Angiomax (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.
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:
  • Aspirin (ASA)
  • Plavix (clopidogrel)
  • Angiomax (bivalirudin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
Time Frame: Pre-treatment baseline and 1 hour
Change in thrombus size at 1 hour as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
Pre-treatment baseline and 1 hour
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
Time Frame: Pre-treatment baseline and 24 hrs post treatment
Change in thrombus size at 24 hours as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
Pre-treatment baseline and 24 hrs post treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet Reactivity
Time Frame: Pre-treatment baseline
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
Pre-treatment baseline
Platelet Reactivity
Time Frame: 1 hr post-treatment
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
1 hr post-treatment
Platelet Reactivity
Time Frame: 24-hours post-treatment
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
24-hours post-treatment
Blood Thrombogenicity
Time Frame: Pre-treatment baseline
Coagulation times, assessed using the ROTEM thromboelastometry
Pre-treatment baseline
Blood Thrombogenicity
Time Frame: 1 hr post-treatment
Coagulation times, assessed using the ROTEM thromboelastometry
1 hr post-treatment
Blood Thrombogenicity
Time Frame: 24-hours post-treatment
Coagulation times, assessed using the ROTEM thromboelastometry
24-hours post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (ACTUAL)

March 1, 2013

Study Completion (ACTUAL)

April 1, 2013

Study Registration Dates

First Submitted

July 13, 2012

First Submitted That Met QC Criteria

July 13, 2012

First Posted (ESTIMATE)

July 17, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

July 11, 2016

Last Update Submitted That Met QC Criteria

June 1, 2016

Last Verified

June 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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