Antithrombotic Effects of Ticagrelor Versus Clopidogrel

Acute Coronary Syndrome Clinical Trial

Official title:

Randomized, Crossover Study of the Antithrombotic Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin When Administered With Bivalirudin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01642238
• Other study ID #: GCO 12-0732
• Secondary ID: ISSBRIL0067
• Status: Completed
• Phase: Phase 4
• First received: July 13, 2012
• Last updated: January 16, 2014
• Start date: July 2012
• Est. completion date: April 2013

Study information

• Verified date: January 2014
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Juan J Badimon	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet-thrombus formation in an ex vivo model of thrombosis		Pre-treatment baseline	No
Primary	Platelet-thrombus formation in an ex vivo model of thrombosis		1 hr post treatment	No
Primary	Platelet-thrombus formation in an ex vivo model of thrombosis		24 hrs post treatment	No
Secondary	Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer		Pre-treatment baseline	No
Secondary	Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer		1 hr post-treatment	No
Secondary	Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer		24-hours post-treatment	No
Secondary	Blood thrombogenicity by Thromboelastography		Pre-treatment baseline	No
Secondary	Blood thrombogenicity by Thromboelastography		1 hr post-treatment	No
Secondary	Blood thrombogenicity by Thromboelastography		24-hours post-treatment	No