Antithrombotic Effects of Ticagrelor Versus Clopidogrel

NCT ID: NCT01642238

Last Updated: 2016-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2013-04-30

Brief 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).

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.

Conditions

Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ticagrelor + ASA + Bivalirudin

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Clopidogrel + ASA + Bivalirudin

Intervention Type: DRUG

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.

Interventions

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 Type: 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.

Intervention Type: DRUG

Other Intervention Names

Brilinta (ticagrelor; Aspirin (ASA); Angiomax (bivalirudin); Plavix (clopidogrel); Aspirin (ASA); Angiomax (bivalirudin)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Juan J Badimon

OTHER

Sponsor Role: lead

Responsible Party

Juan J Badimon

Director, AtheroThrombosis Research Unit

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Juan J Badimon, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

References

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. No abstract available.

Reference Type: RESULT

PMID: 25104302 (View on PubMed)

Other Identifiers

ISSBRIL0067

Identifier Type: -

Identifier Source: secondary_id

GCO 12-0732

Identifier Type: -

Identifier Source: org_study_id