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Antithrombotic Effects of Ticagrelor Versus Clopidogrel

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Juan J Badimon, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01642238
First received: July 13, 2012
Last updated: March 19, 2013
Last verified: March 2013
History of Changes
  Purpose

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).


Condition Intervention Phase
Acute Coronary Syndrome
 Drug: Ticagrelor + ASA + Bivalirudin
Drug: Clopidogrel + ASA + Bivalirudin
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Crossover Study of the Antithrombotic Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin When Administered With Bivalirudin

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 thrombogenicity by Thromboelastography [ Time Frame: Pre-treatment baseline ] [ Designated as safety issue: No ]
  • Blood thrombogenicity by Thromboelastography [ Time Frame: 1 hr post-treatment ] [ Designated as safety issue: No ]
  • Blood thrombogenicity by Thromboelastography [ Time Frame: 24-hours post-treatment ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: July 2012
Estimated Study Completion Date: June 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ticagrelor + ASA + Bivalirudin 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 Name: Brilinta (ticagrelor), Aspirin (ASA) and Angiomax (bivalirudin)
Active Comparator: Clopidogrel + ASA + 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 Name: Plavix (clopidogrel), Aspirin (ASA) and Angiomax (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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01642238

Locations
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Juan J Badimon
AstraZeneca
Investigators
Principal Investigator: Juan J Badimon, PhD Icahn School of Medicine at Mount Sinai
  More Information

No publications provided

Responsible Party: Juan J Badimon, Director, AtheroThrombosis Research Unit, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01642238     History of Changes
Other Study ID Numbers: GCO 12-0732, ISSBRIL0067
Study First Received: July 13, 2012
Last Updated: March 19, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Antiplatelet
ticagrelor
clopidogrel
bivalirudin
thrombosis

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Aspirin
Ticlopidine
Hirudins
Clopidogrel
Bivalirudin
Ticagrelor
 Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents

ClinicalTrials.gov processed this record on June 17, 2013