- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01642238
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10029
- Icahn School of Medicine at Mount Sinai
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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:
|
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:
|
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
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Acute Coronary Syndrome
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Purinergic P2Y Receptor Antagonists
- Purinergic P2 Receptor Antagonists
- Purinergic Antagonists
- Purinergic Agents
- Protease Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Aspirin
- Ticagrelor
- Clopidogrel
- Bivalirudin
- Hirudins
Other Study ID Numbers
- GCO 12-0732
- ISSBRIL0067
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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