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| ID | Type | Description | Link |
|---|---|---|---|
| ISSBRIL0067 |
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ticagrelor + ASA + Bivalirudin | Experimental | 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 | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ticagrelor + ASA + Bivalirudin | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Platelet-thrombus Formation in an ex Vivo Model of Thrombosis | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Platelet Reactivity | Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition | Pre-treatment baseline |
| Platelet Reactivity | Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Juan J Badimon, PhD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25104302 | Result | 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. |
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15 healthy volunteers recruited between July 2012 and March 2013
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| ID | Title | Description |
|---|---|---|
| FG000 | Ticagrelor, Then Clopidogrel | Acute antithrombotic effects of ticagrelor (180 mg + 90 mg) versus clopidogrel (600mg), when coadministered with aspirin (81mg) and bivalirudin (weight-adjusted clinical dose, given as bolus plus 1-hour infusion) with a 1-2 week washout period in between. |
| FG001 | Clopidogrel, Then Ticagrelor | Acute antithrombotic effects of ticagrelor (180 mg + 90 mg) versus clopidogrel (600mg), when coadministered with aspirin (81mg) and bivalirudin (weight-adjusted clinical dose, given as bolus plus 1-hour infusion) with a 1-2 week washout period in between. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (1 Day) |
| |||||||||||||
| Washout (1-2 Weeks) |
| |||||||||||||
| Second Intervention (1 Day) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Antithrombotic Effects | Acute antithrombotic effects of ticagrelor (180 mg + 90 mg) versus clopidogrel (600mg), when coadministered with aspirin (81mg) and bivalirudin (weight-adjusted clinical dose, given as bolus plus 1-hour infusion) using a randomized, two-treatment, two-period, cross-over design in healthy volunteers. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Platelet-thrombus Formation in an ex Vivo Model of Thrombosis | Change in thrombus size at 1 hour as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size. | Posted | Mean | 95% Confidence Interval | percent change | Pre-treatment baseline and 1 hour |
|
there were no adverse events
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ticagrelor, Then Clopidogrel | Acute antithrombotic effects of ticagrelor (180 mg + 90 mg) versus clopidogrel (600mg), when coadministered with aspirin (81mg) and bivalirudin (weight-adjusted clinical dose, given as bolus plus 1-hour infusion) with a 1-2 week wash out period in between. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Juan J. Badimon | Icahn School of Medicine at Mount Sinai | (212) 241-8484 | Juan.Badimon@mssm.edu |
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| ID | Term |
|---|---|
| D054058 | Acute Coronary Syndrome |
| D013927 | Thrombosis |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000077486 | Ticagrelor |
| C074619 | bivalirudin |
| D001241 | Aspirin |
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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|
| Clopidogrel + ASA + Bivalirudin | 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. |
|
|
| 1 hr post-treatment |
| Platelet Reactivity | Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition | 24-hours post-treatment |
| Blood Thrombogenicity | Coagulation times, assessed using the ROTEM thromboelastometry | Pre-treatment baseline |
| Blood Thrombogenicity | Coagulation times, assessed using the ROTEM thromboelastometry | 1 hr post-treatment |
| Blood Thrombogenicity | Coagulation times, assessed using the ROTEM thromboelastometry | 24-hours post-treatment |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Body mass index | Mean | Full Range | kg/m^2 |
|
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. 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. |
|
|
| Primary | Platelet-thrombus Formation in an ex Vivo Model of Thrombosis | Change in thrombus size at 24 hours as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size. | Posted | Mean | 95% Confidence Interval | percent change | Pre-treatment baseline and 24 hrs post treatment |
|
|
|
| Secondary | Platelet Reactivity | Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition | Posted | Number | 95% Confidence Interval | percent inhibition | Pre-treatment baseline |
|
|
|
| Secondary | Platelet Reactivity | Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition | Posted | Mean | 95% Confidence Interval | percent inhibition | 1 hr post-treatment |
|
|
|
| Secondary | Platelet Reactivity | Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition | Posted | Mean | 95% Confidence Interval | percent inhibition | 24-hours post-treatment |
|
|
|
| Secondary | Blood Thrombogenicity | Coagulation times, assessed using the ROTEM thromboelastometry | Posted | Mean | 95% Confidence Interval | seconds | Pre-treatment baseline |
|
|
|
| Secondary | Blood Thrombogenicity | Coagulation times, assessed using the ROTEM thromboelastometry | Posted | Mean | 95% Confidence Interval | seconds | 1 hr post-treatment |
|
|
|
| Secondary | Blood Thrombogenicity | Coagulation times, assessed using the ROTEM thromboelastometry | Posted | Mean | 95% Confidence Interval | seconds | 24-hours post-treatment |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Clopidogrel, Then Ticagrelor | Acute antithrombotic effects of ticagrelor (180 mg + 90 mg) versus clopidogrel (600mg), when coadministered with aspirin (81mg) and bivalirudin (weight-adjusted clinical dose, given as bolus plus 1-hour infusion) with a 1-2 week wash out period in between. | 0 | 15 | 0 | 15 |
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| D016769 |
| Embolism and Thrombosis |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |