Comparing Ticagrelor Versus Clopidogrel on Microcirculation

Study Overview
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Brief Summary
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Recently, data (PLATO) from an AstraZeneca study of platelet inhibition and patient outcomes, a Phase III pivotal efficacy and safety study with a duration of up to 12 months comparing ticagrelor 90 mg twice daily dosing to clopidogrel 75 mg once daily dosing in acute coronary syndrome patients on ASA background, have demonstrated superiority of ticagrelor over clopidogrel in the prevention of fatal and non-fatal cardiovascular events. Currently, the mechanism for this mortality reduction remain uncertain. One hypothesis is a adenosine mediated theory that ticagrelor has been shown to enhance adenosine-induced vasodilation. Several experimental and clinical studies support the hypothesis that adenosine could reduce cardiac ischaemia reperfusion damage. Moreover, recent study has demonstrated that ticagrelor enhances adenosine-induced coronary vasodilatory responses in healthy humans. However, there are no available data on coronary circulation effects after chronic treatment of ticagrelor in patients with ACS who have altered resting coronary blood flow dynamics due to advanced coronary artery disease.

Detailed Description
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This study is a prospective, randomized, open-label, active controlled study with two parallel study groups. For inclusion in the study subjects should fulfill the following criteria: Provision of informed consent prior to any study specific procedures Female or male aged 20-85 years All patients with ACS scheduled for PCI will be eligible, assuming their ability to understand the character and individual consequences of participation as well as giving written informed consent. Be able to understand and comply with the requirements of the study, as judged by the investigator. To investigate the effects of ticagrelor on coronary microcirculation, IMR will be measured twice, 6 months apart in the same lesion, compared with clopidogrel. The IMR is defined as simultaneously measured distal coronary pressure divided by the inverse of the thermodilution-derived hyperaemic mean transit time (Tmn), or more simply, distal coronary pressure multiplied by the Tmn.

Official Title
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A Prospective Randomized Controlled Clinical Trial of Comparing ticagreLor Versus clopidogrEl on mIcrocirculation in Patients With Acute cOronary Syndrome Study

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures All patients with ACS scheduled for PCI will be eligible, assuming their ability to understand the character and individual consequences of participation as well as giving written informed consent. Be able to understand and comply with the requirements of the study, as judged by the investigator. Exclusion Criteria: History of intracranial bleeding Severe hepatic impairment Active pathologic bleeding Hypersensitivity to ticagrelor or any of the excipients Liver cirrhosis greater than or equal to Child class B Decreased serum platelet level (≤ 100,000/uL) Life expectancy ≤ 1 year Need for chronic oral anticoagulant therapy Patients with known bleeding diathesis or coagulation disorder History of previous intracranial bleed at any time, gastrointestinal bleed within the past 6 months, or major surgery within 30 days. Ischemic stroke within the previous 14 days Renal failure requiring dialysis or anticipated need for dialysis during the course of the study Concern for inability of the patient to comply with study procedures and/or follow up Unable to give informed consent.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor<br>Ticagrelor 90mg, twice a day | Drug: Ticagrelor<br>* 90mg, twice a day<br>|
| Active Comparator: Clopidogrel<br>Clopidogrel 75mg, once a day | Drug: Clopidogrel<br>* 75mg, once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Index of microcirculatory resistance using 0.014-in coronary pressure wire |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional flow reserve using 0.014-in coronary pressure wire |  | 6 months | 
| Coronary flow reserve using 0.014-in coronary pressure wire |  | 6 months |