ACCEL-LOADING-ACS Study

Study Overview
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Brief Summary
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The purpose of this study is to determine whether adjunctive cilostazol loading/maintenance to standard treatment (aspirin, clopidogrel, and statin) is effective in reduction of major adverse cardiovascular events, platelet activation, inflammation and myonecrosis in patients with non-ST-elevation acute coronary syndrome (ACS)undergoing percutaneous coronary intervention (PCI).

Detailed Description
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In ACS patients, platelet activation, inflammation, and ischemia-reperfusion injury can be closely associated with the risk of post-PCI myonecrosis and ischemic events occurrence. In the ACCEL-AMI (Adjunctive Cilostazol versus high maintenance-dose ClopidogrEL in patients with Acute Myocardial Infarction)study, adjunctive cilostazol increased platelet inhibition compared with double-dose clopidogrel. Meanwhile, statins can reduce the extent of myonecrosis via limiting inflammation and myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K), ecto-5'-nucleotidase, Akt/endothelial nitric oxide synthase (eNOS), and the downstream effectors inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Inhibition of PI3K, adenosine receptors, eNOS, iNOS, or COX-2 abrogates the protective effects of statins. In animal study, the combination of low-dose statin with cilostazol synergistically limits infarct size. Multiple studies have shown that cilostazol can influence inflammation and RISK pathway using the similar pathway with statin. This study will be performed to evaluate the role of adjunctive cilostazol in platelet inhibition, inflammation, and myonecrosis compared with standard treatment.

Official Title
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ACCELerated Inhibition of Platelet Aggregation, Inflammation and Ischemia-reperfusion Injury by Adjunctive Cilostazol Loading in Patients With Acute Coronary Syndrome

Conditions
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Platelet Aggregation Inhibitors, Anti-inflammatory Agent, Myocardial Reperfusion Injury

Intervention / Treatment
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* Drug: Dual Anti-Platelet Therapy (DAPT)
* Drug: Triple Anti-Platelet Therapy (TAPT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at least 18 years of age Non-ST-elevation ACS patients undergoing PCI within 48 hours after hospitalization Exclusion Criteria: ST segment elevation acute myocardial infarction NSTE ACS with high-risk features warranting emergency coronary angiography Oral anticoagulation therapy with warfarin Use of pre-procedural glycoprotein IIb/IIIa inhibitor Contraindication to antiplatelet therapy AST or ALT ≥ 3 times upper normal Left ventricular ejection fraction < 30% WBC < 3,000/mm3, platelet < 100,000/mm3 Creatinine ≥ 3 mg/dl stroke within 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: DAPT<br> | Drug: Dual Anti-Platelet Therapy (DAPT)<br>* Loading: aspirin 300mg + clopidogrel 600mg Maintenance: aspirin 200mg/d + clopidogrel 75mg/d for 1 month<br>|
| Experimental: TAPT<br> | Drug: Triple Anti-Platelet Therapy (TAPT)<br>* Loading: cilostazol 200mg + aspirin 300mg + clopidogrel 600mg Maintenance: cilostazol 100mg bid+ aspirin 200mg/d+ clopidogrel 75mg/d for 1 month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiovascular events (MACE) | Composite of cardiac death, MI and ischemia-driven target lesion revascularization (TLR) | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P2Y12 reaction unit levels in the 2 arms |  | 1 month | 
| MACE incidence according to P2Y12 reaction unit |  | 1 month | 
| any post-procedural increase of markers of myocardial injury above ULN |  | 1 month | 
| post-procedural variations from baseline of hs-CRP levels in the 2 arms |  | 1 month | 
| ACUITY major/minor bleeding rate |  | 1 month | 
| 24hr post-procedural variations from baseline of inflammation markers (IL-6, TNF-alpha, cell adhesion molecules (VCAM, ICAM, E-selectin) |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cilostazol, Platelet, Inflammation, Myonecrosis