Early Use of Rosuvastatin in Acute Coronary Syndromes: Targeting Platelet-Leukocyte Interactions

Study Overview
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Brief Summary
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The central hypothesis for this work is that platelet - leukocyte interactions play a critical role in the pathogenesis of acute ischemic events. The primary objective of the study is to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of acute coronary syndrome and percutaneous coronary intervention exerts beneficial vascular effects by reducing platelet - leukocyte interactions.

Official Title
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Early Use of Rosuvastatin (Crestor) in Acute Coronary Syndromes: Targeting Platelet-Leukocyte Interactions

Conditions
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Acute Coronary Syndrome, Angioplasty, Transluminal, Percutaneous Coronary, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Blood Platelets

Intervention / Treatment
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* Drug: rosuvastatin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be between 18 and 80 years old. Subjects must be willing and able to give informed consent A woman of child-bearing potential who is currently sexually active must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for up to 30 days after enrollment. Subjects must have symptoms of acute coronary syndrome as defined by 2 of the 3: (a) history of cardiac-ischemia-related symptoms of at least 10 minutes duration ≤ 8 hours prior to randomized treatment assignment (b) concurrent biomarker evidence of cardiac ischemia, as defined by troponin I or T greater that upper limit of normal (ULN) or creatine kinase-myocardial band (CK-MB) greater than ULN. (c) concurrent electrocardiographic evidence of cardiac ischemia, as defined by new of presumably new ST-segment depression (≥1 mm) or transient (<30 min) ST-segment elevation (≥ 1mm) in at least two contiguous leads. Subjects must be statin naive or currently only on low dose statin (Simvastatin 20mg, Pravastatin 40mg, or Atorvastatin 10mg) Exclusion Criteria: Age <18 years Age > 80 years Use of Crestor in the past 30 days GFR (estimated) <30 ml/min Hemodialysis History of liver failure Unexplained liver function abnormalities Current or planned use of cyclosporine or gemfibrozil Sepsis Hypotension Dehydration Trauma Severe metabolic, endocrine or electrolyte abnormality Recent (within the last 2 weeks) or planned (in the next month) major surgery HIV/AIDS with current of planned use of HIV protease inhibitors

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crestor<br> | Drug: rosuvastatin<br>* Patients (n = 54) presenting acute coronary syndrome/non-ST elevation myocardial infarction who present within 8 hours of symptom-onset will be randomized to two groups to receive rosuvastatin (40 mg oral dose) or placebo at the time of presentation, in addition to standard of care (aspirin, clopidogrel, low molecular weight heparin). Blood will be collected at baseline (time of enrollment, immediately prior to drug or placebo), at 6 - 8 hours, at 18 - 24 hours, and at 30 days for analysis of platelet - leukocyte co-aggregate formation, biomarkers of platelet - leukocyte interactions, and biomarkers of myocardial necrosis. Additional samples may be collected just after revascularization, in patients undergoing PCI. The group of patients treated with rosuvastatin will be maintained on rosuvastatin 20 mg daily and the group randomized to placebo will be given rosuvastatin (20 mg oral once daily) within 48 hoursof enrollment and after planned PCI, but before hospital discharge.<br>* Other names: crestor;|
| Placebo Comparator: sugar pill<br> | Drug: placebo<br>* frequency and duration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet - Leukocyte Aggregates | measured by flow cytometry | within first 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers of Platelet Function and Myocardial Necrosis |  | up to 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelet activation, platelet leukocyte aggregates