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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome; Angioplasty, Transluminal, Percutaneous Coronary; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Blood Platelets
• Intervention / Treatment: Drug: rosuvastatin; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Dept of Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must be between 18 and 80 years old.
2. Subjects must be willing and able to give informed consent
3. 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.
4. 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.
5. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: sugar pill	Drug: placebo; frequency and duration
EXPERIMENTAL: Crestor	Drug: rosuvastatin; 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.; Other Names: crestor

What is the study measuring?

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	Time Frame
Biomarkers of Platelet Function and Myocardial Necrosis	up to 30 days

Collaborators and Investigators

• Sponsor: Susan Smyth

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: November 12, 2010
• First Submitted That Met QC Criteria: November 15, 2010
• First Posted (ESTIMATE): November 16, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 28, 2017
• Last Update Submitted That Met QC Criteria: February 26, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Platelet activation; platelet leukocyte aggregates
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: 10-208-F1V