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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Susan Smyth, University of Kentucky
ClinicalTrials.gov Identifier:
NCT01241903
First received: November 12, 2010
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Acute Coronary Syndrome
Angioplasty, Transluminal, Percutaneous Coronary
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Blood Platelets
Drug: rosuvastatin
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Early Use of Rosuvastatin (Crestor) in Acute Coronary Syndromes: Targeting Platelet-Leukocyte Interactions

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Platelet - Leukocyte Aggregates [ Time Frame: within first 24 hours ] [ Designated as safety issue: No ]
    measured by flow cytometry


Secondary Outcome Measures:
  • Biomarkers of Platelet Function and Myocardial Necrosis [ Time Frame: up to 30 days ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: June 2011
Study Completion Date: February 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: crestor
Placebo Comparator: sugar pill Drug: placebo
frequency and duration

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241903

Locations
United States, Kentucky
University of Kentucky Dept of Cardiology
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
University of Kentucky
Investigators
Principal Investigator: Susan S Smyth, MD, PhD University of Kentucky
  More Information

No publications provided

Responsible Party: Susan Smyth, Principal investigator, University of Kentucky
ClinicalTrials.gov Identifier: NCT01241903     History of Changes
Other Study ID Numbers: 10-208-F1V
Study First Received: November 12, 2010
Results First Received: May 21, 2014
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Kentucky:
Platelet activation
platelet leukocyte aggregates

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014