Acute Coronary Syndrome, Angioplasty, Transluminal, Percutaneous Coronary, Blood Platelets, Hydroxymethylglutaryl-CoA Reductase Inhibitors
Conditions
Keywords
Platelet activation, platelet leukocyte aggregates
Brief summary
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.
Interventions
DRUGrosuvastatin
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.
DRUGplacebo
frequency and duration
Sponsors
Susan Smyth
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet - Leukocyte Aggregates | within first 24 hours | measured by flow cytometry |
Secondary
| Measure | Time frame |
|---|---|
| Biomarkers of Platelet Function and Myocardial Necrosis | up to 30 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects randomized to the placebo arm received a placebo dose at enrollment (day 1) and rosuvastatin 20mg for the next 30 days starting on day 2. | 26 |
| Rosuvastatin Subjects randomized to the rosuvastatin arm received rosuvastatin 40mg following enrollment (day 1) and rosustatin 20mg for the next 30 days starting at day 2. | 27 |
| Total | 53 |
Baseline characteristics
| Characteristic | Rosuvastatin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 10.4 | 56.0 years STANDARD_DEVIATION 10.7 | 54.5 years STANDARD_DEVIATION 10.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 47 Participants | 23 Participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 16 Participants | 33 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 26 | 1 / 27 |
| serious Total, serious adverse events | 2 / 26 | 1 / 27 |
Outcome results
Primary
Platelet - Leukocyte Aggregates
measured by flow cytometry
Time frame: within first 24 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Platelet - Leukocyte Aggregates | Baseline | 29.2 % leukocytes with platelets attached | Standard Error 3.8 |
| Placebo | Platelet - Leukocyte Aggregates | 8 Hour | 26.2 % leukocytes with platelets attached | Standard Error 4.2 |
| Placebo | Platelet - Leukocyte Aggregates | 24 Hour | 24.4 % leukocytes with platelets attached | Standard Error 4.2 |
| Rosuvastatin | Platelet - Leukocyte Aggregates | Baseline | 39.8 % leukocytes with platelets attached | Standard Error 4.9 |
| Rosuvastatin | Platelet - Leukocyte Aggregates | 8 Hour | 21.1 % leukocytes with platelets attached | Standard Error 3.2 |
| Rosuvastatin | Platelet - Leukocyte Aggregates | 24 Hour | 21.3 % leukocytes with platelets attached | Standard Error 2.8 |
Secondary
Biomarkers of Platelet Function and Myocardial Necrosis
Time frame: up to 30 days