The use of acetylsalicylic acid in the primary prevention of cardiovascular events has been extensively studied but to a lesser extent in patients with moderate levels of cardiovascular risk. The current study is designed to prove the efficacy and tolerability of 100 mg enteric-coated Aspirin versus placebo in the prevention of cardiovascular disease (CVD) events, which include fatal and nonfatal myocardial infarction, fatal and nonfatal stroke and CV death, in a population with no history of known CVD who are at moderate risk of major CHD events (approximately 10-20% 10 year CHD risk). This corresponds to a patient population mean 10-year CVD risk of approximately 30%. Subjects are treated in a standard care setting and may receive treatment for the underlying risk factors as defined by the treating physician. Outcome events will be adjudicated by an Endpoint Adjudication Committee and the study will be monitored by an independent Data Safety Monitoring Board.
Summary of substantial Protocol amendments Amendment #2 from 09-APR-2008: * Systolic blood pressure (SBP) limit of 170 mmHg has been added to the exclusion criteria * Exclusion of patients currently taking anticoagulant medication * A longer interval between the daily dose of study drug and ibuprofen * Revised wording in moderate risk definitions for coronary heart disease (CHD) and cerebrovascular disease (CVD): "To evaluate the clinical effects of a 100 mg/day enteric-coated acetylsalicylic acid versus placebo in the reduction of CVD events in patients at moderate risk of major CHD events (approximately 10 to 20% 10-year CHD risk; approximately 20 to 30% 10-year risk of CVD). This corresponds to a patient population mean 10-year CVD risk of approximately 30%." Amendment #3 from 02-JAN-2009 • Increase in the number of allowed risk factors for males, age is no longer a risk factor Amendment #4 from 02-OCT-2013 * The primary endpoint is changed to include confirmed UA and TIA. * The estimated event rate is changed to 1.5% per year due to new information. * Effect size (risk reduction) changed from 14.9% to 17 to 18%. * Achieving 60,000 person-years instead of 1488 primary endpoint events * Additional treatment and follow-up for a maximum of another 12 months. * Change to reduced adverse event and concomitant therapy reporting
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
12,546
100mg enteric coated Aspirin, taken daily
Placebo, taken daily
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Graysville, Alabama, United States
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Pell City, Alabama, United States
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Phoenix, Arizona, United States
Unnamed facility
Scottsdale, Arizona, United States
Unnamed facility
Time to the First Occurrence of the Composite Outcome of MI (Myocardial Infarction), Stroke, Cardiovascular Death, UA (Unstable Angina) or TIA (Transient Ischemic Attack)
The primary efficacy endpoint was a composite outcome consisting of the first occurrence of confirmed MI, stroke, cardiovascular death, UA, TIA. The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses.
Time frame: Until follow-up (approximate 6 years)
Time to the First Occurrence of the Composite Outcome of Cardiovascular Death, MI, or Stroke (Ischemic, Hemorrhagic, or Unknown)
The time to Composite outcome consisting of the first occurrence of cardiovascular death, MI, or stroke (ischemic, hemorrhagic, or unknown) was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses.
Time frame: Until follow-up (approximate 6 years)
Time to the First Occurrence of the Individual Components of the Primary: Non-fatal MI, Total MI, Non-fatal Stroke, Total Stroke, Cardiovascular Death, UA and TIA
The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses.
Time frame: Until follow-up (approximately 6 years)
Time to All-cause Mortality, the First Occurrence of All Cancers Excluding Non-melanoma Skin Cancer (NMSC) and the First Occurrence of Colon Cancer
The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses.
Time frame: Until follow-up (approximately 6 years)
Incidence of All-cause Mortality, All Cancers Excluding Non-melanoma Skin Cancer and Colon Cancer
Time frame: Until follow-up (approximately 6 years)
Incidence of Confirmed MI, Stroke, Cardiovascular Death, UA, and TIA Separately
The percentages of subjects with the efficacy endpoints of confirmed MI, stroke, cardiovascular death, UA and TIA are reported separately. \*all other CV death without fatal MI and fatal stroke
Time frame: Until follow-up (approximately 6 years)
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Tucson, Arizona, United States
Unnamed facility
Hot Springs, Arkansas, United States
Unnamed facility
Fremont, California, United States
Unnamed facility
Huntington Park, California, United States
Unnamed facility
Los Angeles, California, United States
...and 456 more locations