A Study to Assess the Efficacy and Safety of Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease "ARRIVE"

Completed

Phase 3 Results

Trial Description

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.

Detailed Description

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

Conditions

Interventions

  • Aspirin (stroke prevention) Drug
    Intervention Desc: Antiplatelet agent; inhibits thromboxane A2
  • Placebo Biological
    Intervention Desc: Placebo, taken daily
    ARM 1: Kind: Experimental
    Label: Arm 2
    ARM 2: Kind: Experimental
    Label: Placebo
    Description: Participants received 1 tablets of matching placebo orally once daily.
  • Aspirin (Acetylsalicylic acid, BAYE4465) Drug
    Intervention Desc: 100mg enteric coated Aspirin, taken daily
    ARM 1: Kind: Experimental
    Label: Arm 1
    ARM 2: Kind: Experimental
    Label: Acetylsalicylic acid (Aspirin, BAYE4465)
    Description: Participants received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients will be randomized to take aspirin or placebo; follow-up for approximately 5 years after being enrolled in trial.

Outcomes

Type Measure Time Frame Safety Issue
Primary Time to first occurrence of the composite outcome of MI, stroke or cardiovascular death.
Secondary Time to first occurrence of the composite outcome of cardiovascular death, ACS (Acute Coronary Syndrome), or stroke; time to first occurrence of the individual components of the primary: MI, stroke or cardiovascular death; time to occurrence/ incidence of all cause mortality; time to first occurrence/ incidence of all cancers, excluding non melanoma skin cancer;time to first occurrence/ incidence of colon cancer; incidence of MI, stroke and CV death.
Primary Time to first occurrence of the composite outcome of MI, stroke or cardiovascular death Approximately 5 years of follow-up (duration of planned treatment phase) No
Secondary Time to first occurrence of the composite outcome of cardiovascular death, ACS (Acute Coronary Syndrome), or stroke Approximately 5 years of follow-up (duration of planned treatment phase) No
Secondary Time to first occurrence of the individual components of the primary: non-fatal MI, total MI, non-fatal stroke, total stroke or cardiovascular death Approximately 5 years of follow-up (duration of planned treatment phase) No
Secondary Time to incidence of all cause mortality Approximately 5 years of follow-up (duration of planned treatment phase) No
Secondary Time to first occurrence of/ incidence of all cancers, excluding non melanoma skin cancer Approximately 5 years of follow-up (duration of planned treatment phase) No
Secondary Time to first occurrence of/ incidence of colon cancer Approximately 5 years of follow-up (duration of planned treatment phase) No
Secondary Incidence of MI, stroke and CV death separately Approximately 5 years of follow-up (duration of planned treatment phase) No
Secondary Incidence of treatment-emergent adverse events (observed and reported), and changes in the physical examination findings, weight, and vital signs Approximately 5 years of follow-up (duration of planned treatment phase) Yes
Primary Time to first occurrence of the composite outcome of MI, stroke, cardiovascular death, UA (unstable angina) or TIA (transient ischemic attack) Approximately 6 years of follow-up (duration of planned treatment phase) No
Secondary Time to first occurrence of the individual components of the primary: non-fatal MI, total MI, non-fatal stroke, total stroke, cardiovascular death, UA or TIA Approximately 6 years of follow-up (duration of planned treatment phase) No
Secondary Incidence of MI, stroke, UA, TIA and CV death separately Approximately 6 years of follow-up (duration of planned treatment phase) No
Primary Time to the First Occurrence of the Composite Outcome of MI (Myocardial Infarction), Stroke, Cardiovascular Death, UA (Unstable Angina) or TIA (Transient Ischemic Attack) Until follow-up (approximate 6 years)
Secondary Time to the First Occurrence of the Composite Outcome of Cardiovascular Death, MI, or Stroke (Ischemic, Hemorrhagic, or Unknown) Until follow-up (approximate 6 years)
Secondary 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 Until follow-up (approximately 6 years)
Secondary Time to All-cause Mortality, the First Occurrence of All Cancers Excluding Non-melanoma Skin Cancer (NMSC) and the First Occurrence of Colon Cancer Until follow-up (approximately 6 years)
Secondary Incidence of All-cause Mortality, All Cancers Excluding Non-melanoma Skin Cancer and Colon Cancer Until follow-up (approximately 6 years)
Secondary Incidence of Confirmed MI, Stroke, Cardiovascular Death, UA, and TIA Separately Until follow-up (approximately 6 years)

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