We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00501059
Recruitment Status : Completed
First Posted : July 13, 2007
Results First Posted : January 8, 2018
Last Update Posted : January 8, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

July 12, 2007
July 13, 2007
November 15, 2017
January 8, 2018
January 8, 2018
July 5, 2007
November 15, 2016   (Final data collection date for primary outcome measure)
Time to the First Occurrence of the Composite Outcome of MI (Myocardial Infarction), Stroke, Cardiovascular Death, UA (Unstable Angina) or TIA (Transient Ischemic Attack) [ Time Frame: Until follow-up (approximate 6 years) ]
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 to first occurrence of the composite outcome of MI, stroke or cardiovascular death [ Time Frame: Approximately 5 years (duration of planned treatment phase) ]
Complete list of historical versions of study NCT00501059 on ClinicalTrials.gov Archive Site
  • Time to the First Occurrence of the Composite Outcome of Cardiovascular Death, MI, or Stroke (Ischemic, Hemorrhagic, or Unknown) [ Time Frame: Until follow-up (approximate 6 years) ]
    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 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 [ Time Frame: Until follow-up (approximately 6 years) ]
    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 to All-cause Mortality, the First Occurrence of All Cancers Excluding Non-melanoma Skin Cancer (NMSC) and the First Occurrence of Colon Cancer [ Time Frame: Until follow-up (approximately 6 years) ]
    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.
  • 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 [ Time Frame: Until follow-up (approximately 6 years) ]
    The percentages of subjects with the efficacy endpoints of confirmed MI, stroke, cardiovascular death, UA and TIA are reported separately.
  • 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
  • TIME FRAME for all secondary outcomes: approximately 5 years (duration of planned treatment phase)
Number of Subjects With Adjudicated GI Bleeding by Severity [ Time Frame: Until follow-up (approximate 6 years) ]
Not Provided
 
A Study to Assess the Efficacy and Safety of Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel Group Study to Assess the Efficacy (Reduction of Cardiovascular Disease Events) and Safety of 100 mg Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease
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
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Moderate Risk of CVD
  • Drug: Aspirin (Acetylsalicylic acid, BAYE4465)
    100mg enteric coated Aspirin, taken daily
  • Drug: Placebo
    Placebo, taken daily
  • Experimental: Acetylsalicylic acid (Aspirin, BAYE4465)
    Participants received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily.
    Intervention: Drug: Aspirin (Acetylsalicylic acid, BAYE4465)
  • Placebo Comparator: Placebo
    Participants received 1 tablets of matching placebo orally once daily.
    Intervention: Drug: Placebo
Chan AT, Cook NR. Are we ready to recommend aspirin for cancer prevention? Lancet. 2012 Apr 28;379(9826):1569-71. doi: 10.1016/S0140-6736(11)61654-1. Epub 2012 Mar 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12546
November 15, 2016
November 15, 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males aged 55 years and above with 2 to 4 risk factors. Male Risk Factors:

    • Elevated cholesterol (Tchol>200 mg/dL or LDL>130 mg/dL; as measured at screening) irrespective of current treatment
    • Current smoking: defined as any cigarette smoking in the past 12 months
    • Low HDL cholesterol (HDL<40 mg/dL; as measured at screening)
    • Elevated blood pressure (SBP>140 mmHg; as measured at screening)
    • Currently on any medication to treat high blood pressure
    • Positive family history of early CHD (a first-degree relative [father, mother, brother, sister, son, daughter] suffered a heart attack [myocardial infarction] before the age of 60 years)
  • Females aged 60 and above with 3 or more risk factors. Female Risk Factors:

    • Elevated cholesterol (Tchol>240 mg/dL or LDL>160 mg/dL; as measured at screening) irrespective of current treatment
    • Current smoking: defined as any cigarette smoking in the past 12 months
    • Low HDL cholesterol (HDL<40 mg/dL; as measured at screening)
    • Elevated blood pressure (SBP>140 mmHg; as measured at screening)
    • Currently on any medication to treat high blood pressure
    • Positive family history of early CHD (a first-degree relative [father, mother, brother, sister, son, daughter] suffered a heart attack [myocardial infarction] before the age of 60 years)
  • An understanding and willingness to comply with trial procedures and has given written informed consent to participate in the trial

Exclusion Criteria:

  • History of a documented vascular event, such as MI, stroke, coronary artery angioplasty or stenting, coronary artery bypass graft, relevant arrhythmias, or congestive heart failure or vascular intervention
  • Patients who are at higher than moderate risk on the basis of their diabetes status, other factors known to the investigator, or the currently used national risk score
  • Known contraindications to the study drug, e.g. hypersensitivity to acetylsalicylic acid
  • Recent (in the past year) history of gastrointestinal or genitourinary bleeding or other bleeding disorders
  • Active diagnosed and documented reflux esophagitis
  • Patients presenting with any medical condition, or psychiatric or substance abuse disorder, that, in the opinion of the investigator, is likely to affect the patient's ability to complete the study or precludes the patient's participation in the study
  • Lactating women or women of childbearing potential
  • Severe liver disease or damage based on the clinical judgment of the investigator
  • Severe renal disease or damage based on the clinical judgement of the investigator
  • A definite indication for acetylsalicylic acid therapy, other antiplatelet drug, or anticoagulant in the opinion of the physician
  • A history of asthma induced by administration of salicylates or substances with a similar action, notably NSAIDS
  • Chronic, frequent (> 5 days/month) use of NSAIDs (including aspirin, or aspirin containing products), COX-2 inhibitors or metamizole
  • Current participation in any other trials involving investigational products within 30 days prior to the Screening Visit
  • Current use of an anticoagulant medication
  • Sitting systolic blood pressure greater than 170 mmHg
Sexes Eligible for Study: All
55 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Ireland,   Italy,   Poland,   Puerto Rico,   Spain,   United Kingdom,   United States
 
 
NCT00501059
12198
2006-003622-29 ( EudraCT Number )
Yes
Not Provided
Not Provided
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP