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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00501059
Other study ID # 12198
Secondary ID 2006-003622-29
Status Completed
Phase Phase 3
First received
Last updated
Start date July 5, 2007
Est. completion date November 15, 2016

Study information

Verified date September 2018
Source Bayer
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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


Recruitment information / eligibility

Status Completed
Enrollment 12546
Est. completion date November 15, 2016
Est. primary completion date November 15, 2016
Accepts healthy volunteers No
Gender All
Age group 55 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Aspirin (Acetylsalicylic acid, BAYE4465)
100mg enteric coated Aspirin, taken daily
Placebo
Placebo, taken daily

Locations

Country Name City State
United States Medical Research Trust Boynton Beach Florida
United States Medical Research Centers of South Florida, Inc. Hollywood Florida
United States Office of Dr.Larry Levinson, DO Hollywood Florida
United States PharmaTrials, Inc. Perth Amboy New Jersey
United States Tallahassee Memorial Family Quincy Florida
United States Merit Medical Group, Inc. Richlands Virginia
United States Helping Hands Clinical Trials Santa Ana California

Sponsors (1)

Lead Sponsor Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Germany,  Ireland,  Italy,  Poland,  Puerto Rico,  Spain,  United Kingdom, 

References & Publications (1)

Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, Howard G, Pearson TA, Rothwell PM, Ruilope LM, Tendera M, Tognoni G; ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate ris — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Number of Subjects With Adjudicated GI Bleeding by Severity Until follow-up (approximate 6 years)
Other Incidence of Composite Outcomes and Non-fatal MI Until follow-up (approximate 6 years)
Other Incidence of Composite Outcomes and Individual Outcomes in Per-protocol Population *all other CV death without fatal MI and fatal stroke. Until follow-up (approximate 6 years)
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) 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. 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) 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. 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 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. 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 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. 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 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 Until follow-up (approximately 6 years)