Recruitment for the ASPREE Clinical Trial
Participants were recruited for the ASPREE Clinical Trial through two methods: general practice-based recruitment and community-based recruitment.
General Practitioner Recruitment
In Australia, recruitment occurred predominantly through general practice with General Practitioners (GPs) registered as ASPREE co-investigators. GPs’ clinical databases were searched by inclusion/exclusion criteria and a mailing list created. After GP review, a final list of potential participants was used to generate invitation letters, sent by ASPREE on behalf of the GP. The letter directed the participant to respond to a toll-free telephone number and, upon calling the number, interested participants were screened and suitable persons invited to Visit 1 (week zero) at the GP’s clinic or a community venue. After an interim GP visit to discuss the study and check suitability (including eligibility pathology), participants returned at week four for Visit 2. Further information about Australian recruitment has been published elsewhere.
In the US, recruitment for the ASPREE Clinical Trial was community-based utilising a range of methods such as clinic-based research centres, mailing lists, media advertisements, pre-existing registries and electronic medical records. Select sites in the US recruited Caucasians with a special focus on enriching the group with minority groups (African Americans, Hispanics, Native Americans and others). African American and Hispanic groups had a lower age criterion due to a higher burden of disease and a survival disadvantage. Minority recruitment was challenging due to a lower number of minorities without previous cardiovascular events, disability or dementia, who were not already taking aspirin, and were not reluctant to cease aspirin if not clinically indicated. In addition, after a U.S. National Institutes of Health (NIH) moratorium on recruiting US Caucasians was enacted in 2011, there was increased hesitancy expressed by minorities regarding why ASPREE was only recruiting minorities. This, at least in part, is why US recruitment numbers were lower compared to Australia.
Inclusion and Exclusion Criteria
- Non-minority men and women 70 years of age and older
- US minority (African American and Hispanic) 65 years of age and older
- Willing and able to provide informed consent
- A history of a diagnosed cardiovascular disease (CVD) event defined as a myocardial infarction (MI), heart failure, angina pectoris, stroke, transient ischemic attack, 50% carotid stenosis or previous carotid endarterectomy or stenting, coronary artery angioplasty or stenting, coronary artery bypass grafting, or abdominal aortic aneurysm
- A clinical diagnosis of atrial fibrillation
- Serious illness likely to cause death within the next five years
- A current or recurrent condition with a high risk of major bleeding
- Anemia (hemoglobin < 12 g/dl males, < 11 g/dl females)
- An absolute contraindication or allergy to aspirin
- Current participation in an ongoing clinical trial
- Current use of aspirin for secondary prevention
- Current continuous use of other antiplatelet drug or anticoagulant
- A systolic blood pressure ≥ 180 mm Hg and/or a diastolic blood pressure ≥ 105 mm Hg
- A history of dementia or a Modified Mini-Mental State Examination (3MS) score ≤77;
- Severe difficulty or an inability to perform any one of the six modified Katz Activities of Daily Living (ADL);
- Pill-taking compliance ≤80% during a four week placebo run-in phase
People with current use of aspirin for reasons other than secondary prevention entered the trial after agreeing to discontinue aspirin. Chronic use of non-steroidal anti-inflammatory drugs was not an exclusion criterion. During a four-week run-in phase, participants took placebo for compliance checking. Participants were initially instructed to take their study drug half an hour prior to any morning medication to minimise drug interactions. This instruction was subsequently rescinded.
Randomisation and Intervention
Participants were randomised remotely via AWARD-Data (module of the AWARD system utilised for collecting data from participants) according to a computer-generated randomisation schedule, in a ratio of 1:1 to active or placebo therapy. Randomisation was stratified by general practice in Australia, by regional site in the US and by age in both countries (65–69 years, 70–79 years, 80 years+). Randomisation was blocked within strata and utilised variable sized blocks of two, four or six.
Participants in the study were allocated to one of two treatments: 100 mg enteric-coated unscored white tablet [Bayer Pharma AG (Germany)] or enteric-coated unscored white placebo tablet with identical appearance.
The ASPREE Clinical Trial concluded in June 2017. Study medication administration was ceased immediately and medication bottles were retrieved from all participants, by mail or at in-person visits, to enable confirmation pill counting.