Aspirin in Reducing Events in the Elderly

Study Overview
=================
Brief Summary
-----------------
ASPREE-XT is a post-treatment, longitudinal observational follow-up study of ASPREE participants [ASPREE Investigator Group, 2013; www.aspree.org; McNeil et al 2017]. Although the ASPREE trial medication was ceased, the study activity was not stopped and ASPREE participants are continuing with scheduled visits and phone calls. An observational follow-up phase (ASPREE-XT), began in January, 2018. This will enable the monitoring of possible delayed effects of aspirin treatment, primarily on cancer incidence, metastases and mortality. In addition to monitoring the incidence of malignancy within the ASPREE cohort, the opportunity will be taken to observe any other residual effects of aspirin on the endpoints being monitored in the cohort. Continuity of contact with study participants is the key to retention of the cohort for any ongoing or future studies.

Detailed Description
-----------------
ASPREE BACKGROUND: ASPREE (ASPirin in Reducing Events in the Elderly) is a joint US/Australian research project aiming to determine whether low-dose aspirin increases healthy life-span, defined as survival free of dementia and disability. ASPREE began in 2010 and completed recruitment in 2014. It is a randomized, double-blind, placebo-controlled, primary prevention trial of daily 100 mg of aspirin in a population of healthy older people in the United States (US) and Australia with a period of treatment averaging 4.5 years. ASPREE's primary outcome is length of survival free of dementia and disability and has secondary outcomes encompassing the major health issues related to aging. The trial involving 19,114 persons aged 70 and above (65 years and above for US minorities) is distinctive for its large size, methodological rigor and high participant retention rate in both countries. ASPREE UNIQUE ASPECTS: It is the first large scale trial to incorporate dementia-free and disability-free survival as a primary outcome. This is now recognized as an appropriate goal of treatment in a primary prevention population of this age group. Within a clinical trial context disability-free survival incorporates an estimate of the overall benefits and risks of aspirin in a single outcome measure. It is one of the first primary prevention trials of aspirin to include cancer incidence, metastases or mortality as a pre-specified endpoint. Recent meta-analyses [Rothwell et al 2010, 2011, 2012] suggests that aspirin has a significant chemopreventive effect becoming evident after a period of 4+ years of aspirin treatment, but questions remain about the magnitude of benefit, and whether it applies to treatment of all cancers and to older people. It will provide information about the impact of aspirin on a range of other conditions (e.g, dementia, CVD, stroke, depression, bleeding) where aspirin has been claimed to have benefit (or risks). The intervention phase of the trial ended in June 2017 after the NIA determined that it was highly unlikely that aspirin would show a benefit on the overall primary outcome within the planned 5-year time frame. The study is now entering a data cleaning and analysis phase and it is anticipated that the primary results were published in September 2018.

Official Title
-----------------
Aspirin in Reducing Events in the Elderly

Conditions
-----------------
Functional Disability, Dementia, Heart Disease, Stroke, Cancer, Bleeding, Depression

Intervention / Treatment
-----------------
* Drug: 100 mg enteric-coated aspirin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women African American and Hispanic persons age 65 or older Any person from another ethnic minority group and Caucasian persons age 70 or older Willing and able to provide informed consent, and willing to accept the study requirements Exclusion Criteria: A history of a diagnosed cardiovascular event A serious intercurrent illness likely to cause death within the next 5 years, such as terminal cancer or obstructive airways disease A current or recurrent condition with a high risk of major bleeding, ex: cerebral aneurysm Anemia Absolute contraindication or allergy to aspirin Current participation in a clinical trial Current continuous use of aspirin or other anti-platelet drug or anticoagulant for secondary prevention. People with previous use of aspirin for primary prevention may enter the trial, provided they agree to cease existing use of aspirin and understand that they may be subsequently randomly allocated to low dose aspirin or placebo. A systolic blood pressure ≥180 mmHg and / or a diastolic blood pressure ≥105 mmHg A history of dementia Severe difficulty or an inability to perform any one of the 6 Katz ADLs Non-compliance to taking pill

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aspirin<br>100 mg enteric-coated aspirin | Drug: 100 mg enteric-coated aspirin<br>* 100 mg enteric-coated aspirin, taken daily<br>|
| Placebo<br>Placebo | Drug: Placebo<br>* 100 mg enteric-coated placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is death from any cause or incident, dementia or persistent physical disability. | Dementia will be diagnosed based on DSM-IV criteria. Significant physical disability will be defined as a confirmed, and persisting for at least 6 months, self-report of 'a lot of difficulty', or 'inability to perform independently' any one of the 6 Katz basic Activities of Daily Living (ADLs).75 | every 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | every 6 months | 
| Fatal and non fatal cardiovascular events including a) coronary heart disease death, b) non-fatal MI, c) fatal and non-fatal stroke and d) any hospitalization for heart failure |  | every 6 months | 
| Fatal and non-fatal cancer, excluding non-melanoma skin cancer |  | every 6 months | 
| Dementia |  | every 6 months | 
| Mild Cognitive Impairment (MCI; assessed using the Modified Mini-Mental State Examination or 3MS 70 and other cognitive function measures - see below) |  | every 6 months | 
| Physical disability |  | every 6 months | 
| Major hemorrhagic events |  | every 6 months | 
| Depression |  | Annually | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aspirin, Prevention, Healthy, Over 70 years old, ASPREE, Aspirin in Reducing Events in the Elderly, Australia, Functional disability, Dementia, Heart Disease/ Stroke, Cancer, Bleeding