ASPREE: Aspirin in Reducing Events in the Elderly

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Functional Disability Dementia Heart Disease Stroke Cancer Bleeding Depression	Drug: 100 mg enteric-coated aspirin Drug: Placebo

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.

Study Design

Study Type:

Observational

Actual Enrollment :

19114 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Aspirin in Reducing Events in the Elderly

Actual Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Dec 1, 2017

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Aspirin 100 mg enteric-coated aspirin	Drug: 100 mg enteric-coated aspirin 100 mg enteric-coated aspirin, taken daily
Placebo Placebo	Drug: Placebo 100 mg enteric-coated placebo

Arm

Intervention/Treatment

Aspirin

100 mg enteric-coated aspirin

Drug: 100 mg enteric-coated aspirin

100 mg enteric-coated aspirin, taken daily

Placebo

Drug: Placebo

100 mg enteric-coated placebo

Outcome Measures

Primary Outcome Measures

The primary endpoint is death from any cause or incident, dementia or persistent physical disability. [every 6 months]
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

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Palo Alto Medical Foundation Research Institute	Palo Alto	California	United States	94301
3	Howard University	Washington	District of Columbia	United States	20060
4	University of Florida Department of Aging and Geriatrics	Gainesville	Florida	United States	32611
5	Morehouse School of Medicine	Atlanta	Georgia	United States	30310
6	Emory/ Atlanta VAMC	Atlanta	Georgia	United States	30322
7	Georgia Health Sciences University	Augusta	Georgia	United States	30912
8	Rush Alzheimer's Disease Center	Chicago	Illinois	United States	60612
9	University of Iowa	Iowa City	Iowa	United States	52242
10	Kansas University Medical Center	Kansas City	Kansas	United States	66106
11	Pennington Biomedical Research Center	Baton Rouge	Louisiana	United States	70808
12	Mary Bird Perkins Our Lady of the Lake Cancer Center	Baton Rouge	Louisiana	United States	70809
13	LSU Health Sciences- New Orleans	New Orleans	Louisiana	United States	70112
14	Tulane Medical Center	New Orleans	Louisiana	United States	70112
15	LSU Health Sciences- Shreveport	Shreveport	Louisiana	United States	71130
16	University of Michigan	Ann Arbor	Michigan	United States	48109
17	Wayne State University	Detroit	Michigan	United States	48201
18	Henry Ford Health System	Detroit	Michigan	United States	48202
19	Detroit Clinical Research Center	Novi	Michigan	United States	48377
20	HealthPartners Research Institute	Minneapolis	Minnesota	United States	55425
21	Phalen Village Clinic	Saint Paul	Minnesota	United States	55106
22	Central Jersey Medical Center	Elizabeth	New Jersey	United States	07202
23	Winthrop University Hospital	Mineola	New York	United States	11501
24	Wake Forest University Baptist Medical Center	Greensboro	North Carolina	United States	27408
25	The Brody School of Medicine at ECU	Greenville	North Carolina	United States	27834
26	Albert Einstein Medical Center	Philadelphia	Pennsylvania	United States	19141
27	University of Pittsburgh Health Sciences Research Center	Pittsburgh	Pennsylvania	United States	15260
28	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island	United States	02860
29	University of Tennessee Health Science Center	Memphis	Tennessee	United States	38105
30	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390
31	University of TX Medical Branch	Galveston	Texas	United States	77555
32	Regional Academic Health Center	Harlingen	Texas	United States	78550
33	UT Health Science Center at San Antonio	San Antonio	Texas	United States	78229
34	Clinical Trials Unit, The Canberra Hospital	Garran	Australian Capital Territory	Australia	2605
35	Illawarra Health and Medical Research Institute, University of Wollongong	Wollongong	New South Wales	Australia	2522
36	Discipline of General Practice, School of Population Health, University of Adelaide	Adelaide	South Australia	Australia	5005
37	Greater Green Triangle University	Mount Gambier	South Australia	Australia	5290
38	University of Tasmania Rural Clinical School	Burnie	Tasmania	Australia	7320
39	The Menzies Institute for Medical Research, University of Tasmania	Hobart	Tasmania	Australia	7000
40	University of Tasmania Newnham Campus	Launceston	Tasmania	Australia	7250
41	Bendigo Regional Clinical School	Bendigo	Victoria	Australia	3550
42	Geelong Hospital	Geelong	Victoria	Australia	3220
43	Monash Mildura Regional Clinical School	Mildura	Victoria	Australia	3500
44	University of Ballarat	Mount Helen	Victoria	Australia	3350
45	Monash Gippsland Regional Clinical School	Traralgon	Victoria	Australia	3844
46	The South West Alliance of Rural Health (SWARH)	Warrnambool	Victoria	Australia	3280
47	Gateway Community Health	Wodonga	Victoria	Australia	3690

Sponsors and Collaborators

Hennepin Healthcare Research Institute
National Health and Medical Research Council, Australia
Bayer
Monash University
Berman Center for Outcomes and Clinical Research
National Institute on Aging (NIA)
National Cancer Institute (NCI)

Investigators

Principal Investigator: Anne Murray, MD, MSc, Berman Center for Outcomes and Clinical Research
Principal Investigator: John McNeil, MBBS, PHD, Monash University