FOR RESEARCHERS

ASPREE Clinical Trial Protocol

Objectives and measures of the ASPREE clinical trial

• The primary objective was to determine whether low-dose aspirin prolonged life free of dementia or persistent physical disability in the healthy elderly.
• Secondary objectives related to the effects of low-dose aspirin on the key outcome areas of death, CVD, dementia and cognitive decline, depression cancer, physical disability and major bleeding episodes.

Protocol summary

• ASPREE was a double-blind, randomised, placebo-controlled primary prevention trial to determine whether daily active treatment of 100 mg enteric-coated aspirin extended the duration of disability-free life in healthy participants aged 70 years and above.
• The study examined whether the potential benefits of low-dose aspirin (particularly the prevention of heart disease, stroke, certain cancers and dementia) outweighed the risks (particularly from GI bleeding and haemorrhagic stroke) in this age group.
• Participants were eligible for the trial if they did not have a current clinical indication for aspirin (i.e. overt cardiovascular disease) or contraindication (i.e. allergy or increased risk of bleeding)  and did not have dementia, significant physical disability, low haemoglobin levels, or a condition that was likely to be fatal during the 5 years of the trial.  All were capable of attending their usual General Practitioner’s (GP’s) clinic and providing informed consent.
• Sample size estimate required 19,000 participants to provide 90% power of a true relative risk benefit of 0.90 for the primary endpoint (a composite of all-cause mortality, incident dementia and persistent physical disability) in an intention-to-treat analysis with an average follow-up of 5 years.
• The trial received financial support from the National Institute on Aging and the National Cancer Institute (NIA and NCI; part of the National Institutes of Health in the USA), the National Health and Medical Research Council of Australia, Monash University and the Victorian Cancer Agency.
• Bayer Pharma (Germany) provided in-kind support through the provision of low-dose aspirin and matching placebo and had no other involvement in the trial.
• The trial was conducted in community settings.

Download the ASPREE Clinical Trial Protocol

ASPREE-XT Study Protocol

Objectives and measures of the ASPREE follow up study, ASPREE-XT

• The primary objective of ASPREE-XT is to determine whether there are delayed effects after a median 4.7 years of treatment with daily low-dose aspirin.  Suggestive evidence of such a ‘legacy’ effect has been identified with cancer and ASPREE-XT will provide an opportunity to confirm or refute this observation in a post clinical trial setting.
• Similar observations will be made on other outcomes including all-cause mortality, physical disability, cancer, dementia and cognitive impairment, depression and frailty and the incidence of cardiovascular disease.
• An additional objective is to study the impact of genomic, lifestyle and environmental factors on the maintenance of good physical and cognitive health amongst older adults.

Protocol summary

• ASPREE-XT is a longitudinal, observational follow-up study of ASPREE participants.
• The study will determine whether legacy effects of aspirin develop following an earlier period of treatment with low-dose aspirin.
• An additional objective is to identify genomic, lifestyle and environmental factors that may contribute to the maintenance of good health in older adults.
• Study methodology and measures are similar to that of the ASPREE clinical trial.
• ASPREE-XT is funded by the National Institute on Aging  and the National Cancer Institute (NIA and NCI; part of the National Institutes of Health in the USA) and the National Health and Medical Research Council of Australia.
• The study is conducted in community settings.

Download the ASPREE-XT Study Protocol

Data Access and Collaboration

ASPREE clinical trial data is managed through a partnership of USA and Australian study collaborators. Data is available to partnering and external researchers for projects of appropriate scientific merit. Expressions of interest to analyse data from the ASPREE clinical trial and/or sub-studies including biospecimens, are co-ordinated through the ASPREE Access Management Site (AMS).

View a list of approved projects in the AMS here.

PI updates for researchers

ASPREE Update #9 (01.03.2022)

This brief update aims to keep researchers informed of developments with the ASPREE project. It is being sent to key ASPREE committee members, collaborators and end-point adjudicators. For further information about matters in this newsletter please feel free to contact a study PI.

Dear Colleagues,

ASPREE participants with moderate alcohol intake had a reduced risk of CVD events and death
Compatible with similar evidence of benefit from alcohol seen in studies of younger people
Confounding by association of alcohol use with socio-economic status and lifestyle factors cannot be excluded.
Neumann J et al. Eur J Preventive Cardiol 2021 DOI: 10.1093/eurjpc/zwab177

Low-dose aspirin (LDA) does not slow onset of frailty in older adults
Previously noted association of frailty with low-grade inflammation raised possibility that LDA might be beneficial
There remains no proven intervention effective in delaying frailty.
Espinoza SE et al. J Gerontol A Biol Sci Med Sci. 2021 Nov 10:glab340. doi: 10.1093/gerona/glab340

The draft US Preventive Services Task Force Statement recommends against the initiation of low-dose aspirin for primary prevention of CVD in adults ≥ 60 years
This new recommendation was significantly influenced by the results of the ASPREE RCT
The Task Force noted the role of aspirin in primary prevention would evolve ‘in the context of declining smoking rates, increasing statin use and more aggressive hypertension management’.
USPSTF. Aspirin use to prevent cardiovascular disease: preventive medication. Oct 12, 2021

Distributed on behalf of the ASPREE PIs
John McNeil (john.mcneil@monash.edu)
Anne Murray (AMurray@bermancenter.org)
Andy Chan (ACHAN@mgh.harvard.edu)
Danny Liew (danny.liew@monash.edu)

To subscribe to this newsletter please email john.mcneil@monash.edu.

View past ASPREE PI Updates