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 #10 (25.08.2026)

This brief update aims to keep researchers informed of developments with the ASPREE project. For further information about matters in this newsletter please feel free to contact a study PI.

We are pleased to share that with new funding from the National Cancer Institute in the U.S, ASPREE is beginning its third phase, called ASPREE-LT (Long-Term). This support allows us to continue phone-call/medical record-based follow up of participants, with a particular focus on cancer and healthy ageing. We are grateful for the ongoing support from our participants, funders and collaborators, which will enable ASPREE-LT to drive impactful research for ageing health.

The ASPREE website maintains a publications list which highlights the breadth of research undertaken using ASPREE data. These include:

Cancer incidence and mortality with aspirin in older adults: follow-up of the ASPREE trial
In the ASPREE RCT phase, there was an increase in cancer mortality noted in the aspirin arm. In the post-intervention phase (ASPREE-XT) there was no difference in cancer mortality risk between those originally assigned to aspirin vs placebo. 
Orchard et al, JAMA Oncology. 2026;12(3):285-294    https://doi.org/10.1001/jamaoncol.2025.6196

Frailty trajectories after a cardiovascular event among community-dwelling older people
Incident CVD increases frailty burden in older adults, with older age, living alone and living outside a major city associated with greater frailty burden after a CVD event.
Phyo AZZ et al, Eur J Prevent Cardiol. 2025  https://doi.org/10.1093/eurjpc/zwaf095

Longitudinal changes in heart stress and the risk for cardiovascular disease and mortality in older adults: An observational study
Heart stress based on longitudinal changes in NT-proBNP concentration may improve risk stratification of CVD and mortality in older adults.
Cai A, et al. Ann Intern Med. 2026    https://doi.org/10.7326/ANNALS-26-00245

Distributed on behalf of the ASPREE PIs
Rory Wolfe (rory.wolfe@monash.edu)
Anne Murray (AMurray@bermancenter.org)
Andy Chan (ACHAN@mgh.harvard.edu)
Joanne Ryan (joanne.ryan@monash.edu)

To subscribe to this newsletter please email aspree@monash.edu

View past ASPREE PI Updates