ASPirin in Reducing Events in the Elderly

ISRCTN	ISRCTN83772183
DOI	https://doi.org/10.1186/ISRCTN83772183
ClinicalTrials.gov number	NCT01038583

Submission date: 03/05/2005
Registration date: 14/07/2005
Last edited: 18/03/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Study website

Contact information

Prof John McNeil
Scientific

Department of Epidemiology and Preventive Medicine
Monash University
Alfred Hospital
Commercial Rd
Melbourne
3004
Australia

Phone	+61 (0)3 9903 0555
Email	john.mcneil@monash.edu

Study information

Study design	Randomized controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	GP practice
Study type	Prevention
Scientific title	ASPirin in Reducing Events in the Elderly: a randomised controlled trial
Study acronym	ASPREE
Study hypothesis	Added 13/01/2017: Null hypothesis as of 2010: Daily 100 mg enteric-coated aspirin will have no benefit over placebo in prolonging life, or life free of dementia or life free of significant physical disability in healthy participants aged 70 years and over. Hypothesis amended as of 14/03/2008: Null hypothesis: Low-dose aspirin does not prolong life free of mental or physical disability in those aged 70 years and over who has not manifested cardiovascular disease or dementia. Provided at time of registration: Null hypothesis: Low-dose aspirin has no overall benefit in those aged 70 years and over who do not have manifest cardiovascular disease or dementia.
Ethics approval(s)	1. The Royal Australasian College of General Practitioners Ethics Committee, approved 2002, ref: NREEC 02/22b 2. Monash University Human Research Ethics Committee, approved 2006, ref: 2006/745MC 3. The Tasmanian Human Research Ethics Committee, approved 2006, ref: H0008933 4. The Goulburn Valley Health Ethics & Research Committee, Shepparton, approved 2007, ref: GVH-21/07 5. The ACT Health Human Research Ethics Committee, Canberra, approved 2007, ref: 11/07.997 6. The University of Adelaide Human Research Ethics Committee, approved 2011, ref: H-250-2011 7. Numerous IRBs in the USA
Condition	Mental and physical disability in the elderly
Intervention	Acetylsalicylic acid 100 mg: enteric coated unscored white tablet Placebo of acetylsalicylic acid: enteric coated unscored white tablet with identical appearance
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Acetylsalicylic acid
Primary outcome measure	Amended 02/03/2009: 1. Death from any cause 2. Incident dementia, defined according to the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV) criteria 3. Persistent physical disability, defined as the onset of a lot of difficulty to inability to perform any one of 6 Katz Activities of Daily Living Updated as of 14/03/2008: 1. Death from any cause 2. Death from incident dementia, defined according to the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV) criteria 3. Death from persistent physical disability, defined as progression by at least 2 intervals on a 5-point scale of any one of the 6 Katz Activities of Daily Living Provided at time of registration: 1. Coronary artery disease death 2. Cardiac failure death (with coronary cause), and other coronary death 3. Cardiac failure death - due to heart failure (prior grade III-IV dyspnea New York Heart Association [NYHA]), with any defined non-coronary cause 4. Other vascular death 5. Non-coronary cardiac death 6. Cerebrovascular disease death 7. Non-fatal cardiovascular events 8. Non-fatal cerebrovascular events
Secondary outcome measures	Added 13/01/2017: Secondary outcome measures since 2009: 1. All-cause mortality 2. 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 3. Fatal and non-fatal cancer, excluding non-melanoma skin cancer 4. Dementia (added in 2013) 5. Mild cognitive impairment 6. Physical disability 7. Depression 8. Major hemorrhagic events Secondary outcome measures updated as of 14/03/2008: 1. All-cause mortality 2. Fatal and non-fatal cardiovascular events including: 2.1. Coronary heart disease death 2.3. Non-fatal myocardial infarction 2.3. Fatal and non-fatal stroke 2.4. Hospitalisation for heart failure 3. Fatal and non-fatal cancer, excluding non-melanomatous skin cancer 4. Dementia 5. Cognitive decline 6. Physical disability 7. Major haemorrhagic events Secondary outcome measures provided at time of registration: 1. All-cause dementia Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria 2. Cognitive decline - defined as 2 point decline on 3MSE supplemented by a Color Trail test 3. Clinically significant bleeding including gastrointestinal hemorrhages or hemorrhages at other sites that required transfusion, hospitalization and or surgery Current tertiary outcome measures as of 29/08/2018: 1. Cognitive function 2. Physical performance 3. Quality of life 4. Haemoglobin levels 5. Hospitalisations - total and for reasons other than endpoints 6. Urinary albumin:creatinine ratio Original tertiary outcome measures: 1. Haemorrhagic stroke 2. Transient ischaemic attack 3. Hospitalisation for unstable angina 4. Total mortality 5. Cognitive decline 6. Depression score 7. Quality of life 8. Disability 9. A fall in haemoglobin 10. Fatal and non-fatal cancer 11. Total hospitalisations 12. Hospitalisation for reasons other than primary endpoints 13. Institutionalisation 14. Cost-effectiveness of aspirin 15. Public health outcomes 16. Development of a multivariate model which predicts in different age strata (70-79 and 80+ years) the likelihood of death, dementia, disability, and self-assessed quality of life 17. Risk-benefit trade-off associated with the use of aspirin in different categories
Overall study start date	01/03/2003
Overall study end date	31/12/2017

Eligibility

Participant type(s)	Healthy volunteer
Age group	Senior
Lower age limit	65 Years
Sex	Both
Target number of participants	19,000
Total final enrolment	19114
Participant inclusion criteria	Current inclusion criteria as of 13/01/2017: 1. African American and Hispanic men and women 65 years of age and over (in the USA), all other men and women 70 years of age and over 2. Willing and able to provide informed consent, and willing to accept the study requirements Previous inclusion criteria: All subjects will be aged 70 years or more and capable of attending their usual family physician's clinic and providing informed consent
Participant exclusion criteria	Current exclusion criteria as of 13/01/2017: 1. A history of a diagnosed cardiovascular event defined as MI, congestive heart failure, angina pectoris (± nitrate use), 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 2. A clinical diagnosis of atrial fibrillation 3. A serious intercurrent illness likely to cause death within the next 5 years, such as terminal cancer or obstructive airways disease 4. A current or recurrent condition with a high risk of major bleeding, e.g. cerebral aneurysm or cerebral AV malformation, any bleeding diathesis, gastrointestinal malignancy, recent peptic ulcer, liver disease, esophageal varicosities, uremia, aortic aneurysm or any other condition known to be associated with a high risk of serious bleeding 5. Anemia, i.e. hemoglobin level below the normal value for the gender of the participant (males: <12 g/dL, females: <11 g/dL) (Note: Hemoglobin levels within the normal range in a participant taking therapy for anemia will not be an exclusion criterion). 6. Absolute contraindication or allergy to aspirin 7. Current participation in a clinical trial 8. Current continuous use of aspirin for secondary prevention 9. Current continuous use of other anti-platelet drug or anticoagulant 10. A systolic blood pressure ≥180 mmHg and / or a diastolic blood pressure ≥105 mmHg 11. A history of dementia or a Modified Mini-Mental State Examination (3MS) score  77 as measured at Visit 1: Lifestyle Profile and Screening 12. Severe difficulty or an inability to perform any one of the 6 Katz ADLs, as determined at Visit 1: Lifestyle Profile and Screening 13. Pill-taking compliance below 80% during the placebo run-in phase. Previous exclusion criteria: 1. A history of cardiovascular morbidity defined as myocardial infarction, stroke, peripheral vascular disease, angina, transient ischaemic attack, greater than 50% carotid stenosis or previous carotid endarterectomy or stenting, coronary artery angioplasty or stenting, or coronary artery bypass grafting 2. A serious intercurrent illness likely to cause death within the next 5 years 3. A current or recurrent condition with a high risk of major bleeding e.g. cerebral aneurysm or cerebral arteriovenous (AV) malformation, any bleeding diathesis, gastrointestinal malignancy, peptic ulcer, liver disease, uraemia, aortic aneurysm or any other condition known to be associated with a high risk of serious bleeding 4. Absolute contraindication or allergy to aspirin 5. Current participation in a clinical trial 6. Current continuous use of aspirin or other anti-platelet drug or anticoagulant 7. A history of diabetes or dementia 8. In addition those who lie outside of tolerance levels of 8-104% during placebo run-in phase will not be randomised The following criteria were added as of 14/03/2008: 9. An inability to perform independently one of the 6 Katz Activities of Daily Living (walking, bathing, dressing, transferring from chair or bed, toileting, eating) 10. Pill taking compliance below 80% on tablet count during a placebo run-in phase The following criterion was amended to the below text as of 20/02/2009: 7. A history of dementia
Recruitment start date	31/03/2010
Recruitment end date	31/12/2014

Locations

Countries of recruitment

Australia
United States of America

Study participating centres

Monash University

Melbourne
3004
Australia

Berman Center for Clinical Outcomes Research

Minneapolis Medical Research Foundation
Hennepin County Medical Center
Minneapolis
-
United States of America

Sponsor information

Monash University (Australia)
University/education

Research and Graduate Programs Office
Faculty of Medicine, Nursing and Health Sciences
PO Box 64
Victoria
3800
Australia

Phone	+61 (0)3 9905 1206
Email	robyn.woods@med.monash.edu.au
Website	http://www.monash.edu.au/
"ROR"	https://ror.org/02bfwt286

Funders

Funder type

Research council

National Health and Medical Research Council (ref: 334047)
Government organisation / National government

Alternative name(s): NHMRC
Location: Australia

National Institute on Aging
Government organisation / National government

Alternative name(s): U.S. National Institute on Aging, The National Institute on Aging, NIH NATIONAL INSTITUTE ON AGING, NIA
Location: United States of America

National Cancer Institute
Government organisation / National government

Alternative name(s): Instituto Nacional del Cáncer, National Cancer Institute at the National Institutes of Health, Instituto Nacional del Cáncer de los Institutos Nacionales de la Salud, NCI
Location: United States of America

Monash University
Government organisation / Universities (academic only)

Alternative name(s): Monash Uni | Melbourne, Monash Uni, University of Monash, Universitas Monash, MU
Location: Australia

Victorian Cancer Agency
Government organisation / Local government

Alternative name(s): Victorian Cancer Agency, Department of Health and Human Services, VCA
Location: Australia

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other publications	rationale	01/07/2003		Yes	No
Other publications	design	01/11/2013		Yes	No
Other publications	rationale for ASPREE-D substudy	01/10/2016		Yes	No
Other publications	baseline characteristics	12/10/2017		Yes	No
Other publications	rationale for SNORE-ASA sub-study	01/01/2018		Yes	No
Statistical Analysis Plan	statistical analysis plan	01/04/2018		No	No
Other publications	development of a standardized definition for clinically significant bleeding	22/05/2018	03/07/2019	Yes	No
Results article	results	18/10/2018	03/07/2019	Yes	No
Results article	results	18/10/2018	03/07/2019	Yes	No
Results article	results	18/10/2018	03/07/2019	Yes	No
Results article	results	09/12/2019	10/12/2019	Yes	No
Results article	results	01/05/2019	01/04/2020	Yes	No
Results article	results	27/12/2019	02/04/2020	Yes	No
Results article	results	01/09/2020	04/08/2020	Yes	No
Results article	results	01/12/2020	03/11/2020	Yes	No
Results article		01/08/2020	26/05/2021	Yes	No
Results article		01/01/2021	29/06/2021	Yes	No
Results article		01/06/2021	29/06/2021	Yes	No
Results article		06/07/2021	29/06/2021	Yes	No
Results article		01/03/2021	30/07/2021	Yes	No
Results article		01/10/2020	01/09/2021	Yes	No
Results article		26/02/2020	26/11/2021	Yes	No
Results article		30/01/2023	31/01/2023	Yes	No
Other publications	Secondary analysis	03/07/2023	27/07/2023	Yes	No
Other publications	Secondary analysis	21/11/2023	27/11/2023	Yes	No
Other publications	Associations between low sex steroid concentrations and incidence of knee and hip replacement for osteoarthritis in community-dwelling older women	14/12/2024	19/12/2024	Yes	No
Other publications	Frailty incidence by diabetes treatment regimens	17/03/2025	18/03/2025	Yes	No

Editorial Notes

18/03/2025: Publication reference added.
19/12/2024: Publication reference added.
27/11/2023: Publication reference added.
27/07/2023: Publication reference added.
31/01/2023: Publication reference added.
26/11/2021: Publication reference added.
01/09/2021: Publication reference added.
30/07/2021: Publication reference added.
29/06/2021: Publication references added.
26/05/2021: Publication reference added.
03/11/2020: Publication reference added.
04/08/2020: Publication reference added.
02/04/2020: Publication reference added.
01/04/2020: Publication reference added.
10/12/2019: Publication reference added.
03/07/2019: Publication references and enrolment added.
27/02/2019: Publication reference added.
31/08/2018: The following changes have been made:
1. The overall trial end date has been changed from 31/12/2015 to 31/12/2017.
2. The recruitment start date has been changed from 01/03/2003 to 31/03/2010.
3. The recruitment end date has been changed from 31/12/2015 to 31/12/2014.
29/08/2018: The tertiary outcome measures (listed in the secondary outcome measures field) have been changed.
28/08/2018: Associate Professor Robyn Woods of Monash University, Executive Director and Chief Investigator of ASPREE, has confirmed that the ISRCTN record for ASPREE will not be further updated by the investigators. Please check ClinicalTrials.gov for the most up-to-date version (https://clinicaltrials.gov/ct2/show/NCT01038583 ).
23/08/2018: The following changes have been made:
1. The National Heart Foundation has been removed as a funder. It was not involved in funding the main ASPREE study, only a pilot trial.
2. Publication references added.
22/08/2018: Bayer AG (Australia) was removed as a funder. Bayer provided the study drug, but did not fund the trial. The National Institute on Aging, the National Cancer Institute, Monash University and the Victorian Cancer Agency have been added as funders.
20/07/2018: Publication reference added.
13/01/2017: USA was added to the countries of recruitment.
20/02/2009: The target number of participants was changed from 18,000 to 19,000.
14/03/2008: The following changes were made to the trial record:
1. The overall trial end date was changed from 30/06/2005 to 31/12/2015.
2. The target number of participants was changed from 20,500 to 18,000.