Condition category
Circulatory System
Date applied
31/01/2002
Date assigned
31/01/2002
Last edited
26/11/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof FGR Fowkes

ORCID ID

Contact details

Wolfson Unit for Prevention of Peripheral Vascular Diseases
University of Edinburgh
Teviot Place
Edinburgh
EH8 9AG
United Kingdom
+44 (0)131 650 3219
Gerry.Fowkes@ed.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RG/97006; 057762

Study information

Scientific title

Randomised controlled trial of low dose Aspirin in the prevention of cardiovascular events and death in subjects with Asymptomatic Atherosclerosis

Acronym

AAA Trial

Study hypothesis

Primary prevention strategies aimed at modifying cardiovascular risk factors in otherwise healthy individuals have proved of only limited benefit in the primary prevention of cardiovascular disease. It is possible to identify in the general population large numbers of subjects with asymptomatic preclinical atherosclerosis who are at high risk of subsequent cardiovascular events using a simple blood pressure measurement - the Ankle Brachial Pressure Index (ABPI). We are currently conducting the first prevention trial on such high-risk subjects to determine whether low dose aspirin can reduce the incidence of cardiovascular events and death. 3,350 subjects aged over 50 years with an ABPI of at least 0.95 but no history of cardiovascular disease have been randomised into this double-blind placebo-controlled trial.

The principal hypothesis is that treatment of subjects with asymptomatic atherosclerosis, using low-dose aspirin, prevents subsequent cardiovascular disease indicated by incidence of major cardiovascular and cerebrovascular events.

An additional endpoint was added to this trial shortly after funding was obtained for the original AAA trial. As this additional endpoint has little to do with cardiovascular disease, funding was sought, and gained, from the Wellcome Trust. This end point was known as the ‘Randomised controlled trial of aspirin in the reduction of age associated cognitive decline’, and any information relating only to this endpoint will be headed with the title: ‘Cognitive decline endpoint’

The aim of this endpoint is to determine whether low dose aspirin treatment over a five-year period reduces cognitive decline in subjects at high risk of cardiovascular disease.

Ethics approval

AAA Trial:
1. Lanarkshire Research Ethics Committee: date of approval 22/04/1997 (ref: ER/4/97/8)
2. Greater Glasgow Community/Primary Care Local Research Ethics Committee: date of approval 14/06/1999 (ref: 45A/99)
3. Lothian Research Ethics Committee: date of approval 31/05/1999 (ref: 1702/99/3/23)

Cognitive Study:
1. Lanarkshire Research Ethics Committee: date of approval 26/10/1999 (ref: ER/49/10/99)
2. Greater Glasgow Community/Primary Care Local Research Ethics Committee: details as for AAA Trial (see above)
3. Lothian Research Ethics Committee: amendment to AAA Trial made and approved on 11/10/1999

Study design

Randomised, placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Cardiovascular disease, cognitive decline

Intervention

100 mg enteric-coated aspirin daily for five years or placebo daily for five years

The trials were initially designed to end simultaneously, but follow-up in the AAA Trial has been extended (with corresponding supplementary funding from BHF and CSO) to obtain the required number of major cardiovascular endpoints. Similar power considerations were not necessary for the cognitive decline endpoint; therefore the end date for the cognitive decline endpoint is 31st April 2006.

Public contact for the cognitive decline endpoint:
Dr Jackie Price
Community Health Sciences
University of Edinburgh Medical School
Teviot Place
Edinburgh
EH8 9AG
United Kingdom
Tel: +44 (0)131 650 3240
Fax: +44 (0)131 650 6904
Email: Jackie.Price@ed.ac.uk

Intervention type

Drug

Phase

Not Applicable

Drug names

Aspirin

Primary outcome measures

Myocardial infarction and stroke (fatal and non-fatal) or revascularisation

Cognitive decline endpoint:
A detailed battery of tests was administered to assess a broad range of the participants’ cognitive functions. The test battery was administered in a quiet room either in the clinic or at the patient’s home by a trained researcher. The order of tests in the battery was predetermined. The Mini Mental State Examination (MMSE) was included as a general mental assessment and as a ‘screen’ for dementia. Executive function was assessed with use of the Verbal Fluency Test, which requires participants to generate as many words as possible with a specified initial letter (C, F and L).

As a measure of non-verbal reasoning, participants were asked to work through all five sets (A to E) of the Raven’s Progressive Matrices, and were scored according to the number of items they completed correctly within 20 minutes. Immediate and delayed memory was assessed using a participant’s total score on the first five trials (I through V) of the Auditory Verbal Learning Test.

As a measure of mental flexibility, the Trail Making Test was administered and the time taken to complete part B was used in the subsequent analysis. In the Digit Symbol Test, used as a measure of speed of information processing, the number of symbols matched correctly to their corresponding numbers in 90 seconds was recorded.

The Hospital Anxiety and Depression Scale (HAD A and HAD D) was also used for the assessment of mood states, as these can affect performance on the tests, and the National Adult Reading Test (NART) was used to estimate Intelligence Quotient (IQ).

Secondary outcome measures

1. Total cardiovascular mortality
2. All cause mortality
3. Angina
4. Intermittent claudication
5. Transient ischaemic attack
6. Side effects/adverse events

Overall trial start date

01/04/1998

Overall trial end date

31/12/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Men and women aged between 50 and 80 years
2. Ankle brachial pressure index 0.95 or less in at least one limb
3. Living in central Scotland (Lothian, Greater Glasgow and Lanarkshire)
4. No history of clinical cardiovascular disease

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

3350 (recruitment ended as of 1st February 2002)

Participant exclusion criteria

1. Receiving aspirin and/or other anticoagulants
2. Contraindication to aspirin therapy

Recruitment start date

01/04/1998

Recruitment end date

31/12/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Wolfson Unit for Prevention of Peripheral Vascular Diseases
Edinburgh
EH8 9AG
United Kingdom

Sponsor information

Organisation

University of Edinburgh (UK)

Sponsor details

ACCORD Office
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

University/education

Website

http://www.ed.ac.uk/

Funders

Funder type

Charity

Funder name

British Heart Foundation (UK) (ref: RG/97006)

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Funder name

Chief Scientist Office (CSO) (UK) (ref: K/OPR/2/2/D320)

Alternative name(s)

CSO

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

United Kingdom

Funder name

Cognitive decline endpoint:

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Wellcome Trust (UK) (grant ref: 057762)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18762476
2. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20197530
3. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21223551

Publication citations

  1. Results

    Price JF, Stewart MC, Deary IJ, Murray GD, Sandercock P, Butcher I, Fowkes FG, , Low dose aspirin and cognitive function in middle aged to elderly adults: randomised controlled trial., BMJ, 2008, 337, a1198.

  2. Results

    Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, Sandercock PA, Fox KA, Lowe GD, Murray GD, , Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial., JAMA, 2010, 303, 9, 841-848, doi: 10.1001/jama.2010.221.

  3. Results

    Eborall HC, Stewart MC, Cunningham-Burley S, Price JF, Fowkes FG, Accrual and drop out in a primary prevention randomised controlled trial: qualitative study., Trials, 2011, 12, 7, doi: 10.1186/1745-6215-12-7.

Additional files

Editorial Notes