Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000613202
Ethics application status
Approved
Date submitted
29/06/2009
Date registered
22/07/2009
Date last updated
21/01/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Aspirin for the prevention of cognitive decline in the Elderly: a Neuro-Vascular Imaging Study (ENVIS-ion), a sub-study of ASPirin in Reducing Events in the Elderly (ASPREE)
Scientific title
A multi-centre, randomised, double-blind, placebo controlled trial of the effects of 100mg enteric-coated aspirin on rate of increase of magnetic resonance imaging(MRI)-based white matter hyperintensity (WMH) and silent brain infarction (SBI).
Secondary ID [1] 283947 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ENVIS-ion
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive decline in older adults 237113 0
Condition category
Condition code
Neurological 237441 237441 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Acetylsalicylic acid (aspirin) 100 mg; enteric coated unscored white tablet taken once per day for an average of 3 years
Intervention code [1] 236835 0
Treatment: Drugs
Comparator / control treatment
Placebo of acetylsalicylic acid; enteric coated unscored white tablet with identical appearance taken once per day for an average of 3 years enteric
Control group
Placebo

Outcomes
Primary outcome [1] 238242 0
Changes in brain magnetic resonance imaging (MRI) including white matter hyper intensity (WMH) and silent brain infarction (SBI) volumes.
Timepoint [1] 238242 0
3 years following randomisation
Primary outcome [2] 238243 0
Changes in retinal vascular imaging (RVI) parameters, including quantitatively measured retinal arteriolar and venular calibre and the presence of retinal arteriolar pathology.
Timepoint [2] 238243 0
3 years following randomisation
Secondary outcome [1] 244574 0
Death from any cause
Timepoint [1] 244574 0
3 years following randomisation
Secondary outcome [2] 244575 0
Incident dementia (defined according to the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV) criteria)
Timepoint [2] 244575 0
3 years following randomisation
Secondary outcome [3] 244576 0
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)
Timepoint [3] 244576 0
3 years following randomisation
Secondary outcome [4] 244577 0
Fatal and non-fatal cardiovascular events including:
1. Coronary heart disease death
2. Non-fatal myocardial infarction
3. Fatal and non-fatal stroke
4. Hospitalisation for heart failure
Timepoint [4] 244577 0
3 years following randomisation
Secondary outcome [5] 244578 0
Fatal and non-fatal cancer, excluding non-melanomatous skin cancer
Timepoint [5] 244578 0
3 years following randomisation
Secondary outcome [6] 244579 0
Cognitive decline as assessed by the following tests; Stoop test (Victoria version), Color Trails test, Digit Symbol Modalities (WAIS test), Modified Mini-Mental State Examination (3MS), Center for Epidemiologic Studies?Depression questionnaire (CES-D), Digit Symbol Substitution Test (DSST), Hopkins Verbal Learning Test?Revised (HVLT-R), Single Letter Fluency Test (SLFT).
Timepoint [6] 244579 0
3 years following randomisation
Secondary outcome [7] 244580 0
Major haemorrhagic events
Timepoint [7] 244580 0
3 years following randomisation

Eligibility
Key inclusion criteria
All subjects will be aged 70 years or more and capable of attending their usual family physician's clinic, providing informed consent and have no known contraindications to MRI.
Minimum age
70 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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 dementia
8. In addition those who lie outside of tolerance levels of 8-104% during placebo run-in phase will not be randomised
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
11. Absolute contraindications to undergo MRI

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Initially, the general practitioner (GP) is recruited into the study and with their consent their database is searched for possible participants. A mail-out database is created and letters are sent to all possible participants. Interested possible participants then phone the free-call ENVIS-ion telephone number and the trial nurse asks a set of telephone screening questions. Eligible participants then attend an initial screening visit (Visit 1) where consent is obtained and baseline measures are taken. Eligible participants are then asked to return to their GP for a GP screening visit. Within four weeks of Visit 1 eligible participants then attend a randomisation visit (Visit 2) where further baseline measures are collected and participants are randomised into one of the two treatment arms. Please note that until randomisation is complete participants may be excluded at anytime based on the exclusion criteria.
Following the completion of data collection at Visit 2, and if all inclusion criteria are satisfied, participants will be randomised to a treatment arm via the telephone or the internet. Telephone randomisation will be via a toll free 1800 Interactive Voice Response System (IVRS). For large clinical centers, randomisation will be achieved via the web portal. For both systems, password protected access is required for study personnel. Computer-generated medication numbers will be provided to trial sites through the IVRS or the web portal.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation list will be generated by an independent statistician. The randomisation list will be generated using the STATA “ralloc” procedure with randomisation stratified for site and age (<80 yrs and >=80 yrs). All staff remain blinded to treatment allocation through the randomisation procedure.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
30/06/2008
Actual
27/04/2010
Date of last participant enrolment
Anticipated
Actual
3/04/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
600
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,VIC
Recruitment hospital [1] 1983 0
The Canberra Hospital - Garran
Recruitment hospital [2] 1984 0
Royal Prince Alfred Hospital - Camperdown

Funding & Sponsors
Funding source category [1] 237225 0
Government body
Name [1] 237225 0
National Health and Medical Research Council (NHMRC) (ref: 471460)
Country [1] 237225 0
Australia
Primary sponsor type
University
Name
Australian National University (ANU)
Address
ANU Medical School
Frank Fenner Building 42
The Australian National University
Canberra ACT 0200
Country
Australia
Secondary sponsor category [1] 236716 0
University
Name [1] 236716 0
Monash University
Address [1] 236716 0
Research and Graduate Programs Office
Faculty of Medicine, Nursing and Health Sciences
PO Box 64
Monash University
Victoria 3800
Country [1] 236716 0
Australia
Other collaborator category [1] 731 0
Hospital
Name [1] 731 0
Clinical Trials Unit, Canberra Hospital
Address [1] 731 0
Building 1, Level 2
The Canberra Hospital
Po Box 11
Woden ACT 2606
Country [1] 731 0
Australia
Other collaborator category [2] 732 0
Other
Name [2] 732 0
Centre for Eye Research Australia
Address [2] 732 0
The University of Melbourne
32 Gisborne Street
Melbourne, Victoria 3002
Country [2] 732 0
Australia
Other collaborator category [3] 733 0
Hospital
Name [3] 733 0
Department of Radiology, The Alfred Hospital
Address [3] 733 0
P.O Box 315
Prahran. Victoria 3181
Country [3] 733 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239323 0
Australian National University (ANU)
Ethics committee address [1] 239323 0
Ethics committee country [1] 239323 0
Australia
Date submitted for ethics approval [1] 239323 0
24/04/2008
Approval date [1] 239323 0
30/04/2008
Ethics approval number [1] 239323 0
2008/115
Ethics committee name [2] 239324 0
ACT Health Human Research Ethics Committee
Ethics committee address [2] 239324 0
Ethics committee country [2] 239324 0
Australia
Date submitted for ethics approval [2] 239324 0
Approval date [2] 239324 0
11/02/2008
Ethics approval number [2] 239324 0
ETH.11/07.998
Ethics committee name [3] 239325 0
Monash University Human Research Ethics Committee
Ethics committee address [3] 239325 0
Ethics committee country [3] 239325 0
Australia
Date submitted for ethics approval [3] 239325 0
Approval date [3] 239325 0
14/05/2008
Ethics approval number [3] 239325 0
CF08/1314 - 2008000648
Ethics committee name [4] 239326 0
The Alfred Human Research Ethics Committee
Ethics committee address [4] 239326 0
Ethics committee country [4] 239326 0
Australia
Date submitted for ethics approval [4] 239326 0
Approval date [4] 239326 0
28/04/2008
Ethics approval number [4] 239326 0
79/08

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29811 0
Prof Walter Abhayaratna
Address 29811 0
Clinical Trials Unit, Building 1 Level 2 Canberra Hospital, Yamba Dr, GARRAN ACt 2605
Country 29811 0
Australia
Phone 29811 0
+61 2 6244 3687
Fax 29811 0
+61 2 6244 4647
Email 29811 0
[email protected]
Contact person for public queries
Name 13058 0
Ms Emily Wilford
Address 13058 0
Clinical Trials Unit
Building 1, Level 2
The Canberra Hospital
Po Box 11
Woden ACT 2606
Country 13058 0
Australia
Phone 13058 0
+61 2 6244 3687
Fax 13058 0
+61 2 6244 4647
Email 13058 0
[email protected]
Contact person for scientific queries
Name 3986 0
Professor Walter Abhayaratna
Address 3986 0
Clinical Trials Unit, Building 1, Level 2 Canberra Hospital, Yamba Dr, Garran ACT 2605
Country 3986 0
Australia
Phone 3986 0
+61 2 6244 3687
Fax 3986 0
+61 2 6244 4647
Email 3986 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseCovert Brain Infarction: Towards Precision Medicine in Research, Diagnosis, and Therapy for a Silent Pandemic.2020https://dx.doi.org/10.1161/STROKEAHA.120.030686
N.B. These documents automatically identified may not have been verified by the study sponsor.