ASCEND: A study of cardiovascular events in diabetes

ISRCTN	ISRCTN60635500
DOI	https://doi.org/10.1186/ISRCTN60635500
ClinicalTrials.gov (NCT)	NCT00135226
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	341798
Protocol serial number	CTSU ASCEND 1
Sponsor	University of Oxford (UK)
Funder	British Heart Foundation

Submission date: 14/07/2005
Registration date: 01/09/2005
Last edited: 15/11/2024

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
ASCEND is a clinical trial which aimed to find out whether aspirin and/or omega-3 fatty acids (fish oils) reduced the risk of heart attacks and strokes in people with diabetes who did not already have any existing problems with their heart or blood circulation, when they started the study.
The main trial has now ended. Participants stopped taking study treatment in 2017, and results were reported in 2018. These main trial results showed that aspirin prevented serious vascular events (such as heart attacks and strokes) in these individuals, but the benefits were largely counterbalanced by an increase in major bleeds and there was no effect on the development of cancers.
ASCEND researchers continue to collect information on health outcomes by obtaining routinely collected data via central data registries and NHS sources. This Long-term Follow-up (LTFU) research will continue until 2037. The ASCEND researchers are especially interested in finding out whether taking aspirin protects against cancer, dementia/cognitive decline, or development of heart failure.
Additional information about this LTFU work is given on the study website: https://ascend.medsci.ox.ac.uk/about/long-term-study

Who can participate?
The original study participants were people who had diabetes, but did not already have cardiovascular disease. This is now a static cohort. Recruitment stopped in July 2011.

What does the study involve?
The ongoing Long-term Follow-up research is collecting Healthcare Systems Data (HSD) directly from NHS Custodians e.g. NHS England, NHS Wales (the Secure Anonymised Information Linkage Databank (SAIL), Digital Health and Care Wales (DHCW)), and NHS Scotland (Public Health Scotland (PHS) and the NHS Central Register (NHSCR)). Other Central Registries holding Healthcare Systems Data may also provide data. There is no further direct involvement for the participants.

What are the possible benefits and risks of participating?
Participants stopped study treatment in 2017 so there are no direct risks to them of the Long-term Follow-up research. All participants were informed of the main trial results in 2018. We are no longer in contact with the participants, but disseminate data about new results via the ASCEND website.

Where is the study run from?
The University of Oxford, managed by researchers at the Nuffield Department of Population Health (NDPH)

When is the study starting and how long is it expected to run for?
Participants were first recruited between June 2005 and July 2011. The main trial (when participants were on active treatment) ended in 2017. The Long-term Follow-up (via Healthcare Systems Data) will continue until 2037.

Who is funding the study?
Current funding is being provided by the British Heart Foundation (BHF).
In the past the study has received funding from: the BHF, Bayer Healthcare, Abbott Laboratories, Alzheimer’s Research UK, and the Macular Society.

Who is the main contact?
Professor Jane Armitage
ascend@ndph.ox.ac.uk

Contact information

Prof Jane Armitage
Scientific

ASCEND Office
CTSU, Nuffield Department of Population Health
Richard Doll Building
University of Oxford
Old Road Campus
Oxford
OX3 7LF
United Kingdom

ORCID ID	0000-0001-8691-9226
Phone	+44 (0)1865 743743
Email	ascend@ndph.ox.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Participant information sheet	ISRCTN60635500_EndOfStudyPIS_V1p0_16Nov2016.pdf
Scientific title	A randomised 2 x 2 factorial study of aspirin versus placebo, and of omega-3 fatty acid supplementation versus placebo, for primary prevention of cardiovascular events in people with diabetes
Study acronym	ASCEND
Study objectives	To determine whether 100 mg daily aspirin versus placebo and/or supplementation with 1 g daily omega-3 fatty acids or placebo prevents 'serious vascular events' (i.e. non-fatal heart attack, non-fatal stroke or death from vascular causes) in patients with diabetes who are not known to have occlusive arterial disease and to assess the effects on serious bleeding or other adverse events.
Ethics approval(s)	Approved 29/12/2003, North West - Haydock REC (previously North West Multi-centre Research Ethics Committee) (Barlow House, 4 Minshull St, Manchester, M1 3DZ, UK; +44 2071048138; haydock.rec@hra.nhs.uk), ref: 03/8/087
Health condition(s) or problem(s) studied	Diabetes (type 1 & 2)
Intervention	100 mg daily aspirin versus placebo and/or supplementation with 1 g daily omega-3 fatty acids or placebo.
Intervention type	Drug
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Aspirin, omega-3 fatty acids
Primary outcome measure(s)	Current primary outcome measure as of 15/11/2024: Long-term Follow-up Primary Outcome: The primary long-term efficacy assessment of aspirin will involve intention-to-treat comparisons among all randomized participants of the original allocation to aspirin versus placebo on the first occurrence of any incident gastrointestinal tract cancer. _____ Previous primary outcome measure as of 07/05/2019: 1. The primary efficacy assessments involve intention-to-treat comparisons among all randomized participants of allocation to aspirin versus placebo and, separately, of omega-3 fatty acids versus placebo on the first occurrence of any "Serious Vascular Event" (SVE), defined as: 1.1. Non-fatal myocardial infarction; or 1.2. Non-fatal stroke (excluding confirmed intracranial hemorrhage) or TIA; or 1.3. Vascular death excluding confirmed intracranial hemorrhage (defined as International Classification of Diseases 10th revision [ICD-10] I00-52 or I63-99, i.e. excluding subarachnoid hemorrhage [I60], intracerebral hemorrhage [I61], and other non-traumatic intracranial hemorrhage [I62]). Time frame: Randomised treatment phase during a mean of 7.4 years. 2. The primary safety assessments involve intention-to-treat comparisons among all randomized patients of allocation to aspirin versus placebo on the first occurrence of "any major bleed", defined as: 2.1. Any confirmed intracranial hemorrhage (including intracerebral, subarachnoid, subdural or any other intracranial hemorrhage); or 2.2. Sight-threatening eye bleeding; or 2.3. Any other serious bleeding episode Time frame: Randomised treatment phase during a mean of 7.4 years. _____ From 26/05/2016 to 07/05/2019: Effect of aspirin versus placebo and separately omega-3 fatty acids versus placebo on serious vascular events or TIA (defined as the combination of non-fatal myocardial infarction, non-fatal stroke or vascular death, excluding confirmed cerebral haemorrhage, or TIA) at the end of the scheduled treatment period (average of 7.5 years). _____ Original: The combination of non-fatal myocardial infarction, non-fatal stroke or vascular death, excluding confirmed cerebral haemorrhage
Key secondary outcome measure(s)	Current secondary outcome measures as of 15/11/2024: Long-term Follow-up Secondary Outcomes: Secondary long-term efficacy assessments of aspirin will involve intention-to-treat comparisons among all randomized participants of the original allocation to aspirin versus placebo on the first occurrence of: i. Any cancer (excluding non-fatal non-melanoma skin cancer); ii. Colorectal cancer; iii. Death from cancer; iv. Incident GI tract cancer by time since randomization: <3; ≥3 <5; ≥5 <10; ≥10 <20; ≥20 years _____ Previous secondary outcome measures as of 07/05/2019: 1. Secondary efficacy assessments involve intention-to-treat comparisons among all randomized participants of allocation to aspirin versus placebo and, separately, of omega-3 versus placebo on the first occurrence of the expanded vascular endpoint of "SVE or revascularization" (including coronary and non-coronary revascularizations). Time frame: Randomised treatment phase during a mean of 7.4 years 2. Secondary efficacy assessments of aspirin involve intention-to-treat comparisons during the scheduled treatment period among all randomized participants on the first occurrence of any incident gastrointestinal (GI) tract cancer (i.e. any GI cancer excluding pancreas and hepatobiliary), overall and after exclusion of the first three years of follow-up. Time frame: Randomised treatment phase during a mean of 7.4 years _____ From 26/05/2016 to 07/05/2019: 1. Effect of aspirin versus placebo and separately omega-3 fatty acids versus placebo on serious vascular events in various prognostic groups at the end of the scheduled treatment period (average of 7.5 years) 2. Effect of aspirin versus placebo and separately omega-3 fatty acids versus placebo on cerebral haemorrhage at the end of the scheduled treatment period (average of 7.5 years) _____ Original: 1. Serious vascular event in various prognostic subgroups 2. Cerebral haemorrhage
Completion date	31/07/2037

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	15000
Total final enrolment	15480
Key inclusion criteria	1. Male or female with diabetes (Type 1 or 2) 2. Aged greater than or equal to 40 years 3. No previous history of vascular disease 4. No clear contra-indication to aspirin 5. No other predominant life-threatening medical problem
Key exclusion criteria	The following point has been amended as of 11/02/2009: 2. Currently prescribed warfarin Initial information at time of registration: 1. Definite history of myocardial infarction, stroke or arterial revascularisation procedure 2. Currently prescribed aspirin, warfarin or any other blood thinning medication
Date of first enrolment	14/03/2005
Date of final enrolment	31/07/2011

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

ASCEND Office

CTSU, Nuffield Department of Population Health
Richard Doll Building
University of Oxford
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study will be available upon request. Procedures for accessing the data for this study are available at: https://www.ndph.ox.ac.uk/about/data-access-policy.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Baseline paper	01/04/2018	01/02/2019	Yes	No
Results article	Aspirin	18/10/2018	07/05/2019	Yes	No
Results article	n-3 fatty acids	18/10/2018	07/05/2019	Yes	No
Results article	Effect of low-dose aspirin on urinary 11-dehydro-thromboxane B2 in the ASCEND (A Study of Cardiovascular Events iN Diabetes) randomized controlled trial	04/03/2023	06/03/2023	Yes	No
Results article	Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data	03/06/2023	05/06/2023	Yes	No
Results article	ASCEND-Eye: Rationale, design and baseline characteristics for a sub-study of the ASCEND randomised trial	05/07/2023	25/09/2023	Yes	No
Results article	Effects of aspirin and omega-3 fatty acids on composite and subdomain scores from the NEI-VFQ-25 questionnaire: the ASCEND-Eye randomized controlled trial	05/11/2024	06/11/2024	Yes	No
Results article	ASCEND-Eye: Effects of Aspirin on Diabetic Retinopathy	01/07/2024	15/11/2024	Yes	No
Results article	ASCEND-Eye: Effects of Omega-3 Fatty Acids on Diabetic Retinopathy	01/05/2024	15/11/2024	Yes	No
Results article	Comparison of the Accuracy and Completeness of Records of Serious Vascular Events in Routinely Collected Data vs Clinical Trial-Adjudicated Direct Follow-up Data in the UK: Secondary Analysis of the ASCEND Randomized Clinical Trial	01/12/2021	15/11/2024	Yes	No
Results article	Decrements in health‐related quality of life associated with adverse events in people with diabetes	20/12/2021	15/11/2024	Yes	No
Results article	Effects of aspirin on dementia and cognitive function in diabetic patients: the ASCEND trial	01/06/2022	15/11/2024	Yes	No
Results article	Hospital costs associated with adverse events in people with diabetes in the UK	29/06/2022	15/11/2024	Yes	No
Results article	Thromboxane biosynthesis and future events in diabetes: the ASCEND trial	14/04/2024	15/11/2024	Yes	No
Other publications	recruitment methods	13/06/2016		Yes	No
Participant information sheet	version V1	16/11/2016	07/05/2019	No	Yes
Participant information sheet	version V8	12/10/2010	07/05/2019	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results				No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN60635500_PIS_V8p4_12Oct2010.pdf: Uploaded 07/05/2019
ISRCTN60635500_EndOfStudyPIS_V1p0_16Nov2016.pdf: Uploaded 07/05/2019

Editorial Notes

15/11/2024: The following changes were made to the trial record:
1. The IRAS number was added.
2. The primary outcome measure was changed.
3. The secondary outcome measures were changed.
4. The plain English summary was added.
5. The publication and dissemination plan was changed.
6. The contact email was changed.
7. The funders Bayer Schering Pharma AG (UK) and Solvay Pharmaceuticals GmbH (Germany) were removed.
8. Publication references added.
06/11/2024: Publication reference added.
25/09/2023: Publication reference added.
05/06/2023: Publication reference added.
06/03/2023: Publication reference added.
09/05/2019: The following changes were made to the trial record:
1. Publication and dissemination plan and IPD sharing statement added.
2. The overall trial end date was changed from 31/12/2017 to 31/07/2037.
07/05/2019: The following changes were made to the trial record:
1. The primary and secondary outcome measures were updated.
2. Added link to basic results (scientific).
3. Publication references added.
4. The total final enrolment number was added.
5. The participant information sheets have been uploaded.
01/02/2019: Publication reference added.
15/06/2016: Publication reference added.
11/02/2009: this record was updated to include amended trial dates. The initial trial dates at the time of registration were:
Initial overall trial start date: 01/03/2005
Initial overall trial end date: 01/03/2011