ASCEND: A Study of Cardiovascular Events iN Diabetes

NCT ID: NCT00135226

Last Updated: 2025-05-28

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

15480 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-03-31

Study Completion Date

2037-07-31

Brief Summary

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The purpose of this study is to determine whether 100mg daily aspirin versus placebo and/or supplementation with 1 gram daily omega-3 fatty acids or placebo prevents "serious vascular events" (i.e. non-fatal heart attack, non-fatal stroke or transient ischaemic attack, 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.

Detailed Description

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The role of antiplatelet therapy (chiefly aspirin) for the secondary prevention of heart attacks and strokes is firmly established for many high-risk people with diagnosed arterial disease, and the proportional reductions in these cardiovascular events appear to be about one quarter, whether or not such patients have diabetes. But, most younger and middle-aged people with diabetes do not have manifest arterial disease - although they are still at significant cardiovascular risk - and yet few trials have tested aspirin in such individuals. As a result, there is substantial uncertainty about the role of aspirin for the prevention of heart attacks and strokes among apparently healthy people with diabetes, and only a small minority receives it.

There is consistent evidence from observational studies of lower rates of cardiovascular disease (particularly cardiac and sudden death) in people with higher intakes, or higher blood levels, of fish oils (omega-3 fatty acids). Trials in people who have survived a heart attack have shown modest, but potentially worthwhile, reductions in coronary events.

If ASCEND can reliably demonstrate that aspirin and/or fish oils safely reduce the risk of cardiovascular events and deaths in people with diabetes who do not have pre-existing arterial disease, then this would be relevant to some tens of millions of people world-wide (who are currently not receiving such therapy) and might save tens of thousands of lives each year.

The initial results (published 2018) showed that aspirin prevented serious vascular events in patients with diabetes who did not already have cardiovascular disease, but it caused almost as many major bleeds and there was no effect on cancers. There was no significant difference in the risk of serious vascular events between those who were assigned to receive n-3 fatty acid supplementation and those who were assigned to receive placebo.

ASCEND will be conducting long-term follow-up for 20-years beyond the scheduled treatment period (which ended in 2017). We will collect relevant data from UK central health registries. This will be used to assess whether the balance of benefits versus hazards of aspirin observed within the main trial, relating to major vascular events such as heart attack or stroke, continue long-term or whether additional benefits emerge during longer-term follow-up.

In addition ASCEND will use this long-term post-trial follow-up to investigate further whether low-dose aspirin might protect against cancer. The main cancer analyses is planned to take place \~5-years after the end of the treatment period.

Conditions

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Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Aspirin + Omega-3 Ethyl Esters

Participants receive 100mg of aspirin once daily and 1g of omega-3 ethyl esters once daily.

Group Type ACTIVE_COMPARATOR

Aspirin

Intervention Type DRUG

Omega-3 Ethyl Esters

Intervention Type DRUG

Aspirin + Placebo Omega-3 Ethyl Esters

Participants receive 100mg of aspirin once daily and placebo omega-3 ethyl esters once daily.

Group Type ACTIVE_COMPARATOR

Aspirin

Intervention Type DRUG

Placebo Omega-3 Ethyl Esters

Intervention Type DRUG

Placebo Aspirin + Omega-3 Ethyl Esters

Participants receive placebo aspirin once daily and 1g of omega-3 ethyl esters once daily.

Group Type ACTIVE_COMPARATOR

Omega-3 Ethyl Esters

Intervention Type DRUG

Placebo Aspirin

Intervention Type DRUG

Placebo Aspirin + Placebo Omega-3 Ethyl Esters

Participants receive placebo aspirin once daily and placebo omega-3 ethyl esters once daily.

Group Type ACTIVE_COMPARATOR

Placebo Aspirin

Intervention Type DRUG

Placebo Omega-3 Ethyl Esters

Intervention Type DRUG

Interventions

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Aspirin

Intervention Type DRUG

Omega-3 Ethyl Esters

Intervention Type DRUG

Placebo Aspirin

Intervention Type DRUG

Placebo Omega-3 Ethyl Esters

Intervention Type DRUG

Other Intervention Names

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n-3 fatty acid Omacor

Eligibility Criteria

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Inclusion Criteria

* Males or females with type 1 or type 2 diabetes mellitus.
* Aged ≥ 40 years.
* No previous history of vascular disease.
* No clear contra-indication to aspirin.
* No other predominant life-threatening medical problem.

Exclusion Criteria

* Definite history of myocardial infarction, stroke or arterial revascularisation procedure.
* Currently prescribed aspirin, warfarin or any other blood thinning medication.
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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British Heart Foundation

OTHER

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role collaborator

Medical Research Council

OTHER_GOV

Sponsor Role collaborator

Solvay Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Abbott

INDUSTRY

Sponsor Role collaborator

Mylan

UNKNOWN

Sponsor Role collaborator

Health Data Research UK

UNKNOWN

Sponsor Role collaborator

Alzheimer's Research UK

UNKNOWN

Sponsor Role collaborator

The Macular Society

UNKNOWN

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jane M Armitage, BSc, MBBS, MRCP, FFPH

Role: PRINCIPAL_INVESTIGATOR

Clinical Trial Service Unit, NDPH, University of Oxford

Locations

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Clinical Trial Service Unit, NDPH, University of Oxford

Oxford, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J. 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. JAMA Netw Open. 2021 Dec 1;4(12):e2139748. doi: 10.1001/jamanetworkopen.2021.39748.

Reference Type BACKGROUND
PMID: 34962561 (View on PubMed)

Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J. Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data. Heart. 2023 Sep 13;109(19):1467-1472. doi: 10.1136/heartjnl-2023-322616.

Reference Type BACKGROUND
PMID: 37270201 (View on PubMed)

Sammons E, Bowman L, Stevens W, Buck G, Wallendszus K, Hammami I, Parish S, Armitage J; ASCEND Collaborative Group. ASCEND-Eye: Rationale, design and baseline characteristics for a sub-study of the ASCEND randomised trial, exploring the effects of aspirin and omega-3 fatty acids on diabetic retinopathy and age-related macular degeneration. Contemp Clin Trials Commun. 2023 Jul 5;35:101184. doi: 10.1016/j.conctc.2023.101184. eCollection 2023 Oct.

Reference Type BACKGROUND
PMID: 37745288 (View on PubMed)

Parish S, Mafham M, Offer A, Barton J, Wallendszus K, Stevens W, Buck G, Haynes R, Collins R, Bowman L, Armitage J. Effects of aspirin on dementia and cognitive function in diabetic patients: the ASCEND trial. Eur Heart J. 2022 Jun 1;43(21):2010-2019. doi: 10.1093/eurheartj/ehac179.

Reference Type RESULT
PMID: 35393614 (View on PubMed)

Parish S, Mafham M, Offer A, Barton J, Wallendszus K, Stevens W, Buck G, Haynes R, Collins R, Bowman L, Armitage J; ASCEND Study Collaborative Group. Effects of Omega-3 Fatty Acid Supplements on Arrhythmias. Circulation. 2020 Jan 28;141(4):331-333. doi: 10.1161/CIRCULATIONAHA.119.044165. Epub 2020 Jan 27. No abstract available.

Reference Type RESULT
PMID: 31986094 (View on PubMed)

ASCEND Study Collaborative Group; Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018 Oct 18;379(16):1529-1539. doi: 10.1056/NEJMoa1804988. Epub 2018 Aug 26.

Reference Type RESULT
PMID: 30146931 (View on PubMed)

ASCEND Study Collaborative Group; Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med. 2018 Oct 18;379(16):1540-1550. doi: 10.1056/NEJMoa1804989. Epub 2018 Aug 26.

Reference Type RESULT
PMID: 30146932 (View on PubMed)

Bowman L, Mafham M, Stevens W, Haynes R, Aung T, Chen F, Buck G, Collins R, Armitage J; ASCEND Study Collaborative Group. ASCEND: A Study of Cardiovascular Events iN Diabetes: Characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes. Am Heart J. 2018 Apr;198:135-144. doi: 10.1016/j.ahj.2017.12.006. Epub 2017 Dec 24.

Reference Type RESULT
PMID: 29653635 (View on PubMed)

Sammons EL, Buck G, Bowman LJ, Stevens WM, Hammami I, Parish S, Armitage J; ASCEND Study Collaborative Group. ASCEND-Eye: Effects of Omega-3 Fatty Acids on Diabetic Retinopathy. Ophthalmology. 2024 May;131(5):526-533. doi: 10.1016/j.ophtha.2023.11.030. Epub 2023 Dec 3.

Reference Type RESULT
PMID: 38052385 (View on PubMed)

Sammons EL, Buck G, Bowman LJ, Stevens WM, Hammami I, Parish S, Armitage J; ASCEND Study Collaborative Group. ASCEND-Eye: Effects of Aspirin on Diabetic Retinopathy. Ophthalmology. 2024 Jul;131(7):771-779. doi: 10.1016/j.ophtha.2024.01.018. Epub 2024 Jan 17.

Reference Type RESULT
PMID: 38237868 (View on PubMed)

Petrucci G, Buck GA, Rocca B, Parish S, Baigent C, Hatem D, Mafham M, Habib A, Bowman L, Armitage J, Patrono C. Thromboxane biosynthesis and future events in diabetes: the ASCEND trial. Eur Heart J. 2024 Apr 14;45(15):1355-1367. doi: 10.1093/eurheartj/ehad868.

Reference Type RESULT
PMID: 38385506 (View on PubMed)

Sammons E, Bowman L, Stevens W, Buck G, Hammami I, Parish S, Armitage J; ASCEND-Eye Collaborative Group. Effects of aspirin and omega-3 fatty acids on age-related macular degeneration in ASCEND-Eye: a randomised placebo-controlled trial in a population with diabetes. BMJ Open. 2025 Feb 26;15(2):e090605. doi: 10.1136/bmjopen-2024-090605.

Reference Type RESULT
PMID: 40010818 (View on PubMed)

Sammons EL, Buck G, Bowman LJ, Stevens WM, Hammami I, Parish S, Armitage J; ASCEND Study Collaborative Group. 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. BMC Ophthalmol. 2024 Nov 5;24(1):481. doi: 10.1186/s12886-024-03741-x.

Reference Type RESULT
PMID: 39501183 (View on PubMed)

Parish S, Buck G, Aung T, Mafham M, Clark S, Hill MR, Collins R, Bowman L, Armitage J; ASCEND Study Collaborative Group. Effect of low-dose aspirin on urinary 11-dehydro-thromboxane B2 in the ASCEND (A Study of Cardiovascular Events iN Diabetes) randomized controlled trial. Trials. 2023 Mar 4;24(1):166. doi: 10.1186/s13063-023-07198-z.

Reference Type DERIVED
PMID: 36871000 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.ctsu.ox.ac.uk/research/ascend

The study website for information about ASCEND: A Study of Cardiovascular Events iN Diabetes

Other Identifiers

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60635500

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTSUASCEND1

Identifier Type: -

Identifier Source: org_study_id

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