Diabetes MellitusPhase 4NCT00135226
ASCEND: A Study of Cardiovascular Events iN Diabetes
A Phase 4 study testing Aspirin and Omega-3 Ethyl Esters in people with Diabetes Mellitus, run by University of Oxford at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Aspirin and Omega-3 Ethyl Esters
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15,480 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2005to 31 Jul 2037
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Definite history of myocardial infarction, stroke or arterial revascularisation procedure.
- Currently prescribed aspirin, warfarin or any other blood thinning medication.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Trial Service Unit, NDPH, University of Oxford
Oxford, OX3 7LF
About this study
Official title: A Study of Cardiovascular Events iN Diabetes - A Randomized 2x2 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
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.
Read the detailed description
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
- Diabetes Mellitus
- Being tested
- Aspirin, Omega-3 Ethyl Esters, Placebo Aspirin, Placebo Omega-3 Ethyl Esters
- Keywords
- Diabetes Mellitus, Cardiovascular Disease, Aspirin, Omega-3 fatty acids, Primary prevention, Randomized Controlled Trial, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, n-3 fatty acid
- Medical subject headings
- Diabetes Mellitus, Cardiovascular Diseases, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Omega-3 Ethyl EstersDrug
Also called n-3 fatty acid, Omacor
Placebo AspirinDrug
Placebo Omega-3 Ethyl EstersDrug
| Study group | Role | What they receive |
|---|---|---|
| Aspirin + Omega-3 Ethyl Esters | Active comparator | Participants receive 100mg of aspirin once daily and 1g of omega-3 ethyl esters once daily. Receives: Drug: Aspirin; Drug: Omega-3 Ethyl Esters |
| Aspirin + Placebo Omega-3 Ethyl Esters | Active comparator | Participants receive 100mg of aspirin once daily and placebo omega-3 ethyl esters once daily. Receives: Drug: Aspirin; Drug: Placebo Omega-3 Ethyl Esters |
| Placebo Aspirin + Omega-3 Ethyl Esters | Active comparator | Participants receive placebo aspirin once daily and 1g of omega-3 ethyl esters once daily. Receives: Drug: Omega-3 Ethyl Esters; Drug: Placebo Aspirin |
| Placebo Aspirin + Placebo Omega-3 Ethyl Esters | Active comparator | Participants receive placebo aspirin once daily and placebo omega-3 ethyl esters once daily. Receives: Drug: Placebo Aspirin; Drug: Placebo Omega-3 Ethyl Esters |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With First Occurrence of Any Serious Vascular Event (SVE)
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:
- non-fatal myocardial infarction; or
- non-fatal stroke (excluding confirmed intracranial hemorrhage) or TIA; or
- 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]).
Measured: Randomized treatment phase during a mean of 7.4 years
Number of Participants With First Occurrence of Any Major Bleed (Aspirin Comparison Only)
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:
- any confirmed intracranial hemorrhage (including intracerebral, subarachnoid, subdural or any other intracranial hemorrhage); or
- sight-threatening eye bleeding; or
- any other serious bleeding episode.
Measured: Randomized treatment phase during a mean of 7.4 years
Secondary outcomes (2)
Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations
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).
Measured: Randomized treatment phase during a mean of 7.4 years
Number of Participants With Any Incident Gastrointestinal (GI) Tract Cancer (Aspirin Comparison Only)
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.
Measured: Randomized treatment phase during a mean of 7.4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2005 (estimated)
- Study startMar 2005
- Primary completion12 Mar 2018
- Study completion31 Jul 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15,480 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, Bayer, Medical Research Council, Solvay Pharmaceuticals, Abbott, Mylan, Health Data Research UK, Alzheimer's Research UK, The Macular Society
- Responsible party
- Sponsor
- Investigators
- Jane M Armitage, BSc, MBBS, MRCP, FFPH, Principal investigator, Clinical Trial Service Unit, NDPH, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00135226
- Sponsor's protocol ID
- CTSUASCEND1
- Other IDs
- 60635500
- Status last verified
- May 2025
- First submitted
- 24 Aug 2005
- Last updated
- 28 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: Proposals for substudies must be approved by the Steering Committee. Procedures for accessing the data for this study are available on: https://www.ndph.ox.ac.uk/about/data-access-policy.
Publications
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.
PubMed 34962561Harper 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.
PubMed 37270201Sammons 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.
PubMed 37745288Parish 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.
PubMed 35393614Parish 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.
PubMed 31986094ASCEND 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.
PubMed 30146931ASCEND 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.
PubMed 30146932Bowman 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.
PubMed 29653635Sammons 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.
PubMed 38052385Sammons 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.
PubMed 38237868Petrucci 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.
PubMed 38385506Sammons 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.
PubMed 40010818Sammons 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.
PubMed 39501183Parish 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.
PubMed 36871000