Clinical trial NCT00135226: ASCEND: A Study of Cardiovascular Events iN Diabetes
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Diabetes Mellitus
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
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
name: Bayer
name: Medical Research Council
name: Solvay Pharmaceuticals
name: Abbott
name: Mylan
name: Health Data Research UK
name: Alzheimer's Research UK
name: The Macular Society
First posted: 2005-08-25
Enrollment: 15480
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief 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. 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With First Occurrence of Any Serious Vascular Event (SVE)
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With First Occurrence of Any Major Bleed (Aspirin Comparison Only)
timeFrame: Randomized treatment phase during a mean of 7.4 years
Secondary outcomes:
measure: Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Any Incident Gastrointestinal (GI) Tract Cancer (Aspirin Comparison Only)
timeFrame: Randomized treatment phase during a mean of 7.4 years
Other outcomes:
measure: Number of Participants With Fatal Event: All-cause Mortality
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Fatal Event: Coronary
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Fatal Event: All Stroke
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Fatal Event: Other Vascular
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Fatal Event: Cancer
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Fatal Event: Respiratory
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Fatal Event: Other Medical
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Fatal Event: External Cause
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Fatal Event: Unknown Cause
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Any Cancer
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Other Gastrointestinal Cancer (Aspirin Comparison Only)
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Respiratory Cancer
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Genitourinary Cancer
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Hematological Cancer
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Breast Cancer
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Melanoma
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Other Cancer
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Unspecified Cancer
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Atrial Fibrillation (Omega-3 Comparison Only)
timeFrame: Randomized treatment phase during a mean of 7.4 years
measure: Number of Participants With Event: Other Arrhythmia (Omega-3 Comparison Only)
timeFrame: Randomized treatment phase during a mean of 7.4 years
Locations:
city: Oxford
country: United Kingdom
facility: Clinical Trial Service Unit, NDPH, University of Oxford
Study officials:
affiliation: Clinical Trial Service Unit, NDPH, University of Oxford
name: Jane M Armitage, BSc, MBBS, MRCP, FFPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.