ASCEND: A Study of Cardiovascular Events iN Diabetes

Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00135226
• Other study ID #: CTSUASCEND1
• Secondary ID: 60635500
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: March 2005
• Est. completion date: July 31, 2037

Study information

• Verified date: December 2023
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15480
• Est. completion date: July 31, 2037
• Est. primary completion date: March 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

Drug:
• Aspirin

• Omega-3 Ethyl Esters

• Placebo Aspirin

• Placebo Omega-3 Ethyl Esters

Locations

Country	Name	City	State
United Kingdom	Clinical Trial Service Unit, NDPH, University of Oxford	Oxford

Sponsors (10)

Lead Sponsor	Collaborator
University of Oxford	Abbott, Alzheimer's Research UK, Bayer, British Heart Foundation, Health Data Research UK, Medical Research Council, Mylan, Solvay Pharmaceuticals, The Macular Society

Country where clinical trial is conducted

United Kingdom, 

References & Publications (9)

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, Pe — View 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, Pe — View 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 supp — View 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. — View 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. — View 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 — View 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: 1 — View 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. — View 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. 2023 Dec 3:S0161-6420(23)00870-9. doi: 10.1016/j.ophtha.2023.1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Fatal Event: All-cause Mortality	'All-cause mortality' includes all recorded deaths.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Fatal Event: Coronary	Fatal 'Coronary' events include deaths from: Acute MI and other CHD (unspecified Acute ischaemic heart disease; Atherosclerotic heart disease; Ischaemic cardiomyopathy; unspecified Chronic ischaemic heart disease).	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Fatal Event: All Stroke	Fatal 'All stroke' events include deaths from: Haemorrhagic stroke (Intracerebral haemorrhage; Subarachnoid haemorrhage); Non-haemorrhagic stroke (Cerebral infarction; Stroke not specified as haemorrhage or infarction).	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Fatal Event: Other Vascular	Fatal 'Other vascular' events include deaths from: Heart failure (excluding ischaemic cardiomyopathy); Other vascular death (excluding stroke; and Cardiac death (excluding CHD).	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Fatal Event: Cancer	Fatal 'Cancer' events include any death attributed to cancer.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Fatal Event: Respiratory	Fatal 'Respiratory' events include any death attributed to respiratory causes.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Fatal Event: Other Medical	Fatal 'Other medical' events include deaths from: Non-vascular medical causes (excluding cancer and respiratory, including Fatal GI bleed or perforation); and deaths from Renal disease and Diabetes.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Fatal Event: External Cause	Fatal 'External cause' events include deaths from: Injury; Fracture; Self harm; and Medical and surgical complications	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Fatal Event: Unknown Cause	Any death for which the cause is not known.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Any Cancer	Incidence of fatal or non-fatal cancers. Any cancer excludes non-fatal non-melanoma skin cancer and non-fatal recurrence of a cancer that had occurred before randomization.; A single participant may have had multiple cancers.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Other Gastrointestinal Cancer (Aspirin Comparison Only)	Includes fatal and non-fatal cancers. Excludes cancers reported in the gastrointestinal tract category (see secondary outcome measure #4), and includes hepatobiliary and pancreatic cancers.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Respiratory Cancer	Includes fatal and non-fatal cancers. Includes lung and larynx cancer.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Genitourinary Cancer	Includes fatal and non-fatal renal, bladder, prostate, gynaecological and other GU cancers	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Hematological Cancer	Includes fatal and non-fatal cancers. Includes leukaemia and lymphoma.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Breast Cancer	Includes fatal and non-fatal cancers.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Melanoma	Includes fatal and non-fatal melanomas.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Other Cancer	Includes fatal and non-fatal cancers not included elsewhere (where the type of cancer is known).	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Unspecified Cancer	Includes fatal and non-fatal cancers of unknown type.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Atrial Fibrillation (Omega-3 Comparison Only)	Includes fatal and non-fatal events.	Randomized treatment phase during a mean of 7.4 years
Other	Number of Participants With Event: Other Arrhythmia (Omega-3 Comparison Only)	Includes fatal and non-fatal events, excludes atrial fibrillation.	Randomized treatment phase during a mean of 7.4 years
Primary	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]).	Randomized treatment phase during a mean of 7.4 years
Primary	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.	Randomized treatment phase during a mean of 7.4 years
Secondary	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).	Randomized treatment phase during a mean of 7.4 years
Secondary	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.	Randomized treatment phase during a mean of 7.4 years

External Links

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