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NCT Number: NCT00135226

ASCEND: A Study of Cardiovascular Events iN 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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Diabetes Mellitus Autoimmune Diseases Cardiovascular Diseases Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Clinical Trial Service Unit, NDPH, University of Oxford

Oxford, OX3 7LF, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Aspirin

Drug

Omega-3 Ethyl Esters

Drug

Other names: n-3 fatty acid, Omacor

Placebo Aspirin

Drug

Placebo Omega-3 Ethyl Esters

Drug

Primary outcomes

  1. Number of Participants With First Occurrence of Any Serious Vascular Event (SVE)

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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]).

  2. Number of Participants With First Occurrence of Any Major Bleed (Aspirin Comparison Only)

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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.

Secondary outcomes

  1. Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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).

  2. Number of Participants With Any Incident Gastrointestinal (GI) Tract Cancer (Aspirin Comparison Only)

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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.

Other outcomes

  1. Number of Participants With Fatal Event: All-cause Mortality

    Time frame: Randomized treatment phase during a mean of 7.4 years

    'All-cause mortality' includes all recorded deaths.

  2. Number of Participants With Fatal Event: Coronary

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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).

  3. Number of Participants With Fatal Event: All Stroke

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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).

  4. Number of Participants With Fatal Event: Other Vascular

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Fatal 'Other vascular' events include deaths from: Heart failure (excluding ischaemic cardiomyopathy); Other vascular death (excluding stroke; and Cardiac death (excluding CHD).

  5. Number of Participants With Fatal Event: Cancer

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Fatal 'Cancer' events include any death attributed to cancer.

  6. Number of Participants With Fatal Event: Respiratory

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Fatal 'Respiratory' events include any death attributed to respiratory causes.

  7. Number of Participants With Fatal Event: Other Medical

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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.

  8. Number of Participants With Fatal Event: External Cause

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Fatal 'External cause' events include deaths from: Injury; Fracture; Self harm; and Medical and surgical complications

  9. Number of Participants With Fatal Event: Unknown Cause

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Any death for which the cause is not known.

  10. Number of Participants With Event: Any Cancer

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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.

  11. Number of Participants With Event: Other Gastrointestinal Cancer (Aspirin Comparison Only)

    Time frame: Randomized treatment phase during a mean of 7.4 years

    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.

  12. Number of Participants With Event: Respiratory Cancer

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal cancers. Includes lung and larynx cancer.

  13. Number of Participants With Event: Genitourinary Cancer

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal renal, bladder, prostate, gynaecological and other GU cancers

  14. Number of Participants With Event: Hematological Cancer

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal cancers. Includes leukaemia and lymphoma.

  15. Number of Participants With Event: Breast Cancer

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal cancers.

  16. Number of Participants With Event: Melanoma

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal melanomas.

  17. Number of Participants With Event: Other Cancer

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal cancers not included elsewhere (where the type of cancer is known).

  18. Number of Participants With Event: Unspecified Cancer

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal cancers of unknown type.

  19. Number of Participants With Event: Atrial Fibrillation (Omega-3 Comparison Only)

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal events.

  20. Number of Participants With Event: Other Arrhythmia (Omega-3 Comparison Only)

    Time frame: Randomized treatment phase during a mean of 7.4 years

    Includes fatal and non-fatal events, excludes atrial fibrillation.

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Collaborators

  • Abbott
  • Alzheimer's Research UK
  • Bayer
  • British Heart Foundation
  • Health Data Research UK
  • Medical Research Council
  • Mylan
  • Solvay Pharmaceuticals
  • The Macular Society

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2018
Study completion
2037
First posted
Aug 25, 2005
Registry last updated
May 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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