Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

ASCEND: A Study of Cardiovascular Events iN Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00135226
Recruitment Status : Active, not recruiting
First Posted : August 25, 2005
Results First Posted : April 26, 2019
Last Update Posted : April 26, 2019
Sponsor:
Collaborators:
British Heart Foundation
Bayer
EPD Solutions, A Philips Company
Medical Research Council
Information provided by (Responsible Party):
University of Oxford

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Drug: Aspirin Drug: Omega-3 Ethyl Esters Drug: Placebo Aspirin Drug: Placebo Omega-3 Ethyl Esters Phase 4

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. There have been, however, no large-scale trials of the use of fish oils for the prevention of vascular events in people without diagnosed arterial disease.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15480 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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 Start Date : March 2005
Actual Primary Completion Date : March 12, 2018
Estimated Study Completion Date : July 31, 2037

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Aspirin + Omega-3 Ethyl Esters
Participants receive 100mg of aspirin once daily and 1g of omega-3 ethyl esters once daily.
Drug: Aspirin
Drug: Omega-3 Ethyl Esters
Other Names:
  • n-3 fatty acid
  • Omacor

Active Comparator: Aspirin + Placebo Omega-3 Ethyl Esters
Participants receive 100mg of aspirin once daily and placebo omega-3 ethyl esters once daily.
Drug: Aspirin
Drug: Placebo Omega-3 Ethyl Esters
Active Comparator: Placebo Aspirin + Omega-3 Ethyl Esters
Participants receive placebo aspirin once daily and 1g of omega-3 ethyl esters once daily.
Drug: Omega-3 Ethyl Esters
Other Names:
  • n-3 fatty acid
  • Omacor

Drug: Placebo Aspirin
Active Comparator: Placebo Aspirin + Placebo Omega-3 Ethyl Esters
Participants receive placebo aspirin once daily and placebo omega-3 ethyl esters once daily.
Drug: Placebo Aspirin
Drug: Placebo Omega-3 Ethyl Esters



Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00135226


Locations
Layout table for location information
United Kingdom
Clinical Trial Service Unit, University of Oxford
Oxford, United Kingdom, OX3 7LF
Sponsors and Collaborators
University of Oxford
British Heart Foundation
Bayer
EPD Solutions, A Philips Company
Medical Research Council
Investigators
Layout table for investigator information
Principal Investigator: Jane M Armitage, BSc, MBBS, MRCP, FFPH Clinical Trial Service Unit, University of Oxford
  Study Documents (Full-Text)

Documents provided by University of Oxford:
Statistical Analysis Plan  [PDF] July 23, 2018


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT00135226    
Other Study ID Numbers: CTSUASCEND1
60635500 ( Registry Identifier: ISRCTN )
First Posted: August 25, 2005    Key Record Dates
Results First Posted: April 26, 2019
Last Update Posted: April 26, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Access Criteria: See URL
URL: https://www.ndph.ox.ac.uk/about/data-access-policy
Keywords provided by University of Oxford:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics