ASCEND: A study of cardiovascular events in diabetes
| ISRCTN | ISRCTN60635500 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN60635500 |
| IRAS number | 341798 |
| ClinicalTrials.gov number | NCT00135226 |
| Secondary identifying numbers | CTSU ASCEND 1 |
- Submission date
- 14/07/2005
- Registration date
- 01/09/2005
- Last edited
- 15/11/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
ASCEND is a clinical trial which aimed to find out whether aspirin and/or omega-3 fatty acids (fish oils) reduced the risk of heart attacks and strokes in people with diabetes who did not already have any existing problems with their heart or blood circulation, when they started the study.
The main trial has now ended. Participants stopped taking study treatment in 2017, and results were reported in 2018. These main trial results showed that aspirin prevented serious vascular events (such as heart attacks and strokes) in these individuals, but the benefits were largely counterbalanced by an increase in major bleeds and there was no effect on the development of cancers.
ASCEND researchers continue to collect information on health outcomes by obtaining routinely collected data via central data registries and NHS sources. This Long-term Follow-up (LTFU) research will continue until 2037. The ASCEND researchers are especially interested in finding out whether taking aspirin protects against cancer, dementia/cognitive decline, or development of heart failure.
Additional information about this LTFU work is given on the study website: https://ascend.medsci.ox.ac.uk/about/long-term-study
Who can participate?
The original study participants were people who had diabetes, but did not already have cardiovascular disease. This is now a static cohort. Recruitment stopped in July 2011.
What does the study involve?
The ongoing Long-term Follow-up research is collecting Healthcare Systems Data (HSD) directly from NHS Custodians e.g. NHS England, NHS Wales (the Secure Anonymised Information Linkage Databank (SAIL), Digital Health and Care Wales (DHCW)), and NHS Scotland (Public Health Scotland (PHS) and the NHS Central Register (NHSCR)). Other Central Registries holding Healthcare Systems Data may also provide data. There is no further direct involvement for the participants.
What are the possible benefits and risks of participating?
Participants stopped study treatment in 2017 so there are no direct risks to them of the Long-term Follow-up research. All participants were informed of the main trial results in 2018. We are no longer in contact with the participants, but disseminate data about new results via the ASCEND website.
Where is the study run from?
The University of Oxford, managed by researchers at the Nuffield Department of Population Health (NDPH)
When is the study starting and how long is it expected to run for?
Participants were first recruited between June 2005 and July 2011. The main trial (when participants were on active treatment) ended in 2017. The Long-term Follow-up (via Healthcare Systems Data) will continue until 2037.
Who is funding the study?
Current funding is being provided by the British Heart Foundation (BHF).
In the past the study has received funding from: the BHF, Bayer Healthcare, Abbott Laboratories, Alzheimer’s Research UK, and the Macular Society.
Who is the main contact?
Professor Jane Armitage
ascend@ndph.ox.ac.uk
Contact information
Scientific
ASCEND Office
CTSU, Nuffield Department of Population Health
Richard Doll Building
University of Oxford
Old Road Campus
Oxford
OX3 7LF
United Kingdom
 ORCID ID |
0000-0001-8691-9226 |
|---|---|
| Phone | +44 (0)1865 743743 |
| ascend@ndph.ox.ac.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Home |
| Study type | Prevention |
| Participant information sheet | ISRCTN60635500_EndOfStudyPIS_V1p0_16Nov2016.pdf |
| Scientific title | A randomised 2 x 2 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 acronym | ASCEND |
| Study hypothesis | To determine whether 100 mg daily aspirin versus placebo and/or supplementation with 1 g daily omega-3 fatty acids or placebo prevents 'serious vascular events' (i.e. non-fatal heart attack, non-fatal stroke 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. |
| Ethics approval(s) | Approved 29/12/2003, North West - Haydock REC (previously North West Multi-centre Research Ethics Committee) (Barlow House, 4 Minshull St, Manchester, M1 3DZ, UK; +44 2071048138; haydock.rec@hra.nhs.uk), ref: 03/8/087 |
| Condition | Diabetes (type 1 & 2) |
| Intervention | 100 mg daily aspirin versus placebo and/or supplementation with 1 g daily omega-3 fatty acids or placebo. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Aspirin, omega-3 fatty acids |
| Primary outcome measure | Current primary outcome measure as of 15/11/2024: Long-term Follow-up Primary Outcome: The primary long-term efficacy assessment of aspirin will involve intention-to-treat comparisons among all randomized participants of the original allocation to aspirin versus placebo on the first occurrence of any incident gastrointestinal tract cancer. _____ Previous primary outcome measure as of 07/05/2019: 1. 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: 1.1. Non-fatal myocardial infarction; or 1.2. Non-fatal stroke (excluding confirmed intracranial hemorrhage) or TIA; or 1.3. 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]). Time frame: Randomised treatment phase during a mean of 7.4 years. 2. 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: 2.1. Any confirmed intracranial hemorrhage (including intracerebral, subarachnoid, subdural or any other intracranial hemorrhage); or 2.2. Sight-threatening eye bleeding; or 2.3. Any other serious bleeding episode Time frame: Randomised treatment phase during a mean of 7.4 years. _____ From 26/05/2016 to 07/05/2019: Effect of aspirin versus placebo and separately omega-3 fatty acids versus placebo on serious vascular events or TIA (defined as the combination of non-fatal myocardial infarction, non-fatal stroke or vascular death, excluding confirmed cerebral haemorrhage, or TIA) at the end of the scheduled treatment period (average of 7.5 years). _____ Original: The combination of non-fatal myocardial infarction, non-fatal stroke or vascular death, excluding confirmed cerebral haemorrhage |
| Secondary outcome measures | Current secondary outcome measures as of 15/11/2024: Long-term Follow-up Secondary Outcomes: Secondary long-term efficacy assessments of aspirin will involve intention-to-treat comparisons among all randomized participants of the original allocation to aspirin versus placebo on the first occurrence of: i. Any cancer (excluding non-fatal non-melanoma skin cancer); ii. Colorectal cancer; iii. Death from cancer; iv. Incident GI tract cancer by time since randomization: <3; ≥3 <5; ≥5 <10; ≥10 <20; ≥20 years _____ Previous secondary outcome measures as of 07/05/2019: 1. 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). Time frame: Randomised treatment phase during a mean of 7.4 years 2. 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. Time frame: Randomised treatment phase during a mean of 7.4 years _____ From 26/05/2016 to 07/05/2019: 1. Effect of aspirin versus placebo and separately omega-3 fatty acids versus placebo on serious vascular events in various prognostic groups at the end of the scheduled treatment period (average of 7.5 years) 2. Effect of aspirin versus placebo and separately omega-3 fatty acids versus placebo on cerebral haemorrhage at the end of the scheduled treatment period (average of 7.5 years) _____ Original: 1. Serious vascular event in various prognostic subgroups 2. Cerebral haemorrhage |
| Overall study start date | 14/03/2005 |
| Overall study end date | 31/07/2037 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 15,000 |
| Total final enrolment | 15480 |
| Participant inclusion criteria | 1. Male or female with diabetes (Type 1 or 2) 2. Aged greater than or equal to 40 years 3. No previous history of vascular disease 4. No clear contra-indication to aspirin 5. No other predominant life-threatening medical problem |
| Participant exclusion criteria | The following point has been amended as of 11/02/2009: 2. Currently prescribed warfarin Initial information at time of registration: 1. Definite history of myocardial infarction, stroke or arterial revascularisation procedure 2. Currently prescribed aspirin, warfarin or any other blood thinning medication |
| Recruitment start date | 14/03/2005 |
| Recruitment end date | 31/07/2011 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Richard Doll Building
University of Oxford
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LF
United Kingdom
Sponsor information
University/education
Research Governance Ethics & Assurance (RGEA)
University of Oxford
Boundary Brook House
Churchill Drive
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 (0)1865 289855 |
|---|---|
| RGEA.Sponsor@admin.ox.ac.uk | |
| Website | https://researchsupport.admin.ox.ac.uk/contacts/rgea |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Industry
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- the_bhf, The British Heart Foundation, BHF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Current publication and dissemination plan as of 15/11/2024: The initial ASCEND results were published in 2018. Long-term Follow-up work is ongoing and publications for this are next planned in 2025/2026. Other ongoing work is being published regularly (see Study Outputs section). Results are also available on the study website https://ascend.medsci.ox.ac.uk/ _____ Previous publication and dissemination plan: Planned publication in a high-impact peer reviewed journal in 2038. Results will also be available on the study website https://ascend.medsci.ox.ac.uk/ |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request. Procedures for accessing the data for this study are available at: https://www.ndph.ox.ac.uk/about/data-access-policy. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Other publications | recruitment methods | 13/06/2016 | Yes | No | |
| Results article | Baseline paper | 01/04/2018 | 01/02/2019 | Yes | No |
| Participant information sheet | version V1 | 16/11/2016 | 07/05/2019 | No | Yes |
| Participant information sheet | version V8 | 12/10/2010 | 07/05/2019 | No | Yes |
| Results article | Aspirin | 18/10/2018 | 07/05/2019 | Yes | No |
| Results article | n-3 fatty acids | 18/10/2018 | 07/05/2019 | Yes | No |
| Results article | Effect of low-dose aspirin on urinary 11-dehydro-thromboxane B2 in the ASCEND (A Study of Cardiovascular Events iN Diabetes) randomized controlled trial | 04/03/2023 | 06/03/2023 | Yes | No |
| Results article | Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data | 03/06/2023 | 05/06/2023 | Yes | No |
| Results article | ASCEND-Eye: Rationale, design and baseline characteristics for a sub-study of the ASCEND randomised trial | 05/07/2023 | 25/09/2023 | Yes | No |
| Results article | 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 | 05/11/2024 | 06/11/2024 | Yes | No |
| Results article | ASCEND-Eye: Effects of Aspirin on Diabetic Retinopathy | 01/07/2024 | 15/11/2024 | Yes | No |
| Results article | ASCEND-Eye: Effects of Omega-3 Fatty Acids on Diabetic Retinopathy | 01/05/2024 | 15/11/2024 | Yes | No |
| Results article | 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 | 01/12/2021 | 15/11/2024 | Yes | No |
| Results article | Decrements in health‐related quality of life associated with adverse events in people with diabetes | 20/12/2021 | 15/11/2024 | Yes | No |
| Results article | Effects of aspirin on dementia and cognitive function in diabetic patients: the ASCEND trial | 01/06/2022 | 15/11/2024 | Yes | No |
| Results article | Hospital costs associated with adverse events in people with diabetes in the UK | 29/06/2022 | 15/11/2024 | Yes | No |
| Results article | Thromboxane biosynthesis and future events in diabetes: the ASCEND trial | 14/04/2024 | 15/11/2024 | Yes | No |
Additional files
- ISRCTN60635500_PIS_V8p4_12Oct2010.pdf
- Uploaded 07/05/2019
- ISRCTN60635500_EndOfStudyPIS_V1p0_16Nov2016.pdf
- Uploaded 07/05/2019
Editorial Notes
15/11/2024: The following changes were made to the trial record:
1. The IRAS number was added.
2. The primary outcome measure was changed.
3. The secondary outcome measures were changed.
4. The plain English summary was added.
5. The publication and dissemination plan was changed.
6. The contact email was changed.
7. The funders Bayer Schering Pharma AG (UK) and Solvay Pharmaceuticals GmbH (Germany) were removed.
8. Publication references added.
06/11/2024: Publication reference added.
25/09/2023: Publication reference added.
05/06/2023: Publication reference added.
06/03/2023: Publication reference added.
09/05/2019: The following changes were made to the trial record:
1. Publication and dissemination plan and IPD sharing statement added.
2. The overall trial end date was changed from 31/12/2017 to 31/07/2037.
07/05/2019: The following changes were made to the trial record:
1. The primary and secondary outcome measures were updated.
2. Added link to basic results (scientific).
3. Publication references added.
4. The total final enrolment number was added.
5. The participant information sheets have been uploaded.
01/02/2019: Publication reference added.
15/06/2016: Publication reference added.
11/02/2009: this record was updated to include amended trial dates. The initial trial dates at the time of registration were:
Initial overall trial start date: 01/03/2005
Initial overall trial end date: 01/03/2011
