Long-term follow-up of participants in the electronic health records from the SEARCH Study
| ISRCTN | ISRCTN14416153 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14416153 |
| IRAS number | 266042 |
| Secondary identifying numbers | IRAS 266042, PID14408-SP001-AC001 |
- Submission date
- 16/08/2022
- Registration date
- 25/08/2022
- Last edited
- 13/12/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Other
Plain English summary of protocol
Background and study aims
The SEARCH study (https://doi.org/10.1186/ISRCTN74348595) was a randomised, multi-centre, factorial trial of LDL (low-density lipoprotein) cholesterol lowering, comparing higher versus standard dose simvastatin (a drug used to lower cholesterol for people diagnosed with high blood cholesterol), and homocysteine (an amino acid) lowering comparing folic acid and vitamin B12 supplementation versus placebo in 12,064 patients with an average age of 64 and with a history of heart attacks (myocardial infarction (MI)). It was run in 88 UK clinical centres for ten years. Participants in SEARCH were recruited to the trial between September 1998 and October 2001, with all final follow-up assessments completed by June 2008. Results were presented at the American Heart Association meeting in 2008 and published in the Lancet & JAMA in 2010.
SEARCH found that:
1. The allocation of simvastatin 80 mg daily versus 20 mg daily reduced LDL-cholesterol by 0.35 mmol/L and reduced major vascular events (i.e. heart attacks, strokes or coronary or non-coronary revascularisation) by 6% (95% CI 12% to +1%). This reduction was in line with expectations and contributed to the Cholesterol Trialists’ Collaboration (CTT) meta-analysis that showed that more intensive LDL-cholesterol lowering produces additional benefits.
2. Supplementation with folic acid plus vitamin B12 significantly reduced homocysteine levels and is safe, but did not reduce the risk of major vascular events or cancer
3. Simvastatin 80 mg daily was associated with an increased risk of myopathy (muscle symptoms with raised blood creatine kinase) with 53 versus 2 cases respectively among those allocated 80 mg versus 20 mg simvastatin daily
Participants were recruited into the main trial using informed patient consent as a legal basis to process data. However, the researchers now have section 251 support (from the Confidentiality Advisory Group (Ref: 19/CAG/0167)) in place to carry out long-term research on this cohort. The data controller has approval from the West of Scotland Research Ethics Service (Ref: 19/WS/0115) to follow up on the cohort, with continued data linkage to allow for future analyses.
The purpose of this SEARCH long-term follow-up study is to determine factors that contribute to the health of trial participants in the longer term.
Who can participate?
The cohort is the original SEARCH participants recruited in UK hospitals between 1998 and 2001. No further participants will be added to this trial.
What does the study involve?
This is a long-term follow-up study. That means that we will be using data previously collected from participants during the main trial, and also collecting data about them from electronic health records (e.g. from NHS England, and equivalent bodies in Scotland and Wales). Participants will not be contacted directly.
What are the possible benefits and risks of participating?
No interventions are taking place for this long-term follow-up study so there are no direct risks or benefits to participants.
Where is the study run from?
University of Oxford and is managed by researchers at the Nuffield Department of Population Health (United Kingdom)
When is the study starting and how long is it expected to run for?
July 2019 to December 2035
Who is funding the study?
University of Oxford (UK)
Who is the main contact?
Prof. Jane Armitage (Chief Investigator), search@ndph.ox.ac.uk
Contact information
Scientific
Oxford Population Health
Nuffield Department of Population Health
University of Oxford
Old Road Campus
Oxford
OX3 7LF
United Kingdom
 ORCID ID |
0000-0002-4816-8991 |
|---|---|
| Phone | +44 (0)1865 743743 |
| william.whiteley@ed.ac.uk |
Public
Oxford Population Health
Nuffield Department of Population Health
University of Oxford
Old Road Campus
Oxford
OX3 7LF
United Kingdom
| ORCID ID |
0000-0003-3195-2613 |
|---|---|
| Phone | +44 (0)1865 743743 |
| michelle.nunn@ndph.ox.ac.uk |
Study information
| Study design | Extended follow-up study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Medical and other records |
| Study type | Other, Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | SEARCH trial legacy study: Long-term follow-up of participants using electronic health records |
| Study objectives | To determine the factors that contribute to the health of UK participants of the original SEARCH trial (ISRCTN74348595) over many years, using electronic health records |
| Ethics approval(s) | Approved 30/08/2019, West of Scotland REC 3 (Research Ethics, Clinical Research & Development, Dykebar Hospital, Grahamston Road, Paisley, PA2 7DE, United Kingdom; +44 (0)141 314 0211; WoSERC3@ggc.scot.nhs.uk), ref: 19/WS/0115 |
| Health condition(s) or problem(s) studied | Cardiovascular disease, dementia, cancer |
| Intervention | Record-level electronic health data will be requested from NHS England and equivalent registries in Scotland & Wales. These records will be used to follow up on the original SEARCH cohort for an extended period after the end of the main trial in 2008. No direct intervention will take place, and participants will not be contacted directly. |
| Intervention type | Other |
| Primary outcome measure | The first planned analyses will be based on at least 15 years’ follow-up from trial initiation with further analyses planned at approximately 5 yearly intervals based on ongoing linkage to NHS records. Appropriate analysis methods will be used to compare the risk ratios for first occurrence post-randomisation of each outcome of interest (dementia, stroke, all major cardiovascular disorders, other vascular disease complications, myopathies, heart failure, renal impairment, other health and care outcomes and death) between both allocated treatment groups. |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 16/07/2019 |
| Completion date | 31/12/2035 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 75 Years |
| Sex | Both |
| Target number of participants | 12064 |
| Key inclusion criteria | Participants were part of the original SEARCH cohort (randomised between 1998 and 2001). They were between 18 and 75 years old when invited to participate. Participants had to fulfil all of the following criteria: 1. History of prior myocardial infarction 2. Current use of a statin or clear indication for statin therapy 3. No clear indication for folic acid 4. No clear contraindications to the study treatments 5. No other medical problem For inclusion into the legacy cohort, participants had to be residents of the UK |
| Key exclusion criteria | 1. Participants who have opted out of having their data provided by NHS England 2. Participants who have read the privacy notice and have decided that they do not want their data used in this study |
| Date of first enrolment | 15/06/2022 |
| Date of final enrolment | 31/12/2035 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Oxford
Richard Doll Building
Old Road Campus
Oxford
OX3 7LF
United Kingdom
Sponsor information
University/education
Research Governance, Ethics & Assurance
University of Oxford
1st floor, Boundary Brook House
Churchill Drive
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 (0)1865 289885 |
|---|---|
| rgea.sponsor@admin.ox.ac.uk | |
| Website | https://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
University/education
Government organisation / Universities (academic only)
- Alternative name(s)
- University in Oxford, Oxford University, 牛津大学, Universitas Oxoniensis
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/06/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | Procedures for accessing the data for this study are available at https://www.ndph.ox.ac.uk/data-access |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1 | 15/05/2019 | 17/08/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
13/12/2024: The following changes have been made:
1. The intention to publish date was changed from 31/12/2024 to 30/06/2026.
2. The Sponsor was updated.
05/12/2023: The following changes have been made:
1. The intention to publish date changed from 31/12/2023 to 31/12/2024.
2. ORCID ID added.
3. Study setting medical and other records was added and other was removed.
4. Study type treatment added.
5. NHS Digital was updated to NHS England throughout.
31/08/2022: This study is a long-term follow-up of participants in the SEARCH study (ISRCTN74348595).
17/08/2022: Trial's existence confirmed by the West of Scotland REC 3 Research Ethics Committee.
