Comparing endovascular (keyhole) surgery with open surgery for the treatment of acute limb ischaemia (ALI) of the lower limb
| ISRCTN | ISRCTN15236323 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15236323 |
| Integrated Research Application System (IRAS) | 347905 |
| Central Portfolio Management System (CPMS) | 64354 |
| National Institute for Health and Care Research (NIHR) | 167680 |
| Sponsor | Newcastle upon Tyne Hospitals NHS Foundation Trust |
| Funder | National Institute for Health and Care Research |
- Submission date
- 25/08/2026
- Registration date
- 26/08/2026
- Last edited
- 26/08/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Acute limb ischaemia (ALI) is a common emergency condition. ALI occurs when the arteries supplying blood to the legs suddenly become blocked by a blood clot. Without blood flow to the legs, nerves, muscles and skin can die within hours, leading to amputation or death. Approximately one in ten people treated for ALI in the NHS die in hospital within a few days, and around four in ten die within one year. ALI is one of the most common causes of amputation in the NHS.
In people with ALI, treatment involves an emergency procedure to unblock the affected artery. This can be performed using either open surgery or keyhole (endovascular) surgery. Open surgery requires a skin incision to open the affected artery and remove or bypass the clot. Keyhole surgery can be performed under local anaesthetic and requires only small needle punctures. It is unclear which treatment approach is more effective at preventing amputations and deaths, or which provides better value for money for the NHS. This study aims to address this uncertainty and determine which treatment option is more effective.
The aim of this research is to determine whether open surgery is more effective than keyhole (endovascular) surgery for treating people with ALI of the leg in terms of preventing death, amputation and hospital readmissions over six months.
Who can participate?
Adults aged 18 years and over with ALI of the lower limb can participate.
What does the study involve?
Participants are randomly allocated to receive either open surgery or keyhole (endovascular) surgery to treat their ALI. Random allocation means that neither the participant nor their clinical team chooses which surgical treatment is received. Participants are allocated to one of the following groups:
-Open surgery for the treatment of ALI
-Keyhole (endovascular) surgery for the treatment of ALI
Participants are followed up for six months. Most study data are collected from medical records. Following surgery, participants attend two clinic appointments, one at 30 days and one at six months, for vascular assessments that form part of routine NHS care after these procedures. These visits usually last approximately 30 minutes. Participants are also asked to complete questionnaires at 30 days and six months covering quality of life, symptoms and any additional treatments received.
What are the possible benefits and risks of participating?
Participants may not receive a direct personal benefit from taking part. However, participation contributes to improving the treatment of future patients with ALI. The study findings may help inform the planning and delivery of effective NHS services in the future.
Participation helps evaluate open and keyhole surgery for ALI and is not expected to involve additional risk. All procedures and techniques used in the study are already established NHS treatments for ALI. Regardless of treatment allocation, surgery is performed by appropriately trained and competent clinicians.
Where is the study run from?
The Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
September 2026 to March 2029
Who is funding the study?
The study is funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) Programme (UK).
Who is the main contact?
Dr Lynda Constable (establish@abdn.ac.uk)
Contact information
Scientific, Public
Aberdeen Centre for Evaluation (ACE), 3rd Floor Health Sciences Building, Foresterhill
Aberdeen
AB25 2ZD
United Kingdom
 ORCID ID |
0000-0001-9646-3904 |
|---|---|
| l.constable@abdn.ac.uk |
Principal investigator
Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Level 4 - Freeman Hospital, Freeman Road
Newcastle-upon-Tyne
NE7 7DN
United Kingdom
| ORCID ID |
0000-0002-6036-5760 |
|---|---|
| sandip.nandhra@newcastle.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Open (masking not used) |
| Control | Active |
| Assignment | Single |
| Purpose | Treatment |
| Scientific title | Endovascular strategy versus Surgical strategy for the Treatment of Acute Limb Ischaemia of the lower limb |
| Study acronym | ESTABLISH |
| Study objectives | Primary objective: To compare open surgical revascularisation strategy to endovascular revascularisation strategy in terms of amputation-free survival at 6-months Secondary objectives: To compare open surgical revascularisation strategy to endovascular revascularisation strategy in terms of mortality, lower limb amputation, re-interventions, duration of hospital stay and hospital re-admissions, cardiovascular events, cardiovascular medications and quality-of-life up to 6 months after randomisation. Additionally, to estimate the relative cost-effectiveness to the NHS and personal social services (PSS) of the two approaches |
| Ethics approval(s) |
Approved 29/07/2026, West of Scotland REC 5 (West of Scotland Research Ethics Service, Level 2, Administration Building, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 0XH, United Kingdom; +44 141 314 0213; ggc.wosrec5@nhs.scot), ref: 26/WS/0110 |
| Health condition(s) or problem(s) studied | Acute limb ischaemia of the lower limb |
| Intervention | Randomisation will occur after all eligibility criteria are confirmed, and after verbal or fully informed consent has been obtained. Participants will be randomised in a 1:1 ratio to either open surgical strategy or endovascular strategy using a remote central, computer-generated minimisation algorithm hosted by CHaRT. The minimisation variables are age (<50, 50-69, 70+ years), sex (male, female), centre, clinical frailty score (≤3 not frail, >3 frail), and disease condition (unilateral, bilateral). Given the urgent nature of ALI, we anticipate that the intervention will take place within 48 hours of randomisation in most cases, however we are not stipulating the timing of intervention from randomisation – we expect procedures to take place as promptly as clinically appropriate, as decided by the treating clinicians and local practice. Participants will be asked to complete a short baseline questionnaire prior to knowing their randomised allocation. Due to the nature of the interventions, there is no blinding of site staff or participants. The intervention (open or endovascular strategy) to treat their ALI will be undertaken, as part of usual clinical practice. Participants will have clinical vascular assessments as per NHS standard of care at 30 days and 6 months after randomisation (this usually lasts around 30 minutes). Participant reported outcome measures (EQ-5D-5L and VascuQol-6) will be collected at baseline, 30 days and 6 months after randomisation. |
| Intervention type | Other |
| Primary outcome measure(s) |
Death and/or major amputation (defined as time to death and/or ipsilateral major (above ankle) lower limb amputation) measured using medical records/patient report at up to six months post randomisation (30 days and 6 months) |
| Key secondary outcome measure(s) |
1. Major lower limb amputation measured using medical records up to six months post randomisation (30 days and 6 months) |
| Completion date | 31/03/2029 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 120 Years |
| Sex | All |
| Target sample size at registration | 470 |
| Key inclusion criteria | 1. Adults aged 18 years and over 2. ALI of the lower limb (all-comers i.e. embolic and thrombosis in situ and bilateral presentation (with allocation to the treatment strategy at the participant level, see Protocol section 4.4) suitable for open or endovascular intervention, and requiring revascularisation as deemed appropriate by the treating clinicians 3. Able and willing to give informed consent to participate and to participate in study procedures |
| Key exclusion criteria | 1. Not suitable for open repair or endovascular surgery (technical or clinical rationale) 2. Non-salvageable limb 3. Current pregnancy or lactation 4. Allergy to contrast agent(s) 5. People who do not have the capacity to consent for themselves |
| Date of first enrolment | 01/09/2026 |
| Date of final enrolment | 30/06/2028 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
Study participating centres
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
England
St Marys Hospital
South Wharf Road
London
W2 1BL
England
Wilberforce Court
Alfred Gelder Street
Hull
HU1 1UY
England
Beckett Street
Leeds
LS9 7TF
England
Frimley
Camberley
GU16 7UJ
England
Wigginton Road
York
YO31 8HE
England
2-4 Waterloo Place
Edinburgh
EH1 3EG
Scotland
Oxford Road
Manchester
M13 9WL
England
Infirmary Square
Leicester
LE1 5WW
England
Lydeard House
Musgrove Park Hospital
Taunton
TA1 5DA
England
Pond Street
London
NW3 2QG
England
Watford Road
Harrow
HA1 3UJ
England
Anlaby Road
Hull
HU3 2JZ
England
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
England
Sandford Road
Cheltenham
GL53 7AN
England
Armthorpe Road
Doncaster
DN2 5LT
England
Westminster Bridge Road
London
SE1 7EH
England
Northampton
NN1 5BD
England
Dundee
DD1 9SY
Scotland
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
25/08/2026: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
