Plain English Summary
Background and study aims
One in every 1000-2000 people in the UK will be diagnosed with advanced cases of Severe Limb Ischemia (SLI) yearly. As a result of a combination of smoking, diabetes, high blood pressure, high cholesterol levels, kidney failure and the ageing process, some people develop hardening of the arteries in their legs. In SLI, even minor injuries to the foot can fail to heal, resulting in the development of ulceration, even gangrene. Unless the blood supply to the leg and foot is improved, many people affected by SLI will lose their limb and/or die within 12 months. As well as causing great suffering, SLI places a large financial burden upon health and social care services. The two treatments currently available for SLI are vein bypass (VB) and best endovascular treatment (BET). In VB a vein is used to bypass the blockage. BET involves opening up the diseased arteries with balloons and sometimes the use of little metal tubes called stents. Both treatments have pros and cons and there is debate and uncertainty as to which is preferable, when, in which arteries, and in which patients.
Who can participate?
This study aims to recruit 600 adult patients with SLI from the participating hospitals.
What does the study involve?
Patients will be randomly allocated to receive either vein bypass surgery or the best endovascular treatment. Patients will be followed up clinically for 3 years and asked to complete questionnaires at 10 time points over this time. The 10 time points have been selected to occur at the same time as the patient would normally have a clinical appointment - there are no additional appointments.
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
The study is run from about 40 hospitals within the British Isles.
When is the study starting and how long is it expected to run for?
The study runs from May 2014 until October 2019. Recruitment starts in May 2014 and continues for 3 years.
Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK).
Who is the main contact?
Clinical Lead: Professor Andrew Bradbury, email@example.com
Administrative contact: Mr Hugh Jarrett, firstname.lastname@example.org
Multicentre randomised controlled trial to compare the clinical and cost-effectiveness of a vein bypass first with an endovascular first revascularisation strategy for severe limb ischaemia (SLI) due to infrageniculate arterial disease
The clinical and cost effectiveness of a bypass surgery first strategy compared with an angioplasty first strategy is superior for treating people with critical limb ischaemia caused by disease of the infra-popliteal arteries.
More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/123545
NRES West Midlands (Coventry & Warwick); 03/03/2014; ref: 14/WM/0057
Randomised multicentre pragmatic two-arm open trial incorporating an internal pilot phase and within-trial health economic analysis
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Severe ischaemia of the lower limb due to infrageniculate arterial disease
The interventions are either vein bypass surgery or best endovascular treatment. Best endovascular treatment will involve balloon angioplasty and possibly the use of stents. Randomisation will be on a 1:1 basis, and patients will be followed up for 3 years with clinic visits at 1, 3, 6, 9, 12, 18, 24, 30, and 36 months post randomisation. These clinic visits coincide with the pattern of visits for standard practice.
Primary outcome measures
Amputation Free Survival (AFS), defined as the time to major limb (above the ankle) amputation of the index (trial) limb or death from any cause.
Secondary outcome measures
1. Overall Survival (OS)
2. In-hospital and 30-day morbidity and mortality
3. Major Adverse Limb Event, defined as amputation (transtibial or above) or any major vascular re-intervention (thrombectomy, thrombolysis, balloon angioplasty, stenting, or surgery)
4. Major cardiovascular events (SLI and amputation affecting the contralateral limb, acute coronary syndrome, stroke)
5. Relief of ischaemic pain [visual analogue scale (VAS), medication usage]
6. Psychological morbidity [Hospital Anxiety and Depression Scale (HADS)]
7. Quality of life (QoL) using generic [EQ-5D-5L, SF-12, ICEpop CAPability measure for Older people (ICECAP-O)] and disease-specific (VascuQoL) tools
8. Re- and cross-over intervention rates
9. Healing of tissue loss (ulcers, gangrene) as assessed by the PEDIS and the WiFi scoring and classification systems
10. Extent and healing of minor (toe and forefoot) amputations (also using PEDIS and WiFi)
11. Haemodynamic changes; absolute ankle and toe pressures, ankle brachial pressure index (ABPI), toe brachial pressure index (TBPI)
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Have Severe Limb Ischaemia (SLI) due to infra-popliteal (IP), with or without femoro-popliteal (FP) disease
2. Be judged by the responsible clinicians (consultant vascular surgeon (VS), interventional radiologist (IR), diabetologists) working as part of a multi-disciplinary team (MDT) to require early infra-popliteal (IP), with or without femoro-popliteal (FP), revascularisation in addition to Best Medical Treatment (BMT), foot and wound care
3. Have Aorto-Iliac (AI) inflow adequate to support Vein Bypass (VB) and Best Endovascular Treatment (BET) (if not, then patients can be randomised after a successful AI procedure which can be either surgical or endovascular)
4. Be judged suitable for both Vein Bypass and Best Endovascular Treatment following diagnostic imaging and a formal (documented) discussion by consultant vascular surgeon and interventional radiologist in a properly constituted multi-disciplinary team meeting
Target number of participants
Participant exclusion criteria
Patients will be excluded if they:
1. Have an anticipated life expectancy <6 months
2. Are unable to provide consent due to incapacity (as defined by Mental Capacity Act 2005 or Adults with Incapacity [Scotland] Act 2000)
3. Are a non-English speaker where translation facilities are insufficient to guarantee informed consent
4. Are judged unsuitable for either of the two revascularisation strategies by the responsible consultant VS and IR
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Heart of England NHS Foundation Trust
University of Birmingham (UK)
Research Support Group
Aston Webb Building
+44 (0)121 415 8011
NIHR Health Technology Assessment Programme - HTA (UK); ref. 12/35/45
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26739146