Condition category
Circulatory System
Date applied
05/07/2012
Date assigned
05/07/2012
Last edited
06/05/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Atherosclerotic carotid stenosis is a narrowing of the carotid artery in the neck by fatty deposits. It is an important cause of stroke, and hence disability and premature death. Previous studies have shown that an operation to remove the narrowing, known as carotid endarterectomy (CEA), is more effective than treatment with tablets to prevent stroke. In some patients a treatment called stenting may be as effective as surgery. Stenting involves a wire mesh tube being inserted via an artery in the groin and opened up across the narrowing in the neck. However, drug treatment has improved since the original studies of surgery. We think medical treatment is now so effective that the benefits of removing the narrowing may not justify the risk of surgery or stenting in patients with a lower risk of stroke, such as those who have had no symptoms for some months or never had symptoms from the narrowing. The aim of this study is to determine whether these patients should be managed by drug treatment alone or should still be referred for surgery or stenting.

Who can participate?
Patients over 18 years of age with atherosclerotic carotid stenosis and at a lower risk of stroke.

What does the study involve?
Participants have their medication adjusted to reach the recommended levels for cholesterol and blood pressure, and receive advice about healthy lifestyle. Half of the patients are randomly allocated to have surgery or stenting as soon as possible, and the other half continue on medical treatment alone until such time, if ever, that revascularisation surgery becomes clearly indicated. Participants are seen regularly for several years to check their cholesterol and blood pressure remain on target and to record any surgical complications and the occurrence of strokes or heart attacks.

What are the possible benefits and risks of participating?
The results will be used to help patients and doctors to choose which treatment plan is the safest and most effective. Both surgical endarterectomy and stenting carry a risk of causing a stroke at the time of the treatment. Previous studies showed a risk of stroke or death at the time of surgery or stenting of between 3 and 6 patients in every 100 patients. Treatment is not always successful and the carotid stenosis may recur and require further treatment or the artery may become blocked. A proportion of people treated with optimized medical treatment will also suffer stroke at some time during follow-up despite treatment. Stroke caused by surgery, stenting or occurring during OMT may recover, cause permanent disablement or be fatal. Surgery also has a risk of causing a heart attack. About one in ten patients has cranial nerve palsy (temporary tongue or facial weakness). A haematoma (a solid swelling of clotted blood) may form at the site of incision, which may require removal. Angiography and stenting may also result in bruising or haematoma at the site of injection (usually in the groin) and can cause temporary discomfort or pain in the neck. There is a small risk of allergic reactions to the dye. The drugs used as part of OMT may cause adverse reactions or allergic reactions. The medical treatment that patients in both arms will receive will be carefully monitored and optimised with targets for control of blood pressure and lipid levels and advice on lifestyle. In the revascularisation group the surgeons and interventionists providing this treatment will have to show acceptable complication levels laid down in the protocol before their centre can be enrolled to randomise patients into the study. We have designed the protocol in such a way as to minimise risks to patients in both arms of the study and all patients should benefit from the optimisation and monitoring of their medical treatment.

Where is the study run from?
The National Hospital for Neurology and Neurosurgery (UK)

When is the study starting and how long is it expected to run for?
March 2012 to March 2022

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Mr Roland Featherstone
r.featherstone@ion.ucl.ac.uk

Trial website

http://www.ecst-2.com/

Contact information

Type

Scientific

Primary contact

Mr Roland Featherstone

ORCID ID

Contact details

The National Hospital for Neurology and Neurosurgery
Queen Square
London
WC1N 3BG
United Kingdom
-
r.featherstone@ion.ucl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

11034

Study information

Scientific title

European Carotid Surgery Trial 2 (ECST-2): a randomised controlled trial

Acronym

ECST 2

Study hypothesis

Narrowing of the carotid artery in the neck by fatty deposits is an important cause of stroke, and hence disability and premature death. Previous trials have shown that an operation to remove the narrowing, known as carotid endarterectomy (CEA), is more effective than treatment with tablets to prevent stroke. In some patients a treatment called stenting where a wire mesh tube is inserted via an artery in the groin and opened up across the narrowing in the neck may be as effective as surgery. However, drug therapy has improved since the original trials of surgery. We think medical therapy is now so effective that the benefits of removing the narrowing may not justify the risk of surgery or stenting in patients with a lower risk of stroke e.g. those who have had no symptoms for some months from the narrowing or never had symptoms. We propose a clinical trial to determine whether these patients should be managed by drug therapy alone or should still be referred for surgery or stenting.

More details can be found at http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=11034

Ethics approval

National Research Ethics Service Committee – East of England, Cambridge Central, 19/10/2011, ref: 11/EE/0347

Study design

Randomised controlled interventional trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Stroke

Intervention

Immediate endartorectomy and optimised medical therapy.

All patients will have their medication adjusted to reach recommended levels for cholesterol and blood pressure, and receive advice about healthy lifestyle. Half the patients will be randomly allocated to have surgery or stenting as soon as possible, the other half will continue on medical treatment alone until such time, if ever, that revascularisation becomes clearly indicated. Patients will be seen regularly for several years to check their cholesterol and blood pressure remain on target and to record surgical complications and the occurrence of strokes or heart attacks. An interim safety analysis will be performed using MRI follow up to assess rates of new cerebral infarction and haemorrhage.

Intervention type

Mixed

Phase

Drug names

Primary outcome measures

Any stroke at any time + non-stroke death within 30 days of endartorectomy

Secondary outcome measures

Added 06/05/2016:
The long-term rates of the following outcomes:
1. Ipsilateral stroke, confirmed/probable TIA, MI or any hospitalisation for vascular disease during follow up
2. Disabling stroke during follow up
3. New cerebral infarction or parenchymal haemorrhage on follow up MRI
4. Increase in white-matter changes on follow up MRI
5. Revascularisation during follow-up
6. Stenosis progression (defined as recurrent stenosis of the randomised artery after revascularisation, or progression in severity of stenosis in a non-revascularised artery)
7. The combination of stenosis progression or revascularisation during follow-up
8. Functional status as assessed by comparison of modified Rankin scale scores
9. The cost-effectiveness of carotid endarterectomy with OMT compared to OMT alone
10. Cognitive impairment or dementia during follow up reported by the investigator and measured by the Montreal Cognitive Assessment (MoCA)
11. Decline in functional status as assessed by an increase in the modified Rankin score (mRS)
12. Health-related quality of life and economic costs
Secondary analysis will also examine the risk factors for stroke, cognitive impairment and the other main outcome events during long term follow up (including the risks related to age, sex, symptoms, baseline brain imaging, centre and technique). In centres performing the relevant additional investigations, secondary analyses will examine the relationship between the main outcome events and baseline measures of plaque instability as determined by MR plaque imaging.

Overall trial start date

23/03/2012

Overall trial end date

31/03/2022

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients over 18 years of age with atherosclerotic carotid stenosis equivalent to at least 50% measured using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method
2. Patient is medically and neurologically stable and suitable for CEA or carotid artery stenting (CAS)
3. Patients with a carotid artery risk (CAR) score indicating a 5-year ipsilateral stroke risk of <20%. This may include patients with asymptomatic stenosis or symptomatic stenosis associated with features (e.g. delayed presentation) indicating intermediate or lower risk, confirmed by CAR Score <20%
4. Clinicians are uncertain about which treatment modality is best for the individual patient
5. Patient or appropriate representative is able and willing to give informed consent
6. Male and female participants

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 200

Participant exclusion criteria

1. Patients (or their representatives) unwilling to have either treatment modality
2. Patients unwilling or unable to participate in follow up for whatever reason
3. Patients with a Rankin score greater than 3 for any reason. Such patients may be eligible for inclusion at such time as they improve to a Rankin score of 3 or less
4. Patients who are medically or neurologically unstable or have progressing neurological signs. Such patients may be eligible for inclusion at such time as they become stable
5. Patients in whom it is planned to carry out coronary artery bypass grafting or other major surgery within one month of carotid stenting or endarterectomy
6. Patients with a CAR Score >20% or other reason for believing the patient would get clear benefit from CEA or CAS
7. Patients not suitable for either surgery or stenting due to anatomical factors
8. Carotid stenosis caused by nonatherosclerotic disease e.g. dissection, fibromuscular disease or neck radiotherapy
9. Previous CEA or stenting in the randomised artery
10. Patients who are known to be pregnant
11. Patients who have a life expectancy of less than two years due to a preexisting condition e.g. cancer
12. Patients intolerant or allergic to all of the medications available for optimised modern medical therapy
13. Patients in clinical trials of medicinal products (CTIMPS) or who have been in a CTIMP within the last 4 months will not be enrolled
14. Patients in other trials (both stroke related and non stroke related) may be enrolled where this would not conflict with the treatments used in ECST2 or place undue additional burdens on the patient

Recruitment start date

23/03/2012

Recruitment end date

31/03/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The National Hospital for Neurology and Neurosurgery
London
WC1N 3BG
United Kingdom

Trial participating centre

University College London Hospital
NW1 2BU
United Kingdom

Trial participating centre

Sheffield Teaching Hospitals
S10 2JF
United Kingdom

Trial participating centre

Cumberland Infirmary
CA2 7HY
United Kingdom

Trial participating centre

Nottingham University Hospitals
NG5 1PB
United Kingdom

Trial participating centre

Universitätsklinikum Magdeburg
Otto-von-Guericke-Universität
-
Germany

Trial participating centre

Leeds General Infirmary
LS1 3EX
United Kingdom

Trial participating centre

Calderdale & Huddersfield NHS Foundation Trust
HD3 3EA
United Kingdom

Trial participating centre

Frimley Park Hospital
GU16 7UJ
United Kingdom

Trial participating centre

Academic Medical Centre, Amsterdam and Flevoziekenhuis, Almere
-
Netherlands

Trial participating centre

East Kent University Hospital NHS Foundation Trust,
CT1 3NG
United Kingdom

Trial participating centre

Royal Devon and Exeter Hospital
EX2 5DW
United Kingdom

Trial participating centre

Albert Schweitzer Hospital Dordrecht
-
Netherlands

Trial participating centre

University Hospitals Coventry and Warwickshire
CV2 2DX
United Kingdom

Trial participating centre

St George's Healthcare NHS Trust
SW17 0QT
United Kingdom

Trial participating centre

Manchester Royal Infirmary
M13 9WL
United Kingdom

Trial participating centre

NHS Ayrshire & Arran
KA27 8AJ
United Kingdom

Trial participating centre

Stroke Centre, University Hospital Basel
-
Switzerland

Trial participating centre

Bradford Teaching Hospitals NHS Trust
BD9 6RJ
United Kingdom

Trial participating centre

University Hospital North Durham
DH1 5TW
United Kingdom

Trial participating centre

University Hospital South Manchester
M23 9LT
United Kingdom

Trial participating centre

Erasmus Medical Centre Rotterdam
-
Netherlands

Sponsor information

Organisation

University College London (UK)

Sponsor details

Institute of Neurology
Queen Square
London
WC1N 3BG
United Kingdom

Sponsor type

University/education

Website

http://www.ucl.ac.uk/

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

11/02/2016: Plain English summary added.