Condition category
Circulatory System
Date applied
15/04/2005
Date assigned
12/09/2005
Last edited
05/05/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
About 85% of strokes are ischemic strokes, in which the blood flow to the brain is blocked by a blood clot (ischaemia). As we age, deposits of a fatty substance called plaque can build-up in the main arteries in the neck (carotid arteries). Over time, this plaque can greatly reduce the diameter of the arteries (stenosis), even blocking them all together (occlusion). If the artery is particularly stenosed (with a reduction in diameter of more than 50%) surgical treatment may be recommended to restore blood flow, reducing the risk of stroke. Traditionally, this is done using a procedure called a carotid endarterectomy, in which the blockage itself is removed through a surgical incision (cut). Carotid angioplasty and stenting is an alternative, less invasive procedure which is becoming more popular. This is considered to be a good alternative to open surgery as it is less risky and so can be used for people who are too unwell for an endarterectomy. It is done by placing a thin tube (catheter) into a large artery (usually in the leg) and guiding it to the stenosed carotid artery. A small balloon is then inflated to “flatten” the blockage against the artery wall and a stent (small mesh tube) is placed inside in order to keep the artery open. The aim of this study is to compare the risks and benefits of these two procedures in patients with carotid stenosis.

Who can participate?
Adults over 40 years of age with a narrowing of their carotid arteries of at least 50%.

What does the study involve?
Participants are randomly allocated to one of two groups. Participants in the first group receive a carotid endarterectomy procedure. This involves a small cut being made in the narrowed section of the affected artery (accessed through a cut in the neck), so that the plaque can be removed by the surgeon before it is stitched closed again. Participants in the second group receive carotid artery stenting. This involves the surgeon inserting a catheter (thin tube) into the main artery of the leg (femoral artery) and guiding it up to the narrowed carotid artery with help from a special dye visible on a type of x-ray (angiogram). A guide wire inside the catheter is then used to manoeuvre the stent and balloon into the carotid artery. The balloon is placed inside the stent and inflated in order to open the stent and push it into place against the artery wall. The balloon is then deflated and removed, leaving the stent in place. Participants in both groups are then followed up in order to record the number of people who suffer from a stroke or die.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
University College London (UK)

When is the study starting and how long is it expected to run for?
May 2000 to December 2010

Who is funding the study?
Medical Research Council (UK)

Who is the main contact?
Professor Martin Brown
m.brown@ion.ucl.ac.uk

Trial website

http://www.cavatas.com

Contact information

Type

Scientific

Primary contact

Prof Martin M Brown

ORCID ID

Contact details

Professor of Stroke Medicine
Institute of Neurology
University College London
Box 6
National Hospital for Neurology & Neurosurgery
Queen Square
London
WC1N 3BG
United Kingdom
+44 (0)20 7829 8753
m.brown@ion.ucl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

A randomised comparison of the risks, benefits and cost effectiveness of primary carotid stenting with cartotid endarterectomy: International Carotid Stenting Study

Acronym

ICSS

Study hypothesis

Added as of 07/02/2007:
To compare the risks, benefits and cost effectiveness of a treatment policy of referral for carotid stenting compared with referral for carotid surgery, in patients with symtomatic carotid stenosis.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Patient information sheet available at: http://www.ion.ucl.ac.uk/cavatas_icss/downloads/Infosheet.pdf

Condition

Carotid stenosis/stroke

Intervention

Patients will be randomised in equal proportions to be treated by carotid endarterectomy or stenting.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

Added as of 07/02/2007:
1. Any stroke or death
2. MI Within 30 days of treatment

Secondary outcome measures

Added as of 07/02/2007:
1. Cranial nerve palsy within 30 days of treatment
2. Haematoma caused by treatment requiring surgery
3. Transfusion or prolonging hospital stay
4. Stenosis greater than 70% or occlusion during follow up
5. Further treatment of the randomised artery by interventional radiology techniques or surgery after the initial attempt
6. Quality of life
7. Health status
8. Health Service costs

Overall trial start date

01/05/2000

Overall trial end date

31/12/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Symptomatic, extracranial, internal or bifurcation, atheromatous carotid artery stenosis that is suitable for both stenting and surgery and is deemed by the randomising clinician to require treatment
2. The severity of the stenosis of the randomised artery should be at least 50% (as measured by the North American Symptomatic Carotid Endarterectomy Trial [NASCET] method or non-invasive equivalent)
3. Symptoms must have occurred in the 12 months before randomisation. It is recommended that the time between symptoms and randomisation should be less than 6 months, but patients with symptoms occurring between 6 and 12 months may be included if the randomising physician considers treatment indicated
4. The patient must be clinically stable following their most recent symptoms attributable to the stenotic vessel
5. Patients must be willing to have either treatment, be able to provide informed consent, and be willing to participate in follow up
6. Patients must be able to undergo their allocated treatment as soon as possible after randomisation
7. Any age greater than 40 may be included. There is no upper age limit.
8. Patients should only be randomised if the investigator is uncertain which of the two treatments is best for that patient at that time

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

36

Participant exclusion criteria

1. Patients refusing either treatment
2. Patients unable or unwilling to give informed consent
3. Patients unwilling or unable to participate in follow up for whatever reason
4. Patients who have had a major stroke with no useful recovery of function within the territory of the treatable artery
5. Patients with a stenosis that is known to be unsuitable for stenting prior to randomisation because of one or more of:
5.1. Tortuous anatomy proximal or distal to the stenosis
5.2. Presence of visible thrombus
5.3. Proximal common carotid artery stenotic disease
5.4. Pseudoocclusion ('string sign')
6. Patients not suitable for surgery due to anatomical factors e.g. high stenosis, rigid neck
7. Patients in whom it is planned to carry out coronary artery bypass grafting or other major surgery within 1 month of carotid stenting or endarterectomy
8. Carotid stenosis caused by non-atherosclerotic disease e.g. dissection, fibromuscular disease or neck radiotherapy
9. Previous carotid endarterectomy or stenting in the randomised artery
10. Patients in who common carotid artery surgery is planned
11. Patients medically not fit for surgery
12. Patients who have a life expectancy of less than two years due to a pre-existing condition, e.g. cancer

Recruitment start date

01/05/2000

Recruitment end date

31/12/2010

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University College London
London
WC1N 3BG
United Kingdom

Sponsor information

Organisation

University College London (UK)

Sponsor details

Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

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

Publication summary

1. 2007 initial RCT results in http://www.ncbi.nlm.nih.gov/pubmed/17395869
2. 2007 computed tomographic measurement results in http://www.ncbi.nlm.nih.gov/pubmed/17848682
3. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20189239
4. 2010 sub-study results in http://www.ncbi.nlm.nih.gov/pubmed/20189458
5. 2011 cognition effect results in http://www.ncbi.nlm.nih.gov/pubmed/21880992
6. 2011 hypertension results in http://www.ncbi.nlm.nih.gov/pubmed/21998053
7. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/23238861
8. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23237679
9. 2013 blood flow velocity results in http://www.ncbi.nlm.nih.gov/pubmed/23578600
10. 2013 white-matter lesions results in http://www.ncbi.nlm.nih.gov/pubmed/23849948
11. 2013 flow velocities in the external carotid artery results in: http://www.ncbi.nlm.nih.gov/pubmed/23954165
12. 2013 predictors for acute and persisting periprocedural ischemic brain lesions results in: http://www.ncbi.nlm.nih.gov/pubmed/24368558
13. 2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24203845
14. 2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25344019
15. 2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/23834300
16. 2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25453443
17. 2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25677309
18. 2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26460291
19. 2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26979174
20. 2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26481656

Publication citations

  1. Initial RCT results

    Coward LJ, McCabe DJ, Ederle J, Featherstone RL, Clifton A, Brown MM, , Long-term outcome after angioplasty and stenting for symptomatic vertebral artery stenosis compared with medical treatment in the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomized trial., Stroke, 2007, 38, 5, 1526-1530, doi: 10.1161/STROKEAHA.106.471862.

  2. Computed tomographic measurement results

    Waaijer A, van Leeuwen MS, van Osch MJ, van der Worp BH, Moll FL, Lo RT, Mali WP, Prokop M, Changes in cerebral perfusion after revascularization of symptomatic carotid artery stenosis: CT measurement., Radiology, 2007, 245, 2, 541-548, doi: 10.1148/radiol.2451061493.

  3. Cognition effect results

    Altinbas A, van Zandvoort MJ, van den Berg E, Jongen LM, Algra A, Moll FL, Nederkoorn PJ, Mali WP, Bonati LH, Brown MM, Kappelle LJ, van der Worp HB, Cognition after carotid endarterectomy or stenting: a randomized comparison., Neurology, 2011, 77, 11, 1084-1090, doi: 10.1212/WNL.0b013e31822e55b9.

  4. Hypertension results

    Altinbas A, Algra A, Brown MM, Featherstone RL, Kappelle LJ, de Borst GJ, Mali WP, van der Worp HB, Effects of carotid endarterectomy or stenting on blood pressure in the International Carotid Stenting Study (ICSS)., Stroke, 2011, 42, 12, 3491-3496, doi: 10.1161/STROKEAHA.111.624478.

  5. Results

    Gensicke H, Zumbrunn T, Jongen LM, Nederkoorn PJ, Macdonald S, Gaines PA, Lyrer PA, Wetzel SG, van der Lugt A, Mali WP, Brown MM, van der Worp HB, Engelter ST, Bonati LH, , Characteristics of ischemic brain lesions after stenting or endarterectomy for symptomatic carotid artery stenosis: results from the international carotid stenting study-magnetic resonance imaging substudy., Stroke, 2013, 44, 1, 80-86, doi: 10.1161/STROKEAHA.112.673152.

  6. Results

    Rantner B, Goebel G, Bonati LH, Ringleb PA, Mas JL, Fraedrich G, , The risk of carotid artery stenting compared with carotid endarterectomy is greatest in patients treated within 7 days of symptoms., J. Vasc. Surg., 2013, 57, 3, 619-626.e2; discussion 625-6, doi: 10.1016/j.jvs.2012.08.107.

  7. Blood flow velocity results

    Reichmann BL, Hellings WE, van der Worp HB, Nederkoorn PJ, Algra A, Brown MM, Moll FL, Mali WP, de Borst GJ, Interprocedural comparison of changes in natural flow velocity patterns in the internal carotid artery following CAS or CEA., Eur J Vasc Endovasc Surg, 2013, 45, 6, 554-561, doi: 10.1016/j.ejvs.2013.02.013.

  8. Flow velocities in the external carotid artery results

    Reichmann BL, Hellings WE, van der Worp HB, Algra A, Brown MM, Mali WP, Moll FL, de Borst GJ, Flow velocities in the external carotid artery following carotid revascularization., Eur J Vasc Endovasc Surg, 2013, 46, 4, 411-417, doi: 10.1016/j.ejvs.2013.07.002.

  9. Predictors for acute and persisting periprocedural ischemic brain lesions results

    Rostamzadeh A, Zumbrunn T, Jongen LM, Nederkoorn PJ, Macdonald S, Lyrer PA, Kappelle LJ, Mali WP, Brown MM, van der Worp HB, Engelter ST, Bonati LH, , Predictors of acute and persisting ischemic brain lesions in patients randomized to carotid stenting or endarterectomy., Stroke, 2014, 45, 2, 591-594, doi: 10.1161/STROKEAHA.113.003605.

  10. Results

    Altinbas A, Algra A, Bonati LH, Brown MM, Kappelle LJ, de Borst GJ, Hendrikse J, van der Tweel I, van der Worp HB, , Periprocedural hemodynamic depression is associated with a higher number of new ischemic brain lesions after stenting in the International Carotid Stenting Study-MRI Substudy., Stroke, 2014, 45, 1, 146-151, doi: 10.1161/STROKEAHA.113.003397.

  11. Results

    Doig D, Turner EL, Dobson J, Featherstone RL, de Borst GJ, Brown MM, Richards T, , Incidence, Impact, and Predictors of Cranial Nerve Palsy and Haematoma Following Carotid Endarterectomy in the International Carotid Stenting Study., Eur J Vasc Endovasc Surg, 2014, doi: 10.1016/j.ejvs.2014.08.002.

  12. Results

    Altinbas A, Algra A, Brown MM, Featherstone RL, Kappelle LJ, de Borst GJ, Mali WP, van der Worp HB, , Effects of carotid endarterectomy or stenting on hemodynamic complications in the International Carotid Stenting Study: a randomized comparison., Int J Stroke, 2014, 9, 3, 284-290, doi: 10.1111/ijs.12089.

  13. , Ederle J, Dobson J, Featherstone RL, Bonati LH, van der Worp HB, de Borst GJ, Lo TH, Gaines P, Dorman PJ, Macdonald S, Lyrer PA, Hendriks JM, McCollum C, Nederkoorn PJ, Brown MM, Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial., Lancet, 2010, 375, 9719, 985-997, doi: 10.1016/S0140-6736(10)60239-5.

  14. Bonati LH, Jongen LM, Haller S, Flach HZ, Dobson J, Nederkoorn PJ, Macdonald S, Gaines PA, Waaijer A, Waajier A, Stierli P, Jäger HR, Lyrer PA, Kappelle LJ, Wetzel SG, van der Lugt A, Mali WP, Brown MM, van der Worp HB, Engelter ST, , New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS)., Lancet Neurol, 2010, 9, 4, 353-362, doi: 10.1016/S1474-4422(10)70057-0.

  15. Ederle J, Davagnanam I, van der Worp HB, Venables GS, Lyrer PA, Featherstone RL, Brown MM, Jäger HR, , Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial., Lancet Neurol, 2013, 12, 9, 866-872, doi: 10.1016/S1474-4422(13)70135-2.

  16. Results

    Bonati LH, Dobson J, Featherstone RL, Ederle J, van der Worp HB, de Borst GJ, Mali WP, Beard JD, Cleveland T, Engelter ST, Lyrer PA, Ford GA, Dorman PJ, Brown MM; International Carotid Stenting Study investigators, Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial, Lancet, 2015, 385, 9967, 529-538, doi: 10.1016/S0140-6736(14)61184-3.

  17. Results

    Gensicke H, van der Worp HB, Nederkoorn PJ, Macdonald S, Gaines PA, van der Lugt A, Mali WP, Lyrer PA, Peters N, Featherstone RL, de Borst GJ, Engelter ST, Brown MM, Bonati LH; ICSS-MRI Substudy Investigators, Ischemic brain lesions after carotid artery stenting increase future cerebrovascular risk, J Am Coll Cardiol, 2015, 65, 6, 521-529, doi: 10.1016/j.jacc.2014.11.038.

  18. Results

    Featherstone RL, Dobson J, Ederle J, Doig D, Bonati LH, Morris S, Patel NV, Brown MM, Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): a randomised controlled trial with cost-effectiveness analysis, Health Technol Assess, 2016, 20, 20, 1-94, doi: 10.3310/hta20200.

  19. Results

    Doig D, Turner EL, Dobson J, Featherstone RL, de Borst GJ, Stansby G, Beard JD, Engelter ST, Richards T, Brown MM; ICSS Investigators, Risk Factors For Stroke, Myocardial Infarction, or Death Following Carotid Endarterectomy: Results From the International Carotid Stenting Study, Eur J Vasc Endovasc Surg, 2015 , 50, 6, 688-694, doi: 10.1016/j.ejvs.2015.08.006.

  20. Results

    Doig D, Hobson BM, Müller M, Jäger HR, Featherstone RL, Brown MM, Bonati LH, Richards T; ICSS-MRI Study Investigators, Carotid Anatomy Does Not Predict the Risk of New Ischaemic Brain Lesions on Diffusion-Weighted Imaging after Carotid Artery Stenting in the ICSS-MRI Substudy, Eur J Vasc Endovasc Surg, 2016 , 51, 1, 14-20, doi: 10.1016/j.ejvs.2015.08.012.

Additional files

Editorial Notes

05/05/2016: Publication reference added. 29/04/2016: Publication reference added. 18/03/2016: Publication reference added.