Condition category
Circulatory System
Date applied
26/08/2008
Date assigned
09/10/2008
Last edited
30/09/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims.
Patients who are immobile due to illness are at increased risk of developing blood clots in the veins of their legs. These are called deep vein thrombosis or DVT for short. Although patients may experience pain, swelling and redness of their leg associated with these clots, they may not have any symptoms. However, even if they have no symptoms these DVTs can be very dangerous. The clot may break into pieces and be carried to the lungs and heart (called pulmonary embolism) where they can cause the heart to stop. Some patients die suddenly from pulmonary embolism. Patients who are admitted to hospital with a stroke are at particular risk since they are often immobile. Although blood thinning drugs can help reduce the risk of the clots, their benefits are offset by an increased risk of bleeding complications. The CLOTS 1 trial showed that graduated compression stockings (like fight socks) do not reduce the risk of DVT in stroke patients. The CLOTS 3 trial is testing whether Intermittent Pneumatic Compression (called IPC for short) reduces the risk of DVT, pulmonary embolism and death. IPC involves wrapping inflatable sleeves around the legs. These contain air sacs which are inflated, first around the calf, and then the thigh. The squeezing of the leg increases blood flow in the veins and this may reduce the risk of clots forming. The sleeves are attached to an electric air pump at the bedside via tubing. IPC has been shown to reduce the risk of DVT in patients undergoing surgery, but not in patients with other medical conditions including stroke. The aim of the CLOTS 3 trial is to test whether IPC reduces the risk of DVT in patients who are admitted to hospital with a stroke and who are immobile.

Who can participate?
Patients over 16 years old, who are admitted to one of the 105 participating hospitals in the UK, and who have had a stroke and are immobile can be recruited by their doctors and nurses into the trial.

What does the study involve?
Once the patient, or someone close to them, has consented to participating in the trial, the patient's details are entered into a computer. The patient is randomly allocated to wear the IPC for up to 30 days, or not. All recruited patients, whether they wear the IPC or not then have ultrasound scans of their legs at one week and four weeks to detect any DVT. The patients are followed up for six months to establish how well they recover. All other treatments are the same in the patients wearing IPC or not.

What are the possible benefits and risks of participating?
The benefits of participating are that the patients have scans which may detect a clot. These can then be treated with anticoagulants. This may reduce the risk of serious complications. Also, patients in the trial benefit from routine follow up at six months which can identify other post stroke problems such as depression and pain. Apart from the inconvenience of participating in the trial the risks are probably small. In theory the IPC could cause skins problems and the tubing might trip the patient up if they try to walk resulting in injuries.

Where is the study run from?
The study is run by a team in the University of Edinburgh, based at the Western General Hospital in Edinburgh, Scotland.

When is the study starting and how long is it expected to run for?
The first patient of the 2876 patients recruited was recruited in December 2008 and the last in September 2012. The follow up was completed in March 2013, and the results will be available in May 2013.

Who is funding the study?
The main funder was the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) board of the UK. The Chief Scientist Office of the Scottish Government funded the start up phase. Covidien supplied the centres with their IPC sleeves and pumps (Kendallâ„¢ SCD Express Sequential Compression System). Staff funded by the UK stroke research network ran the trial in the 105 UK centres.

Who is the main contact?
Prof Martin Dennis, Professor of stroke medicine, University of Edinburgh.

Trial website

http://www.clotstrial.com

Contact information

Type

Scientific

Primary contact

Prof Martin Dennis

ORCID ID

Contact details

Bramwell Dott Building
Division of Clinical Neurosciences
Western General Hospital
Crere Road
Edinburgh
EH4 2XU
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00789542

Protocol/serial number

HTA 08/14/03; Version 2

Study information

Scientific title

A randomised trial to establish the effectiveness of intermittent pneumatic compression to prevent post stroke deep vein thrombosis (DVT)

Acronym

CLOTS-3

Study hypothesis

Does early and routine application of intermittent pneumatic compression (IPC) in addition to routine care reduce the risk of above knee deep vein thrombosis (DVT) in the weeks following an acute stroke?

More details can be found at http://www.nets.nihr.ac.uk/projects/hta/081403
Protocol at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0005/52394/PRO-08-14-03.pdf

Please note that as of 20/05/2010 this record has been updated to reflect changes in the trial protocol from Version 1 to Version 2. Point 3 of the original exclusion criteria has been removed, this and all updates can be found in the relevant field under the above update date. Please also note that this trial has been extended. The overall trial end date has been changed from 30/04/2013 to 30/09/2014.

On 20/03/2013 the overall trial end date was updated from 30/09/2014 to 31/03/2013.

Ethics approval

1. MREC Scotland, 25/09/2008, ref: 08/MRE00/73
2. Additional approval for England and Wales obtained on 26/08/2008, ref: 08/H0906/137

Study design

Multi-centre randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Information for patients may be found at http://www.dcn.ed.ac.uk/clots/clots_patient_area/index.html

Condition

Stroke

Intervention

Routine care vs routine care plus IPC sleeves. If allocated to the intervention group, thigh length IPC sleeves should be applied to both legs for 30 days.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Presence of definite or probable symptomatic or asymptomatic DVT in the popliteal or femoral veins detected on a screening Compression Doppler ultrasound scan or any symptomatic DVT in the popliteal or femoral veins confirmed on Compression Doppler ultrasound, contrast venography or magnetic resonance imaging (MRI) direct thrombus imaging within 30 days of randomisation.

Secondary outcome measures

In hospital:
1. Death within 30 days
2. Presence of definite or probable DVT in the popliteal or femoral veins detected on a screening Compression Doppler ultrasound scan which had not been suspected clinically before the scan (see below)
3. Definite (i.e. excluding probable DVTs) symptomatic or asymptomatic DVT in the popliteal or femoral veins detected on either a Compression Doppler ultrasound scan, contrast venography or MRI direct thrombus imaging within 30 days of randomisation
4. Any definite or probable symptomatic or asymptomatic DVT (i.e. including DVTs which only involve the calf veins)
5. Confirmed fatal or non-fatal pulmonary embolism (PE)
6. Adherence to allocated treatment

At 6 months:
7. Death from any cause
8. Any confirmed symptomatic or asymptomatic DVT or PE occurring between randomisation and final follow up
9. Any symptomatic DVT or PE occurring between randomisation and final follow up
10. Place of residence
11. Post DVT syndrome
12. Disability (modified Rankin)
13. Health related quality of life (EuroQol). The later effects of DVT/PE (e.g., breathlessness, leg pain or swelling, poor stroke recovery) or the adverse events related to IPC (falls with injury, fractures, skin ulceration, amputation, loss of mobility) may be diverse, so it seems sensible to include a measure of overall health related quality of life.

Overall trial start date

01/12/2008

Overall trial end date

31/03/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients (both males and females) who were admitted to hospital within 3 days of a clinical stroke fulfilling the World Health Organization (WHO) criteria
2. Those who are not able to get up from a chair/out of bed and walk to the toilet without the help of another person

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

2,000

Participant exclusion criteria

Current information as of 20/05/2010:
1. Patients with stroke due to subarachnoid haemorrhage
2. Patients who, in the opinion of the responsible clinician/nurse, are unlikely to benefit from IPC
3. Patients with contraindications for the use of IPC
4. Patients who already have swelling or other signs of an existing DVT. Such patients may be recruited once a DVT has been excluded by normal D Dimers or Compression Doppler ultrasound.
5. Patients under 16 years of age

Initial information at time of registration:
1. Patients with stroke due to subarachnoid haemorrhage
2. Patients who, in the opinion of the responsible clinician/nurse, are unlikely to benefit from IPC
3. Patients who are anticoagulated (taking warfarin, unfractionated heparin, low molecular weight heparin or direct thrombin inhibitors) at the time of enrolment in whom it is planned to continue the anticoagulation throughout the first week or two after the stroke
4. Patients with contraindications for the use of IPC
5. Patients who already have swelling or other signs of an existing DVT. Such patients may be recruited once a DVT has been excluded by normal D Dimers or Compression Doppler ultrasound.
6. Patients under 16 years of age

Recruitment start date

01/12/2008

Recruitment end date

01/09/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Western General Hospital
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

105 participating hospitals
-
United Kingdom

Sponsor information

Organisation

University of Edinburgh (UK)

Sponsor details

Edinburgh Clinical Trials Unit
Queens Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

University/education

Website

http://www.ed.ac.uk

Organisation

Lothian NHS Board (UK)

Sponsor details

Deaconess House
148 Pleasance
Edinburgh
EH8 9RS
United Kingdom

Sponsor type

Government

Website

http://www.nhslothian.scot.nhs.uk

Funders

Funder type

Government

Funder name

Chief Scientist Office (UK) (ref: CZG\2\378)

Alternative name(s)

CSO

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

United Kingdom

Funder name

Added 20/05/10:

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

NIHR Health Technology Assessment Programme - HTA (UK) (ref: 08/14/03)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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. 2012 protocol in http://www.ncbi.nlm.nih.gov/pubmed/22400901
2. 2013 statistical analysis plan in http://www.ncbi.nlm.nih.gov/pubmed/23497465
3. 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23727163
4. 2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26418530

Publication citations

  1. Protocol

    Dennis M, Sandercock P, Reid J, Graham C, Forbes J, , Does intermittent pneumatic compression reduce the risk of post stroke deep vein thrombosis? The CLOTS 3 trial: study protocol for a randomized controlled trial., Trials, 2012, 13, 26, doi: 10.1186/1745-6215-13-26.

  2. Statistical analysis plan

    Dennis M, Sandercock P, Murray G, Forbes J, , Does intermittent pneumatic compression reduce the risk of post stroke deep vein thrombosis? The CLOTS 3 trial: statistical analysis plan., Trials, 2013, 14, 66, doi: 10.1186/1745-6215-14-66.

  3. Results

    , Dennis M, Sandercock P, Reid J, Graham C, Forbes J, Murray G, Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial., Lancet, 2013, 382, 9891, 516-524, doi: 10.1016/S0140-6736(13)61050-8.

  4. Results

    Dennis M, Sandercock P, Graham C, Forbes J, The Clots in Legs Or sTockings after Stroke (CLOTS) 3 trial: a randomised controlled trial to determine whether or not intermittent pneumatic compression reduces the risk of post-stroke deep vein thrombosis and to estimate its cost-effectiveness, Health Technol Assess, 2015 , 19, 76, 1-90.

Additional files

Editorial Notes