The CLOTS trials - Clots in Legs Or sTockings after Stroke (2015)

CLOTS was a family of multicentre randomised controlled trials testing external compression devices (e.g.stockings and intermittent pneumatic compression) for deep vein thrombosis (DVT) prevention in acute stroke patients.

CLOTS trial logo

Trial dates

2001-2015

The CLOTS trial collaboration

Principal Investigator: Prof Martin Dennis

CLOTS Trial Co-ordinating Centre: G Cranswick, A Deary, A Fraser, C Graham, S Grant, A Gunkel, J Hunter, A MacRae, D Perry, V Soosay, C Williams, A Williamson, A Young.
Writing Group: M Dennis (Chair), P A G Sandercock, J Reid, C Graham, G Murray, G Venables, A Rudd, G Bowler.
Trial Steering Committee: G Cranswick, M Dennis, C Graham, S Lewis, G Murray, J Reid, A Rudd, P A G Sandercock, G Venables (Chair), G Bowler, and observers from the MRC and Tyco Healthcare (Covidien).
National Co-ordinators: M G Celani, S Ricci (Italy); R Lindley (Australia).
Auditors/Translators: M G Celani (translation), M Hautvast (data audit) M Paterson (data audit), J Reid (audit of positive DVT evidence), T Ting (translation).
Independent Data Monitoring Committee C Baigent (Oxford), J Bamford (Leeds, Chair), J Slattery (London).
 

Summary & findings

The CLOTS study aimed to find out whether graduated compression stockings or Intermittent Pneumatic Compression sleeves reduce the risk of a person admitted to hospital with a stroke developing a deep vein thrombosis (DVT).

The CLOTS study comprised three trials comparing alternative treatments:

Trial 1: Long stockings vs. No stockings

  • This trial aimed to test whether thigh-length graduated compression stockings reduce the risk of developing a blood clot in the veins of the legs after a stroke. 2518 patients were enrolled from 64 centres in the UK, Italy, and Australia.
  • The data indicated that stockings do not reduce the risk of clots (DVT) in patients admitted to hospital with a stroke.

Trial 2: Long stockings vs. Short Stockings

  • The second CLOTS trial investigated whether long graduated compression stockings reduced the risk of developing a deep vein thrombosis (DVT) compared to short knee-length graduated compression stockings in patients admitted with a stroke. 3114 patients were recruited from 112 hospitals in 9 countries. The primary outcome was symptomatic or asymptomatic DVT in the popliteal or femoral veins, detected on a scan at 7-10 days or 25-30 days.
  • The trial found that proximal DVT occurs more often in patients with stroke who wear below-knee stockings than in those who wear thigh-length stockings.

Trial 3: Intermittent Pneumatic Compression (IPC) vs. No IPC

  • CLOTS3 compared Intermittent Pneumatic Compression (IPC) with No IPC.  2876 patients were recruited at 94 hospitals in the UK. Participants were allocated to routine care or routine care plus IPC for 30 days, or untilearlier discharge or walking independently.
  • The data showed that IPC reduced the risk of DVT by about a third compared with the risk in patients who received routine care only. IPC was shown to be an effective and inexpensive method of reducing the risk of DVT and improving survival in immobile stroke patients.
  • ISCRCTN registration number: 93529999

 

CLOTS1 and CLOTS2 protocol (295.46 KB / PDF)
CLOTS3 full protocol (726.93 KB / PDF)
CLOTS3 protocol summary (51.01 KB / PDF)
CLOTS3 results poster (210.53 KB / PDF)

Impact

Photo of a nurse putting compression stockings on a patient

In 2013, it was assessed that the CLOTS1 and 2 trial findings had resulted in approximately 6000 fewer complications (e.g., skin breaks) in the UK. Stocking use had decreased by 95%, which had saved the NHS in excess of £20M per annum.

Research impact (University of Edinburgh College of Medicine and Veterinary Medicine): Compression stocking research improves care of stroke patients

Research Excellence Framework 2014 Impact Case Study: Graduated compression stockings do not reduce the risk of post-stroke deep vein thrombosis [external link]

 

Media coverage

CLOTS1 - The Scotsman (127.81 KB / PDF)
CLOTS1 - Washington Post (60.92 KB / PDF)
CLOTS1 - Nursing Times (52.93 KB / PDF)
CLOTS1 - NHS Choices (56.18 KB / PDF)

CLOTS2: Study gets measure of blood clots. University of Edinburgh website 2010

CLOTS3: Leg wraps raise hopes of saved lives after strokes. BBC News website May 2013

CLOTS3: Inflatable stockings could save many stroke patients. BBC News (video) May 2013

CLOTS3:  Hope for stroke patients. University of Edinburgh website April 2013

 

Publications

1: Dennis M, Sandercock P, Graham C, Forbes J; CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration, Smith 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 Sep;19(76):1-90. doi: 10.3310/hta19760.

2: Dennis M, Graham C, Smith J, Forbes J, Sandercock P; CLOTS trial collaboration. Which stroke patients gain most from intermittent pneumatic compression: further analyses of the CLOTS 3 trial. Int J Stroke. 2015 Oct;10 Suppl A100:103-7. doi: 10.1111/ijs.12598. Epub 2015 Aug 26.

3: CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effect of intermittent pneumatic compression on disability, living circumstances, quality of life, and hospital costs after stroke: secondary analyses from CLOTS 3, a randomised trial. Lancet Neurol. 2014 Dec;13(12):1186-92. doi: 10.1016/S1474-4422(14)70258-3. Epub 2014 Oct 31.

4: CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration, 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 Aug 10;382(9891):516-24. doi: 10.1016/S0140-6736(13)61050-8. Epub 2013 May 31. Erratum in: Lancet. 2013 Aug 10;382(9891):506. Erratum in: Lancet. 2013 Sep 21;382(9897):1020.

5: CLOTS Trials Collaboration, Dennis M, Sandercock P, Reid J, Graham C, Murray G, Venables G, Rudd A, Bowler G. The effect of graduated compression stockings on long-term outcomes after stroke: the CLOTS trials 1 and 2. Stroke. 2013 Apr;44(4):1075-9. doi: 10.1161/STROKEAHA.111.680298. Epub 2013 Mar 12.

6: Dennis M, Sandercock P, Murray G, Forbes J; CLOTS Trials Collaboration. Does intermittent pneumatic compression reduce the risk of post stroke deep vein thrombosis? The CLOTS 3 trial: statistical analysis plan. Trials. 2013 Mar 6;14:66. doi: 10.1186/1745-6215-14-66.

7: Ankolekar S, Renton C, Bereczki D, Sprigg N, Payne T, Gommans J, Berge E, Wardlaw J, Dennis MS, Bath PM; ENOS Trial Investigators. Effect of the neutral CLOTS 1 trial on the use of graduated compression stockings in the Efficacy of Nitric Oxide Stroke (ENOS) trial. J Neurol Neurosurg Psychiatry. 2013 Mar;84(3):342-7. doi: 10.1136/jnnp-2012-303396. Epub 2012 Oct 31.

8: Dennis M, Sandercock P, Reid J, Graham C, Forbes J; CLOTS Trials Collaboration. 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 Mar 8;13:26. doi: 10.1186/1745-6215-13-26.

9: Dennis M, Mordi N, Graham C, Sandercock P; CLOTS trials collaboration. The timing, extent, progression and regression of deep vein thrombosis in immobile stroke patients: observational data from the CLOTS multicenter randomized trials. J Thromb Haemost. 2011 Nov;9(11):2193-200. doi: 10.1111/j.1538-7836.2011.04486.x.

10: Dennis M, Sandercock P, Reid J, Graham C, Murray G, Venables G, Rudd A, Bowler G; CLOTS Trials Collaboration. Can clinical features distinguish between immobile patients with stroke at high and low risk of deep vein thrombosis? Statistical modelling based on the CLOTS trials cohorts. J Neurol Neurosurg Psychiatry. 2011 Oct;82(10):1067-73. doi: 10.1136/jnnp.2010.235945. Epub 2011 Feb 28.

11. CLOTS (Clots in Legs Or sTockings after Stroke) Trial Collaboration. Thigh-length versus below-knee stockings for deep venous thrombosis prophylaxis after stroke: a randomized trial. Ann Intern Med. 2010 Nov 2;153(9):553-62. doi: 10.7326/0003-4819-153-9-201011020-00280. Epub 2010 Sep 20. Erratum in: Ann Intern Med. 2010 Dec 21;153(12):851.

12: CLOTS Trials Collaboration, Dennis M, Sandercock PA, Reid J, Graham C, Murray G, Venables G, Rudd A, Bowler G. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial. Lancet. 2009 Jun 6;373(9679):1958-65. doi: 10.1016/S0140-6736(09)60941-7. Epub 2009 May 26.

Funding

The CLOTS Trials were funded by research grants from the Chief Scientist Office of the Scottish Government, Chest Heart and Stroke Scotland and the Medical Research Council of the UK. Covidien provided the centers with supplies of T.E.D. Anti-embolism Stockings.

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