The SOX Trial: Compression Stockings to Prevent the Post-Thrombotic Syndrome

The SOX Trial: Compression Stockings to Prevent the Post-Thrombotic Syndrome After Symptomatic Proximal Deep Venous Thrombosis

The purpose of this study is to determine whether elastic compression stockings used for 2 years are effective in preventing the post-thrombotic syndrome in patients with symptomatic proximal deep venous thrombosis.

Study Overview

• Status: Completed
• Conditions: Deep Venous Thrombosis
• Intervention / Treatment: Device: Knee-length, graduated elastic compression stocking; Device: Knee-length, placebo stocking

Detailed Description

The post-thrombotic syndrome (PTS) is a frequent, burdensome and costly condition that occurs in about one third of patients after an episode of deep vein thrombosis (DVT). Affected patients have chronic leg pain and swelling, and sometimes develop skin ulcers. At present, there is little to offer for the treatment of this condition. Prevention of PTS is the key to reducing its burden on patients and society. Elastic compression stockings (ECS) could be helpful in preventing PTS, however data on their effectiveness are scarce and conflicting.

Comparison(s): Knee-length, 30-40 mm Hg (Class II), graduated ECS worn on the DVT-affected leg daily for 2 years compared to knee-length, inactive (i.e. no compression) stocking, identical in appearance to active ECS, worn on the DVT-affected leg daily for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 806
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 4R2
      • Victoria Heart Institute Foundation
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • QE II Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences - General Hospital
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences - Chedoke Division
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences - McMaster University Medical Centre
    • Hamilton, Ontario, Canada, L8V 1C3
      • Hamilton Health Sciences - Henderson General Hospital
    • Hamilton, Ontario, Canada, L8P 3B6
      • St. Joseph's Healthcare Hamilton
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital, Civic Campus
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook & Women's College Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network - Toronto General Hospital
  • Quebec
    • Longueuil, Quebec, Canada, J4M 2A5
      • Centre Hospitalier Pierre-Boucher
    • Montreal, Quebec, Canada, H4J 1C5
      • Hôpital du Sacré-Coeur de Montréal
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B. Davis - Jewish General Hospital
    • Montreal, Quebec, Canada, H3T 1M5
      • St. Mary's Hospital Center
    • Montreal, Quebec, Canada, H2L 4M1
      • Centre Hospitalier de L'Universite de Montreal - Hôpital Notre-Dame
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Université de Montréal - Hôpital Hôtel-Dieu
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital - McGill University Health Centre
    • Montreal, Quebec, Canada, H4G 1A4
      • Montreal General Hospital - McGill University Health Centre
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Centre hospitalier affilié universitaire de Québec, Hôpital de l'Enfant-Jésus
• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health Systerm
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consecutive patients with a first, symptomatic, objectively confirmed proximal DVT diagnosed within the last 14 days (with or without concurrent distal DVT or pulmonary embolism)
• Who have no contraindications to standard treatment with heparin and/or warfarin, and
• Who provide informed consent to participate

Exclusion Criteria:

• Contraindication to compression stockings
• Limited lifespan (estimated < 6 months)
• Geographic inaccessibility preventing return for follow-up visits
• Inability to apply stockings daily and unavailability of a caregiver to apply stockings daily
• Treatment of acute DVT with thrombolytic agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active ECS; Active Elastic Compression Stockings (ECS) 30-40 mm Hg compression at the ankle.	Device: Knee-length, graduated elastic compression stocking; Worn daily for 2 years, 30-40 mm Hg
PLACEBO_COMPARATOR: Placebo ECS; Placebo stockings with identical appearance to Active ECS and with < 5 mm Hg compression at the ankle.	Device: Knee-length, placebo stocking; Worn daily for two years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Post-thrombotic Syndrome (PTS)	During 2-year follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of PTS, Including Incidence of Venous Ulcer	Highest Villalta at or after 6 month visit The Villalta Scale for assessment of the post-thrombotic syndrome The Villalta scale has a range of 0-33. A Villalta scale score >4 indicates post-thrombotic syndrome (severity of post-thrombotic syndrome is categorized as 5-9 points, mild; 10-14 points, moderate; >14 points or presence of an ulcer, severe). Higher values signify worse outcome. Points on each item in the scale are simply summed to a total score.	6-24 months.
Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding		During 2-year follow up
Quality of Life	The SF-36 is a well-validated generic quality-of-life (QOL) instrument. It includes questions on both physical and mental health. Higher scores indicate a better QOL. The VEINES-QOL is a venous-disease specific QOL measure that consists of 25 items that quantify venous disease effect on QOL, and an embedded symptom sub-questionnaire (VEINES-Sym) with 10 items that measures venous symptoms. Higher scores are associated with better QOL. The VEINES-QOL/Sym and SF-36 use the standard method for scoring questionnaires with items with different response scales that is now routinely used. Raw scores are first transformed to z score equivalents (mean, 0; standard deviation, 1), which then are transformed to T scores (mean, 50; standard deviation, 10) to give an easily understood range of scores. A person-specific estimate is imputed for any missing item in cases where the patient answered at least 50% of the items in the scale.	24 months

Collaborators and Investigators

• Sponsor: Sir Mortimer B. Davis - Jewish General Hospital
• Collaborators: Canadian Institutes of Health Research (CIHR); Sigvaris Corporation

Publications and helpful links

General Publications

• Kahn SR, Shbaklo H, Shapiro S, Wells PS, Kovacs MJ, Rodger MA, Anderson DR, Ginsberg JS, Johri M, Tagalakis V; SOX Trial Investigators. Effectiveness of compression stockings to prevent the post-thrombotic syndrome (the SOX Trial and Bio-SOX biomarker substudy): a randomized controlled trial. BMC Cardiovasc Disord. 2007 Jul 24;7:21. doi: 10.1186/1471-2261-7-21.
• Kahn SR, Shapiro S, Wells PS, Rodger MA, Kovacs MJ, Anderson DR, Tagalakis V, Houweling AH, Ducruet T, Holcroft C, Johri M, Solymoss S, Miron MJ, Yeo E, Smith R, Schulman S, Kassis J, Kearon C, Chagnon I, Wong T, Demers C, Hanmiah R, Kaatz S, Selby R, Rathbun S, Desmarais S, Opatrny L, Ortel TL, Ginsberg JS; SOX trial investigators. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet. 2014 Mar 8;383(9920):880-8. doi: 10.1016/S0140-6736(13)61902-9. Epub 2013 Dec 6.
• Kahn SR, Shapiro S, Ducruet T, Wells PS, Rodger MA, Kovacs MJ, Anderson D, Tagalakis V, Morrison DR, Solymoss S, Miron MJ, Yeo E, Smith R, Schulman S, Kassis J, Kearon C, Chagnon I, Wong T, Demers C, Hanmiah R, Kaatz S, Selby R, Rathbun S, Desmarais S, Opatrny L, Ortel TL, Galanaud JP, Ginsberg JS. Graduated compression stockings to treat acute leg pain associated with proximal DVT. A randomised controlled trial. Thromb Haemost. 2014 Dec;112(6):1137-41. doi: 10.1160/TH14-05-0430. Epub 2014 Aug 28.

Helpful Links

• Biomarker Sub Study of the Compression Stockings to Prevent the Post-Thrombotic Syndrome (SOX) Trial (Bio-SOX)

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (ACTUAL): February 1, 2012
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: September 1, 2005
• First Submitted That Met QC Criteria: September 1, 2005
• First Posted (ESTIMATE): September 2, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): August 18, 2014
• Last Update Submitted That Met QC Criteria: August 15, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Quality of Life; Randomized Controlled Trials; Postphlebitic Syndrome; Post-Thrombotic Syndrome; Stockings, Compression; Elastic Stockings
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease; Embolism and Thrombosis; Peripheral Vascular Diseases; Venous Insufficiency; Phlebitis; Syndrome; Thrombosis; Venous Thrombosis; Postthrombotic Syndrome; Postphlebitic Syndrome
• Other Study ID Numbers: MCT-63142; ISRCTN71334751 (REGISTRY: ISRCTN)