Deep Venous Thrombosis
Conditions
Keywords
Postphlebitic Syndrome, Post-Thrombotic Syndrome, Elastic Stockings, Stockings, Compression, Randomized Controlled Trials, Quality of Life
Brief summary
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.
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.
Interventions
DEVICEKnee-length, graduated elastic compression stocking
Worn daily for 2 years, 30-40 mm Hg
DEVICEKnee-length, placebo stocking
Worn daily for two years
Sponsors
Canadian Institutes of Health Research (CIHR)
Sigvaris Corporation
Sir Mortimer B. Davis - Jewish General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Post-thrombotic Syndrome (PTS) | During 2-year follow up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding | During 2-year follow up | — |
| Severity of PTS, Including Incidence of Venous Ulcer | 6-24 months. | 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. |
| Quality of Life | 24 months | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Between June, 2004, and February, 2010, we enrolled patients in 24 centres in Canada and the USA.
Pre-assignment details
Patients were excluded if they had a contraindication to the use of compression stockings, an expected life span of \<6 months, geographical inaccessibility, were unable to apply stockings, or received thrombolytic therapy for the initial treatment of acute deep vein thrombosis (DVT).
Participants by arm
| Arm | Count |
|---|---|
| Active ECS Active Elastic Compression Stockings. 30-40 mm Hg | 409 |
| Placebo ECS Placebo stockings with identical appearance but less than 5 mm Hg compression at the ankle. | 394 |
| Total | 803 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 36 | 36 |
| Overall Study | Lost to Follow-up | 23 | 21 |
| Overall Study | Withdrawal by Subject | 33 | 37 |
Baseline characteristics
| Characteristic | Placebo ECS | Total | Active ECS |
|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 15.8 | 55.1 years STANDARD_DEVIATION 15.5 | 55.4 years STANDARD_DEVIATION 15.3 |
| Age, Customized 40-65 years | 217 participants | 439 participants | 222 participants |
| Age, Customized <40 years | 67 participants | 134 participants | 67 participants |
| Age, Customized >65 years | 110 participants | 230 participants | 120 participants |
| Body-mass index, kg/m2 | 28.9 kg/m^2 STANDARD_DEVIATION 6.1 | 28.95 kg/m^2 STANDARD_DEVIATION 6.1 | 29.0 kg/m^2 STANDARD_DEVIATION 6.1 |
| Concurrent pulmonary embolism | 57 participants | 114 participants | 57 participants |
| Duration of DVT Treatment Duration of heparin | 8 days | 8 days | 8 days |
| Duration of DVT Treatment Duration of Oral Anti-Coagulation (OAC) | 182 days | 185 days | 186 days |
| Most proximal extent of DVT Common femoral vein | 107 participants | 216 participants | 109 participants |
| Most proximal extent of DVT Femoral Vein | 123 participants | 251 participants | 128 participants |
| Most proximal extent of DVT Iliac vein | 49 participants | 93 participants | 44 participants |
| Most proximal extent of DVT Popliteal vein | 115 participants | 243 participants | 128 participants |
| Outpatients | 344 participants | 699 participants | 355 participants |
| Race/Ethnicity, Customized White ethnic origin | 354 participants | 725 participants | 371 participants |
| Sex: Female, Male Female | 166 Participants | 320 Participants | 154 Participants |
| Sex: Female, Male Male | 228 Participants | 483 Participants | 255 Participants |
| Side of DVT Bilateral | 5 participants | 12 participants | 7 participants |
| Side of DVT Left | 173 participants | 353 participants | 180 participants |
| Side of DVT Right | 216 participants | 438 participants | 222 participants |
| Time from DVT diagnosis to randomization | 4.6 days STANDARD_DEVIATION 3.8 | 4.7 days STANDARD_DEVIATION 3.9 | 4.8 days STANDARD_DEVIATION 4.1 |
| Type of DVT Treatment Investigational anitcoagulant | 11 participants | 26 participants | 15 participants |
| Type of DVT Treatment Low molecular weight heparin | 384 participants | 772 participants | 388 participants |
| Type of DVT Treatment Unfractionated heparin | 21 participants | 52 participants | 31 participants |
| Type of DVT Treatment Warfarin | 317 participants | 647 participants | 330 participants |
| Venous thrombosis risk factors Active cancer | 46 participants | 98 participants | 52 participants |
| Venous thrombosis risk factors Family history of venous thromboembolism | 82 participants | 167 participants | 85 participants |
| Venous thrombosis risk factors Immobilised in past month | 61 participants | 128 participants | 67 participants |
| Venous thrombosis risk factors Pregnant, post partum, OCT, or HRT | 55 participants | 92 participants | 37 participants |
| Venous thrombosis risk factors Surgery, past 3 months | 64 participants | 141 participants | 77 participants |
| Venous thrombosis risk factors Trauma, past 3 months | 51 participants | 93 participants | 42 participants |
| Villalta score at baseline | 8.7 Score on a scale STANDARD_DEVIATION 4.8 | 8.4 Score on a scale STANDARD_DEVIATION 4.6 | 8.2 Score on a scale STANDARD_DEVIATION 4.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 409 | 7 / 394 |
| serious Total, serious adverse events | 0 / 409 | 0 / 394 |
Outcome results
Primary
Incidence of Post-thrombotic Syndrome (PTS)
Time frame: During 2-year follow up
Population: Intention to treat.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active ECS | Incidence of Post-thrombotic Syndrome (PTS) | 44 participants |
| Placebo ECS | Incidence of Post-thrombotic Syndrome (PTS) | 37 participants |
p-value: 0.5895% CI: [0.73, 1.76]Regression, Cox
Secondary
Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding
Time frame: During 2-year follow up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active ECS | Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding | Recurrent venous thromboembolism | 33 participants |
| Active ECS | Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding | Death from VTE | 0 participants |
| Active ECS | Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding | Major bleeding | 11 participants |
| Placebo ECS | Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding | Recurrent venous thromboembolism | 38 participants |
| Placebo ECS | Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding | Death from VTE | 0 participants |
| Placebo ECS | Incidence of Objectively Confirmed Recurrent Venous Thromboembolism (VTE), Death From VTE and Major Bleeding | Major bleeding | 14 participants |
Secondary
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.
Time frame: 24 months
Population: Patients who completed the SF-36 and VEINES-QOL at 24 months follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active ECS | Quality of Life | SF-36 PCS | 46.7 Scores on a scale | Standard Deviation 10.7 |
| Active ECS | Quality of Life | SF-36 MCS | 52.7 Scores on a scale | Standard Deviation 9.3 |
| Active ECS | Quality of Life | VEINES-QOL | 56.6 Scores on a scale | Standard Deviation 5.3 |
| Placebo ECS | Quality of Life | SF-36 PCS | 47.5 Scores on a scale | Standard Deviation 10.2 |
| Placebo ECS | Quality of Life | SF-36 MCS | 52.5 Scores on a scale | Standard Deviation 8.8 |
| Placebo ECS | Quality of Life | VEINES-QOL | 57.4 Scores on a scale | Standard Deviation 5.3 |
Secondary
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.
Time frame: 6-24 months.
Population: Highest Villalta score at or after 6 month visit (missing for 48 patients in each group).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active ECS | Severity of PTS, Including Incidence of Venous Ulcer | None (score <5) | 185 participants |
| Active ECS | Severity of PTS, Including Incidence of Venous Ulcer | Mild (5-9) | 119 participants |
| Active ECS | Severity of PTS, Including Incidence of Venous Ulcer | Moderate (10-14) | 30 participants |
| Active ECS | Severity of PTS, Including Incidence of Venous Ulcer | Severe (>14 or ulcer) | 27 participants |
| Placebo ECS | Severity of PTS, Including Incidence of Venous Ulcer | Severe (>14 or ulcer) | 20 participants |
| Placebo ECS | Severity of PTS, Including Incidence of Venous Ulcer | None (score <5) | 178 participants |
| Placebo ECS | Severity of PTS, Including Incidence of Venous Ulcer | Moderate (10-14) | 37 participants |
| Placebo ECS | Severity of PTS, Including Incidence of Venous Ulcer | Mild (5-9) | 111 participants |