Elastic Compression Stockings for Prevention of Post-thrombotic Syndrome (CELEST)
Post thrombotic syndrome (PTS) is a frequent and burdensome complication of proximal deep-vein thrombosis.Therapeutic options for PTS are limited and mainly rely on its prevention. Therapeutic trials evidenced that elastic compression stockings (ECS) applying 30-40mmHg of pressure at the ankle reduced the rate of PTS by 50%. Although ECS are unlikely to cause harm, in clinical practice, compliance to this treatment appears to be low as ECS may be difficult to apply and to wear.
ECS with a lighter compression strength (20-30mmHg) might be easier to apply and be more comfortable. This could favor a better compliance.
CELEST is a randomized, multicentre, double-blind trial which aims to determine whether ECS applying 25mmHg of targeted pressure at the ankle are non inferior to ECS applying 35mmHg of targeted pressure at the ankle
|Deep Vein Thrombosis Post-thrombotic Syndrome||Device: 25mmHg ECS Device: 35 mmHg ECS|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Evaluation of the Efficacy of Elastic Compression in Preventing Post-thrombotic Syndrome. Randomised Non-inferiority Study for Ankle Pressure Targeted at 25 mm Hg Versus 35 mm Hg|
- To show that elastic compression with ankle pressure targeted at 25 mm Hg is not inferior in preventing the onset of clinical post-thrombotic syndrome to a target ankle pressure of 35 mm Hg (recommended pressure being greater than 30 mm Hg) [ Time Frame: 24 months ]cumulative incidence 24 months after inclusion of PTS apparition defined by the Villalta score > or equal to 5. A visual guide will be given to investigators to assist them and standardize PTS evaluation. Investigators will receive a Villalta training during set up visits.
- superiority of targeted pressure at 35 mm Hg for compliant patients. Analysis of the primary endpoint per protocol amongst patients responding to the definition of compliance for compression scheduled by randomization [ Time Frame: 24 months ]analysis of primary endpoint (cumulative incidence of PTS) amongst patients responding to the definition of observance for compression scheduled by randomization. It means a per protocol analysis. The per protocol analysis defined as follow : patients ideally compliant (see next secondary outcome measure with self declaration of compression carrying superior or equal to 80 % especially)and patients with respect to randomization.
- Superiority of 25 mm Hg on the therapeutic compliance criterion [ Time Frame: 24 months ]
Superiority of 25 mm Hg on the therapeutic compliance criterion at 24 months
Compliance is defined by 3 conditions :
- Morisky-Green score adjusted between 0 and 2
because of French clinical practices it should be pertinent to take into consideration 2 compliance type :
- ideal compliance : Self declaration ≥ 80 % (reference PRANDONI)
- adequate compliance : self declaration between 50 and 79% for (French references Delluc and Optimev study)
- return of used stockings ≥ to 80%
- superiority of 25 mm Hg for constraints related to compression and chronic venous insufficiency quality of life (CIVIQ) [ Time Frame: 3 months, 12 months, 24 months ]CIVIQ quality of life (CIVIQ 20) specific to chronic venous insufficiency at 3 months, 12 months and 24 months and questionnaire about constraints of compression stockings.
- non inferiority of 25 mm Hg for the comparative evaluation of the symptomatic effect of short-term compression (pain, sensation of oedema) form baseline to 3 months [ Time Frame: 3 months ]Comparison of evolution at short-term (3 months) of venous thrombosis symptoms (pain, oedema feeling). Self assessment by VAS of pain and oedema feeling once a week during 3 months. Assessment by the investigator at inclusion and during visit at 3 months (ankle measurement, clinical signs) will be done also. A statistical analysis will be done as soon as 3 months follow up data will be verified to evaluate symptoms evolution due to deep venous thrombosis.
- Non-inferiority of 25 mm Hg for changes in overall quality of life evaluated on the basis of the EUROQUOL questionnaire [ Time Frame: 3months, 12 months, 24 months ]Non-inferiority of 25 mm Hg for changes in overall quality of life evaluated on the basis of the EUROQUOL questionnaire (EQ5D)
- non inferiority of 25 mm Hg for the intensity of long term chronic venous insufficiency symptoms (12 months and 24 months) [ Time Frame: 12 and 24 months ]
Long term assessment of evolution and intensity of symptoms (pain, oedema feeling) related to potential post-thrombotic syndrome apparition
- Monthly self-assessment by VAS for pain and oedema feeling during 24 months. It will be done at the end of each month and will focus on symptoms intensity (last week of the month)
- An assessment will be done by investigator, in addition of previous criterion, at 12 and 24 months
- Assessment with the Ginsberg score (interview by the investigator at 12 and 24 months)
- Comparison of averages on Villalta score (quantitative)
- non inferiority of 25 mm Hg for the onset of permanent trophic disorders [ Time Frame: 3 months, 12 and 24 months ]CEAP classification evaluated by investigator at 3, 12 and 24 months
- non inferiority of 25 mm Hg for the onset of sequalae or post thrombotic residues on an duplex scan at 3 months, 12 and 24 months [ Time Frame: 3, 12 and 24 months ]
Assessment by duplex scan of deep and superficial veins at 3, 12 and 24 months
- Assessment by duplex scan of deep reflux (>1s in femoral vein, and/or popliteal vein, tibio peroneal trunck)
- Assessment by duplex scan of superficial reflux (> 0.5s in great saphenous vein, small saphenous vein, perforating veins)
- Assessment by echographic score of thickness and location of residual thrombus
- Assessment by duplex scan of re-canalization of collectors trunks and/or parietal sequalae
- testing for the prognostic factors of the onset post thrombotic syndrome and comparison of the onset kinetics of post thrombotic syndrome [ Time Frame: 24 months ]
variables tested as prognostic factors of post thrombotic syndrome apparition :
- location of the upper pole of thrombus
- kinetic of thrombus lysis by duplex scan at 3 months
- Idiopathic nature of TED
- Delay of diagnostic of deep venous thrombosis
- Initial intensity of deep venous thrombosis symptoms
- Initial evolution of symptoms of deep venous thrombosis between J0 and 3 months
- Persistence of the symptoms at 3 months
- Patient's characteristics
- Kinetic of of Villalta score apparition ≥ 5 by survival curve
- Kinetic of post thrombotic syndrome apparition by Villalta score
- test for key factors in good compliance [ Time Frame: 24 months ]Compliance evaluation according to the 3 axes defined on third outcome measure and research of determinants of good compliance by specific questionnaire
- Adverse events [ Time Frame: 24 months ]description and comparison of the incidence of adverse events including unexpected adverse events, events expected with this type of disease (recurrence of the venous thromboembolic disease, recurrence of deep vein thrombosis, pulmonary embolism, superficial venous thrombosis, venous ulcer) and events possibly related to the study treatment (arterial decompensation passing to Lerich stage III or IV, skin intolerance)
- Subgroups analysis of the primary objective and secondary objectives according to the gender stratification criterion and age [ Time Frame: 24 months ]Stratification on age (more or less than 65 years-old) for testing the hypothesis by subgroups analysis of the benefit of a better adaptation of compression 25 mm Hg on older subjects, as suggested by S. Khan.
- superiority of 25 mmHg on 35 mmHg in preventing the onset of clinical post thrombotic syndrome [ Time Frame: 24 months ]superiority of 25 mmHg on 35 mmHg in preventing the onset of clinical post thrombotic syndrome. Outcome measure identical to primary endpoint
- sensitivity analysis of primary endpoint excluding patients with a differential diagnosis can explain a Villalta score ≥ 5 [ Time Frame: 24 months ]sensitivity analysis of primary endpoint excluding patients with a differential diagnosis which could explain a Villalta score ≥ 5. Outcome measure identical to primary endpoint
|Actual Study Start Date:||June 2012|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||July 2019 (Final data collection date for primary outcome measure)|
Experimental: 25mmHg ECS
Thigh-length graduated elastic compression stockings applying 25mmhg of targeted pressure at the ankle worn daily for two years
Device: 25mmHg ECS
Thigh-length graduated elastic compression stockings applying 25 mmhg of targeted pressure at the ankle worn daily (from morning to night) for two years.
Before receiving the randomly allocated treatment, each patient will wear cotton, class III Varisma Comfort® stay-up stockings (20-36 mm Hg).
Active Comparator: 35mmHg ECS
Thigh-length graduated elastic compression stockings applying 35 mmhg of targeted pressure at the ankle worn daily for two years
Device: 35 mmHg ECS
Thigh-length graduated elastic compression stockings applying 35mmhg of pressure at the ankle worn daily (from morning to night) for two years Before receiving the randomly allocated treatment, each patient will wear cotton, class III Varisma Comfort® stay-up stockings (20-36 mm Hg).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01578122
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|Principal Investigator:||Jean-Luc BOSSON, MD, PhD||CIC Grenoble|