Clinical trial NCT01578122: Elastic Compression Stockings for Prevention of Post-thrombotic Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Deep Vein Thrombosis
Post-thrombotic Syndrome
Keywords: post-thrombotic syndrome
prevention
deep vein thrombosis
elastic compression stockings
compliance
quality of life
Lead sponsor: Laboratoires Innothera
Sponsor class: INDUSTRY
Collaborators: name: University Hospital, Grenoble
name: Floralis
First posted: 2012-04-16
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: CELEST trial is a controlled, randomized, multicentre, non-inferiority 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. Patients with a first acute symptomatic proximal DVT will be randomized to wear for two years either ECS applying 25mmHg of targeted pressure at the ankle or ECS applying 35mmHg of targeted pressure at the ankle. All patients will be prescribed anticoagulants for at least three months. The primary outcome will be the rate of PTS assessed with the Villalta scale in both arms of the study during the 2 years study period. Rate of compliance,severity of PTS and quality of life in both groups will constitute the main secondary outcomes.

Eligibility criteria: Inclusion criteria

* Patient (male/female) at least 18 years old
* Patient presenting with an initial episode of proximal deep vein thrombosis (DVT) confirmed by an additional examination (echo-Doppler scan) taken no more than 8 days previously :

the proximal character defined by a DVT from the collecting trunk extending from the tibial-peroneal trunk to the inferior vena cava inclusive the unilateral character concerns only the proximal part. Patients with a distal DVT on the contralateral member the day of diagnosis can be included The notion of initial episode concerns only the proximal part. Patients with a preceding DVT limited to distal part can be included

* with no trophic disorders at baseline (CEAP class 4, 5 or 6 excluded)
* with or without pulmonary embolism
* Patient capable of benefiting from anticoagulant therapy of at least 3 months duration
* Available to participate in a clinical trial with a 24-month follow-up period and for which a delivery of study products may be possible throughout its participation (delivery possible only in Metropolitan France)
* Life expectancy greater than 24 months
* Volunteer to take part in the study, having signed the consent form after receiving sufficient information and the information leaflet
* Person affiliated to social security or the recipient of a similar scheme.

non inclusion criteria

* Patients with at least one of these contraindications to compression treatment:

  * phlegmasia cerulea dolens,
  * septic thrombosis,
  * product intolerance, allergic reaction to one of the components
  * Arteritis obliterans stage III and IV of the lower limbs (IPS\<0.6),
  * Micro-angiopathy, advanced diabetes,
  * Decompensated heart failure,
  * Skin infections: anti-infective treatment must precede compression therapy,
  * Weeping skin diseases of the leg.
  * Compression treatment technically impossible during the study
* Patients presenting with bilateral venous thrombosis of the lower limbs.
* Patient having received fibrinolytic treatment, mechanical thrombo-aspiration or venous repermeation surgery for venous thrombosis justifying inclusion
* Patients having undergone mechanical interruption of the inferior vena cava.
* Patients for whom long-term elastic compression for the treatment of lymphatic venous insufficiency (patients with lymphoedema), for instance, is indicated prior to DVT. Patients with elastic compression for primary thromboprophylaxis of thromboembolic disease (TED) are eligible.
* Patients presenting with oedema unrelated to venous insufficiency or in whom oedema is likely to develop within 2 years.
* Patients receiving diuretic treatment for more than 3 months due to heart failure.
* Pregnant women
* Person deprived of liberty by a legal or administrative decision, person under legal protection.
* Patient currently participating in a clinical trial or having taken part in a clinical trial in the month preceding inclusion
* Patient presenting with a history of mental or psychiatric illness or any other factor restricting his/her ability to participate in an informed manner and in compliance with the protocol

Primary outcomes:
measure: 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)
timeFrame: 24 months
Secondary outcomes:
measure: 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
timeFrame: 24 months
measure: Superiority of 25 mm Hg on the therapeutic compliance criterion
timeFrame: 24 months
measure: superiority of 25 mm Hg for constraints related to compression and chronic venous insufficiency quality of life (CIVIQ)
timeFrame: 3 months, 12 months, 24 months
measure: 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
timeFrame: 3 months
measure: Non-inferiority of 25 mm Hg for changes in overall quality of life evaluated on the basis of the EUROQUOL questionnaire
timeFrame: 3months, 12 months, 24 months
measure: non inferiority of 25 mm Hg for the intensity of long term chronic venous insufficiency symptoms (12 months and 24 months)
timeFrame: 12 and 24 months
measure: non inferiority of 25 mm Hg for the onset of permanent trophic disorders
timeFrame: 3 months, 12 and 24 months
measure: 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
timeFrame: 3, 12 and 24 months
measure: testing for the prognostic factors of the onset post thrombotic syndrome and comparison of the onset kinetics of post thrombotic syndrome
timeFrame: 24 months
measure: test for key factors in good compliance
timeFrame: 24 months
measure: Adverse events
timeFrame: 24 months
measure: Subgroups analysis of the primary objective and secondary objectives according to the gender stratification criterion and age
timeFrame: 24 months
measure: superiority of 25 mmHg on 35 mmHg in preventing the onset of clinical post thrombotic syndrome
timeFrame: 24 months
measure: sensitivity analysis of primary endpoint excluding patients with a differential diagnosis can explain a Villalta score ≥ 5
timeFrame: 24 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: Cabinet
state: Rhônes Alpes
city: Aix Les Bains
country: France
facility: Cabinet
city: Alencon
country: France
facility: Cabinet
city: Amiens
country: France
facility: Clinique Victor PAUCHET
city: Amiens
country: France
facility: CHRU Amiens
city: Amiens
country: France
facility: Cabinet
city: Angers
country: France
facility: Chu Angers
city: Annecy
country: France
facility: Cabinet
city: Annecy
country: France
facility: Chra Annecy
city: Armentieres
country: France
facility: Centre Hospitalier d'Armentieres
city: Armentieres
country: France
facility: CH Armentières
city: Bordeaux
country: France
facility: Cabinet
city: Bourgoin Jallieu
country: France
facility: Cabinet
city: Bourgoin-Jallieu
country: France
facility: Ch Bourgoin-Jallieu
city: Brest
country: France
facility: Hia Brest
city: Brest
country: France
facility: Chu Brest
city: Caen
country: France
facility: CHU
city: Carcassonne
country: France
facility: Cabinet
city: Chalon Sur Saone
country: France
facility: Cabinet
city: Chalon sur Saone
country: France
facility: Ch Chalon Sur Saone
city: Chambery
country: France
facility: CH de Chambéry
city: Clapiers
country: France
facility: Cabinet
city: Clermont-Ferrand
country: France
facility: Chu Clermont-Ferrand
city: Clermont-ferrand
country: France
facility: CHU Gabriel Montpied
city: Dijon
country: France
facility: Cabinet
city: Dijon
country: France
facility: Hôpital du bocage
city: Echirolles
country: France
facility: Cabinet
city: Genas
country: France
facility: Cabinet
city: Grenoble
country: France
facility: Cabinet
city: Grenoble
country: France
facility: Chu Grenoble
city: Hennebont
country: France
facility: Cabinet
city: Issy Les Moulineaux
country: France
facility: Cabinet
city: La Rochelle
country: France
facility: Ch La Rochelle
city: Lille
country: France
facility: Cabinet
city: Lille
country: France
facility: Chru Lille
city: Lomme
country: France
facility: Hopital Saint Philibert
city: Lyon
country: France
facility: CH Pierre-Bénite
city: Montbonnot St Martin
country: France
facility: Cabinet
city: Montelimar
country: France
facility: Cabinet
city: Montigny Les Metz
country: France
facility: Cabinet
city: Montlucon
country: France
facility: Cabinet
city: Montpellier
country: France
facility: Chu Montpellier
city: Mâcon
country: France
facility: CH Mâcon
city: Nantes
country: France
facility: Chu Hotel Dieu
city: Orleans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: HEGP
city: Paris
country: France
facility: Hôpital St Joseph
city: Peronne
country: France
facility: Cabinet
city: Saint-Aubin-sur-Scie
country: France
facility: Cabinet
city: Selestat
country: France
facility: Cabinet
city: St Alban
country: France
facility: Cabinet
city: St Etienne
country: France
facility: Chu St Etienne
city: Thonon Les Bains
country: France
facility: Cabinet
city: Toulouse
country: France
facility: Chu Toulouse
city: Tournefeuille
country: France
facility: Cabinet
city: Villeurbanne
country: France
facility: Cabinet
city: Vizille
country: France
facility: Cabinet
Study officials:
affiliation: CIC Grenoble
name: Jean-Luc BOSSON, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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citation: Kahn SR, Elman E, Rodger MA, Wells PS. Use of elastic compression stockings after deep venous thrombosis: a comparison of practices and perceptions of thrombosis physicians and patients. J Thromb Haemost. 2003 Mar;1(3):500-6. doi: 10.1046/j.1538-7836.2003.00098.x.
citation: Benko T, Cooke EA, McNally MA, Mollan RA. Graduated compression stockings: knee length or thigh length. Clin Orthop Relat Res. 2001 Feb;(383):197-203.
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citation: Nelson EA, Harper DR, Prescott RJ, Gibson B, Brown D, Ruckley CV. Prevention of recurrence of venous ulceration: randomized controlled trial of class 2 and class 3 elastic compression. J Vasc Surg. 2006 Oct;44(4):803-8. doi: 10.1016/j.jvs.2006.05.051.
citation: Arpaia G, Cimminiello C, Mastrogiacomo O, de Gaudenzi E. Efficacy of elastic compression stockings used early or after resolution of the edema on recanalization after deep venous thrombosis: the COM.PRE Trial. Blood Coagul Fibrinolysis. 2007 Mar;18(2):131-7. doi: 10.1097/MBC.0b013e328011f2dd.
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citation: Delluc A, Gouedard C, De Saint Martin L, Garcia C, Roguedas AM, Bressollette L, Misery L, Mottier D, Le Gal G. [Incidence, risk factors and skin manifestations of post-thrombotic syndrome: a four-year follow-up of patients included in the EDITH study]. Rev Med Interne. 2010 Nov;31(11):729-34. doi: 10.1016/j.revmed.2010.07.018. Epub 2010 Sep 29. French.