Clinical trial NCT00740987: Efficacy of the Association Mechanical Prophylaxis + Anticoagulant Prophylaxis on Venous Thromboembolism Incidence in Intensive Care Unit (ICU)
Official title: Evaluation of Intermittent Pneumatic Compression Associated With Elastic Stockings and Anticoagulant Prophylaxis Versus Anticoagulant Prophylaxis Alone on Venous Thromboembolism Incidence in ICU Patients Without High Risk of Bleeding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: No High Risk of Hemorrhage
Keywords: Mechanical device
Intermittent pneumatic compression
Venous thromboembolism prophylaxis
Intensive care unit
Hospitalization
Intensive
Care
Unit
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
Collaborators: name: Tyco Healthcare Group
First posted: 2008-08-25
Enrollment: 621
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: This multicentre open-label randomized parallel-group trial aims to compare the association of intermittent pneumatic compression of the lower limbs + elastic stockings + anticoagulant prophylaxis to anticoagulant prophylaxis alone on the incidence of venous thromboembolism systematically evaluated at day 6, in patients hospitalized in intensive care units and without high bleeding risk.

Detailed description: Background: Venous thromboembolism is a leading cause of morbi-mortality for patients hospitalized in intensive medical care units. Nevertheless, few studies evaluating prophylactic methods exist. Data from these studies demonstrate however that unfractionated heparin and low molecular weight heparin are effective to reduce the incident rate of asymptomatic deep venous thrombosis (DVT) of the lower limbs by 50 % compared to the absence of prophylaxis. Rate of asymptomatic DVT remains about 15 %. Mechanical devices such as elastic stockings (ES) or intermittent pneumatic compression (IPC), devoid of bleeding risk, can be associated with heparins, with good efficacy in some specific clinical settings. The effect of combined treatment use has never been evaluated rigorously in intensive medical care units.

Objective:

To compare the association IPC+ ES + anticoagulant prophylaxis to anticoagulant prophylaxis alone in patients without high bleeding risk and hospitalized in medical intensive care units on symptomatic or asymptomatic venous thromboembolism incidence, evaluated systematically at day 6.

Design: Multicentre open-label randomized parallel-group trial with blinded evaluation of outcomes, and an inclusion period of 24 month. Brest CIC (Centre d'Investigations cliniques, research center) coordinates this multicentre trial.

Outcomes:

The primary endpoint is a combined criterion (blindly evaluated) between day 1 and day 6:

1) Non fatal symptomatic venous thromboembolic event (objectively confirmed) between day 1 and day 6, 2) death due to a pulmonary embolism between day 1 and day 6, and 3) asymptomatic DVT detected by ultrasonography systematically done at day 6.

Patients number:

Assuming a DVT frequency of 10 % in the control group (anticoagulant prophylaxis alone), we calculated that 1436 patients will be required for the study to have 80% power to detect a 40 % reduction in the relative risk with a two-sided alpha level of 5%. Because of about 20 % deaths in the first days, we decide to increase the number at 1580 subjects.

Statistical analysis:

Efficacy analysis is performed on an 'intention-to-treat' basis. The frequencies of the combined primary outcome at day 6 are compared between groups using an exact one-sided Fischer test. Adjustment for stratification variables used Cochran-Mantel-Haenszel test. Relative risk and absolute risk reduction are computed with their 95% CIs. A logistic regression model is used to take into account potential imbalance in baseline characteristics.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 Years,
* Admission in intensive medical care unit
* No high risk for hemorrhage in CIREA 2
* Written informed consent given by the patient or relative.

High risk for hemorrhage is defined by:

* symptomatic bleeding or organic lesions likely to bleed,
* hemophilic diseases,
* haemostatic abnormalities: platelet count \< 50 000/mm 3, APTT \> 2 N, prothrombin time \< 40%,
* recent intra-cerebral hemorrhage,
* severe anemia (Hemoglobin \< 7 g/dl) due to a bleeding or unexplained.

Exclusion Criteria:

* Age \< 18 years,
* Patient refusal,
* Admission in intensive care unit ≥ 36 hours
* Admission in intensive care unit likely for \< 72 hours
* A "do not resuscitate" order
* IPC contra-indication: Recent DVT (\< 3 month), severe lower limbs arteriopathy (III and IV), any arterial graft of the legs, a wound in the lower limb related either to a vascular disease (ulcer) or a trauma.
* High risk for hemorrhage
* Patient who needs a curative anticoagulant treatment (DVT, PE, PE suspicion, atrial fibrillation, myocardial infarction, acute coronary syndrome...).
* Patients with anticoagulant prophylaxis contra-indication

Primary outcomes:
measure: combined criterion evaluated at day 6 ± 2 days after randomization: symptomatic venous thromboembolic event, non fatal, objectively confirmed, Death related to PE, Asymptomatic DVT of the lower limbs detected by CUS on day 6.
timeFrame: 6 +/- 2 days
Secondary outcomes:
measure: Symptomatic thromboembolic events occurred between day 6 and day 90, and total mortality evaluated at 1 month and 3 months.
timeFrame: 6 days to 3 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Angoulême
country: France
facility: CH d'Angoulême
city: Brest
country: France
facility: HIA Clermont-Tonnerre
city: Brest
country: France
facility: Medical Intensive Care Unit
city: Corbeil Essonne
country: France
facility: CH de Corbeil Essonne
city: Dijon
country: France
facility: CHU de Dijon
city: Lille
country: France
facility: Medical Intensive Care Unit
city: Montauban
country: France
facility: CH Montauban
city: Morlaix
country: France
facility: CH de Morlaix
city: Paris
country: France
facility: Medical Intensive Care Unit
city: Poitiers
country: France
facility: CHU de Poitiers
city: Quimper
country: France
facility: CH de Quimper
city: Saint Malo
country: France
facility: CH de St Malo
city: Tours
country: France
facility: CHU de Tours
city: Monaco
country: Monaco
facility: CH Monaco
Study officials:
affiliation: CHU Brest France, Univ Brest, EA 3878
name: Karine LACUT, MD
role: STUDY_DIRECTOR
References: