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Efficacy of the Association Mechanical Prophylaxis + Anticoagulant Prophylaxis on Venous Thromboembolism Incidence in Intensive Care Unit (ICU) (CIREA2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00740987
Recruitment Status : Completed
First Posted : August 25, 2008
Last Update Posted : February 11, 2015
Tyco Healthcare Group
Information provided by (Responsible Party):
University Hospital, Brest

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.

Condition or disease Intervention/treatment Phase
No High Risk of Hemorrhage Device: Intermittent pneumatic compression of the lower limbs Phase 3

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.


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.


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 621 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2007
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
No Intervention: 1
No Intermittent pneumatic compression of the lower limbs during hospitalisation in reanimation unit
Experimental: 2
Intermittent pneumatic compression of the lower limbs during hospitalisation in reanimation unit
Device: Intermittent pneumatic compression of the lower limbs
No Intermittent pneumatic compression of the lower limbs during hospitalisation in reanimation unit

Primary Outcome Measures :
  1. 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. [ Time Frame: 6 +/- 2 days ]

Secondary Outcome Measures :
  1. Symptomatic thromboembolic events occurred between day 6 and day 90, and total mortality evaluated at 1 month and 3 months. [ Time Frame: 6 days to 3 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00740987

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CHU d'Angers
Angers, France, 49000
CH d'Angoulême
Angoulême, France, 16000
HIA Clermont-Tonnerre
Brest, France, 29 200
Medical Intensive Care Unit
Brest, France
CH de Corbeil Essonne
Corbeil Essonne, France, 91100
CHU de Dijon
Dijon, France, 21000
Medical Intensive Care Unit
Lille, France
CH Montauban
Montauban, France, 82013
CH de Morlaix
Morlaix, France, 29672
Medical Intensive Care Unit
Paris, France
CHU de Poitiers
Poitiers, France, 86000
CH de Quimper
Quimper, France, 29000
CH de St Malo
Saint Malo, France, 35403
CHU de Tours
Tours, France, 37000
CH Monaco
Monaco, Monaco
Sponsors and Collaborators
University Hospital, Brest
Tyco Healthcare Group
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Study Director: Karine LACUT, MD CHU Brest France, Univ Brest, EA 3878
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Responsible Party: University Hospital, Brest Identifier: NCT00740987    
Other Study ID Numbers: CIREA2
First Posted: August 25, 2008    Key Record Dates
Last Update Posted: February 11, 2015
Last Verified: December 2014
Keywords provided by University Hospital, Brest:
Mechanical device
Intermittent pneumatic compression
Venous thromboembolism prophylaxis
Intensive care unit
Additional relevant MeSH terms:
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Venous Thromboembolism
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases