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

No High Risk of Hemorrhage Clinical Trial

— CIREA2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00740987
• Other study ID #: CIREA2
• Status: Completed
• Phase: Phase 3
• First received: August 22, 2008
• Last updated: February 10, 2015
• Start date: October 2007
• Est. completion date: January 2015

Study information

• Verified date: December 2014
• Source: University Hospital, Brest
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 621
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• No High Risk of Hemorrhage
• Thromboembolism
• Venous Thromboembolism

Intervention

Device:
• Intermittent pneumatic compression of the lower limbs
No Intermittent pneumatic compression of the lower limbs during hospitalisation in reanimation unit

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CH d'Angoulême	Angoulême
France	HIA Clermont-Tonnerre	Brest
France	Medical Intensive Care Unit	Brest
France	CH de Corbeil Essonne	Corbeil Essonne
France	CHU de Dijon	Dijon
France	Medical Intensive Care Unit	Lille
France	CH Montauban	Montauban
France	CH de Morlaix	Morlaix
France	Medical Intensive Care Unit	Paris
France	CHU de Poitiers	Poitiers
France	CH de Quimper	Quimper
France	CH de St Malo	Saint Malo
France	CHU de Tours	Tours
Monaco	CH Monaco	Monaco

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Brest	Tyco Healthcare Group

Countries where clinical trial is conducted

France,  Monaco, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		6 +/- 2 days	No
Secondary	Symptomatic thromboembolic events occurred between day 6 and day 90, and total mortality evaluated at 1 month and 3 months.		6 days to 3 months	No