The Effect of Vasopressors on the Anti Xa Response to Enoxaparin in Critically Ill Patients

Sponsor

Shaare Zedek Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00351663

Collaborator

(none)

Enrollment

Location

Arms

103

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of 3 different dosing regimens of enoxaparin in achieving adequate antithrombotic aFXa levels in critically ill patients.

The relationship between appearance of DVT and antithrombotic aFXa levels will also be assessed and risk factors associated with inadequate aFXa levels under standard enoxaparin dosages will be searched for.

Condition or Disease	Intervention/Treatment	Phase
Venous Thrombosis Critical Illness	Drug: Enoxaparine	Phase 4

Detailed Description

Critically ill patients are at increased risk of venous thrombosis and embolism from DVT. Low molecular weigh heparins such as enoxaparin (clexane) have more favorable pharmacokinetic/ pharmacodynamic profiles, equivalent or improved efficacy (e.g. in post trauma and orthopedic surgery patients) and fewer bleeding complications than low-dose unfractionated heparin. These medications are currently recommended for DVT prophylaxis in critically ill patients and are usually administered subcutaneously (SQ). The antithrombotic activity of LMWHs correlates with peak aFXa levels. However, the the appropriate dose and dosing interval of enoxaparin for DVT prophylaxis in critically ill surgical patients has not been established and in particular remains unknown for those patients with severe peripheral edema ans/or decreased peripheral circulation due to therapy with vasopressors. Several studies have recently demonstrated questionable efficacy of standard daily enoxaparin dosing for critically ill patients as DVT prophylaxis.

The current study will be a prospective, randomized, cohort study, conducted at the Shaare Zedek Medical Center over a period of 1 year (100 patients). All critically ill patients aged ≥18 years with a predicted requirement of mechanical ventilation for >3 days will be included. Data collection will be performed anonymously and will include patient demographics and admission details, duplex monitoring for DVT and daily recording of APACHE II scores, renal function, coagulation profile and overall dose of vasopressors.

Patients will be randomized to receive enoxaparin in accordance three DVT prophylaxis protocols- IV by weight, SQ by weight or SQ 40mg x1/day (standard). Blood samples for the evaluation of aFXa will be drawn twice daily for peak and trough activity over a period of 5 days. No further changes will be made in the standard therapy. Patient outcomes and occurrence of adverse events will be recorded. The principle outcome variable will be achievement of target peak and trough levels of aFXa during the 5 day study period.

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Prospective Randomised Study of the Effect of Vasopressors on the Anti Xa Response to Enoxaparin in Critically Ill Patients

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: IV by weight intravenous dose of 0.5 mg/kg enoxaparin once daily	Drug: Enoxaparine Patients considered eligible will be divided into 2 groups- those receiving vasopressor support and those not receiving vasopressor support at the time of inclusion. The patients in each group will be randomized to receive enoxaparin in accordance with one of the following DVT prophylaxis protocols: Intravenous Enoxaparine according to their weight (0.5mg/kg x 1/day) Subcutaneous Enoxaparine according to their weight (0.5mg/kg x 1/day) Subcutaneous Enoxaparine 40mg x1/day
Active Comparator: SC fixed dose subcutaneous fixed dose of 40 mg enoxaparin once daily	Drug: Enoxaparine Patients considered eligible will be divided into 2 groups- those receiving vasopressor support and those not receiving vasopressor support at the time of inclusion. The patients in each group will be randomized to receive enoxaparin in accordance with one of the following DVT prophylaxis protocols: Intravenous Enoxaparine according to their weight (0.5mg/kg x 1/day) Subcutaneous Enoxaparine according to their weight (0.5mg/kg x 1/day) Subcutaneous Enoxaparine 40mg x1/day
Active Comparator: SC by weight subcutaneous dose of 0.5 mg/kg enoxaparin once daily	Drug: Enoxaparine Patients considered eligible will be divided into 2 groups- those receiving vasopressor support and those not receiving vasopressor support at the time of inclusion. The patients in each group will be randomized to receive enoxaparin in accordance with one of the following DVT prophylaxis protocols: Intravenous Enoxaparine according to their weight (0.5mg/kg x 1/day) Subcutaneous Enoxaparine according to their weight (0.5mg/kg x 1/day) Subcutaneous Enoxaparine 40mg x1/day

Arm

Intervention/Treatment

Active Comparator: IV by weight

intravenous dose of 0.5 mg/kg enoxaparin once daily

Drug: Enoxaparine

Patients considered eligible will be divided into 2 groups- those receiving vasopressor support and those not receiving vasopressor support at the time of inclusion. The patients in each group will be randomized to receive enoxaparin in accordance with one of the following DVT prophylaxis protocols: Intravenous Enoxaparine according to their weight (0.5mg/kg x 1/day) Subcutaneous Enoxaparine according to their weight (0.5mg/kg x 1/day) Subcutaneous Enoxaparine 40mg x1/day

Active Comparator: SC fixed dose

subcutaneous fixed dose of 40 mg enoxaparin once daily

Drug: Enoxaparine

Active Comparator: SC by weight

subcutaneous dose of 0.5 mg/kg enoxaparin once daily

Drug: Enoxaparine

Outcome Measures

Primary Outcome Measures

To determine the effect of the dosing protocols of enoxaparin for critically ill patients on aFXa activity [5 days]

Secondary Outcome Measures

bleeding/thrombotic complications [7 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All critically ill patients, aged ≥18 years, with a predicted requirement for mechanical ventilation of more than 3 days and for whom venous thromboembolic prophylaxis is indicated.