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

Critical Illness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00351663
• Other study ID #: einav-1-ctil
• Status: Completed
• Phase: Phase 4
• First received: July 12, 2006
• Last updated: April 19, 2016
• Start date: February 2007
• Est. completion date: September 2015

Study information

• Verified date: April 2016
• Source: Shaare Zedek Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: September 2015
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Exclusion Criteria:

1. Patients requiring full anticoagulation

2. Administration of unfractionated heparin in the 8hrs preceding study entry

3. Existing contraindication to prophylactic dose of enoxaparin.

4. Platelets < 75,000

5. Significant renal failure (creatinine clearance <30 ml/min/m2) [39]

6. BMI > 30

7. INR > 1.7

8. Any conditions precluding treatment in the opinion of the primary physician

9. Patient /surrogate refusal

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Critical Illness
• Thrombosis
• Venous Thrombosis

Intervention

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

Locations

Country	Name	City	State
Israel	Shaare Zedek Medical Center	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Shaare Zedek Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (1)

Helviz Y, Dzigivker I, Raveh-Brawer D, Hersch M, Zevin S, Einav S. Anti-Factor Xa Activity of Prophylactic Enoxaparin Regimens in Critically Ill Patients. Isr Med Assoc J. 2016 Feb;18(2):108-13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the effect of the dosing protocols of enoxaparin for critically ill patients on aFXa activity		5 days	Yes
Secondary	bleeding/thrombotic complications		7 days	Yes