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

NCT ID: NCT00351663

Last Updated: 2016-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2015-09-30

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.

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.

Conditions

Venous Thrombosis; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

IV by weight

intravenous dose of 0.5 mg/kg enoxaparin once daily

Group Type: ACTIVE_COMPARATOR

Enoxaparine

Intervention Type: DRUG

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:

1. Intravenous Enoxaparine according to their weight (0.5mg/kg x 1/day)

2. Subcutaneous Enoxaparine according to their weight (0.5mg/kg x 1/day)

3. Subcutaneous Enoxaparine 40mg x1/day

SC fixed dose

subcutaneous fixed dose of 40 mg enoxaparin once daily

Group Type: ACTIVE_COMPARATOR

Enoxaparine

Intervention Type: DRUG

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:

1. Intravenous Enoxaparine according to their weight (0.5mg/kg x 1/day)

2. Subcutaneous Enoxaparine according to their weight (0.5mg/kg x 1/day)

3. Subcutaneous Enoxaparine 40mg x1/day

SC by weight

subcutaneous dose of 0.5 mg/kg enoxaparin once daily

Group Type: ACTIVE_COMPARATOR

Enoxaparine

Intervention Type: DRUG

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:

1. Intravenous Enoxaparine according to their weight (0.5mg/kg x 1/day)

2. Subcutaneous Enoxaparine according to their weight (0.5mg/kg x 1/day)

3. Subcutaneous Enoxaparine 40mg x1/day

Interventions

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:

1. Intravenous Enoxaparine according to their weight (0.5mg/kg x 1/day)

2. Subcutaneous Enoxaparine according to their weight (0.5mg/kg x 1/day)

3. Subcutaneous Enoxaparine 40mg x1/day

Intervention Type: DRUG

Eligibility Criteria

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

-

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shaare Zedek Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Dr Sharon Einav

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sharon Einav-Bromiker, MD

Role: PRINCIPAL_INVESTIGATOR

Shaare Zedek Medical Center

Locations

Shaare Zedek Medical Center

Jerusalem, , Israel

Countries

Israel

References

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.

Reference Type: RESULT

PMID: 26979004 (View on PubMed)

Other Identifiers

einav-1-ctil

Identifier Type: -

Identifier Source: org_study_id