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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dr Sharon Einav, Shaare Zedek Medical Center
ClinicalTrials.gov Identifier:
NCT00351663
First received: July 12, 2006
Last updated: April 19, 2016
Last verified: April 2016
  Purpose

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 Intervention Phase
Venous Thrombosis
Critical Illness
Drug: Enoxaparine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (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

Resource links provided by NLM:


Further study details as provided by Shaare Zedek Medical Center:

Primary Outcome Measures:
  • To determine the effect of the dosing protocols of enoxaparin for critically ill patients on aFXa activity [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • bleeding/thrombotic complications [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]

Enrollment: 39
Study Start Date: February 2007
Study Completion Date: September 2015
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:

  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
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:

  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
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:

  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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00351663

Locations
Israel
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
Sponsors and Collaborators
Shaare Zedek Medical Center
Investigators
Principal Investigator: Sharon Einav-Bromiker, MD Shaare Zedek Medical Center
  More Information

Publications:
Responsible Party: Dr Sharon Einav, Dr., Shaare Zedek Medical Center
ClinicalTrials.gov Identifier: NCT00351663     History of Changes
Other Study ID Numbers: einav-1-ctil 
Study First Received: July 12, 2006
Last Updated: April 19, 2016
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Shaare Zedek Medical Center:
Venous Thrombosis
Critical Illness
Blood Coagulation
Factor Xa

Additional relevant MeSH terms:
Thrombosis
Critical Illness
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Disease Attributes
Pathologic Processes
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on September 23, 2016