Clinical trial NCT00351663: The Effect of Vasopressors on the Anti Xa Response to Enoxaparin in Critically Ill Patients
Official title: Prospective Randomised Study of the Effect of Vasopressors on the Anti Xa Response to Enoxaparin in Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Venous Thrombosis
Critical Illness
Keywords: Venous Thrombosis
Critical Illness
Blood Coagulation
Factor Xa
Lead sponsor: Shaare Zedek Medical Center
Sponsor class: OTHER
First posted: 2006-07-13
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

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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

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Primary outcomes:
measure: To determine the effect of the dosing protocols of enoxaparin for critically ill patients on aFXa activity
timeFrame: 5 days
Secondary outcomes:
measure: bleeding/thrombotic complications
timeFrame: 7 days
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
Study officials:
affiliation: Shaare Zedek Medical Center
name: Sharon Einav-Bromiker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.