Thrombelastography Based Dosing of Enoxaparin

Thrombelastography Based Dosing of Enoxaparin for Thromboprophylaxis: a Prospective Randomized Trial

The risk of developing a blood clot occurs in up to 60% of all critical care patients. Many times enoxaparin (or Lovenox®) is given to patients who are at a higher risk of developing clots in their legs or lungs. Recent data suggest that a standard dose of Lovenox may not fully prevent the development of these clots especially in critically ill or obese patients. Routine enoxaparin dosing can also result in bleeding complications. Thrombelastography (TEG®) can be used to measure how blood clots. The purposes of this study are:

• to learn if the TEG® can better guide physicians in prescribing an effective dose of Lovenox compared to standard doses recommended by the drug company in preventing blood clots from developing in the legs and lungs, and
• to compare the development of blood clots in patients receiving the standard dose of enoxaparin compared to patients receiving a TEG® guided dose of enoxaparin.
• to determine if TEG guided dosing results in decreased bleeding complications compared to standard dosing.

Study Overview

• Status: Completed
• Conditions: Thromboembolic Complications
• Intervention / Treatment: Drug: Enoxaparin 30 mg BID; Drug: Enoxaparin dose adjusted Lovenox based on TEG

Detailed Description

Hypothesis:

Enoxaparin dosed to maintain a TEG® ΔR greater than 1.0 minute will decrease the incidence of DVT compared to standard dosing.

Initiation of enoxaparin thromboprophylaxis will be done by the treatment team. Once enrolled, the subject will be randomized to continue receiving standard dose enoxaparin (30 mg twice daily) or variable TEG® guided enoxaparin dosing. The treatment team and the subject will be blinded regarding the arm in which the patient is enrolled. Patient characteristics: age, gender, body mass index (BMI), comorbidities, Acute Physiology and Chronic Health Evaluation II score (APACHE II), injuries, and operations will be collected. As part of standard protocol in the ICU, all patients will undergo weekly ultrasound duplex examination of the lower extremities for presence of deep venous thrombosis.

A baseline TEG® will be completed on each patient when they are enrolled in the study. The blood will be drawn between four and six hours after the morning dose is administered, corresponding to maximum tissue levels of enoxaparin. TEG® assays will be run in duplicate for each patient, with and without heparinase, which negates the effects of enoxaparin in the assay.

Those patients randomized to the control arm of the study will have TEG® performed at baseline and daily for one week, then twice weekly. The twice weekly TEG® assays will be done until the patient is discharged from inpatient care or enoxaparin is discontinued by the treatment team. No adjustments will be made to their enoxaparin dosing.

Patients in the TEG® guided enoxaparin dosing arm will start treatment as ordered by the primary treatment team. After the second TEG®, the dose of enoxaparin will be adjusted in 10 mg increments per dose in order to reach a target ΔR between 1.0 and 1.4 minutes. If the initial ΔR is greater than 1.4 minutes, the dose of enoxaparin will be decreased by 10 mg increments until the target ΔR is achieved. Patients will have TEGs® performed daily and adjustment of dosing until the target ΔR is reached. Once the target ΔR is achieved, TEG® will be done twice weekly until the patient is discharged from inpatient care or enoxaparin is discontinued by the treatment team. All patients will be assessed daily by study personnel for bleeding complications. If bleeding complications occur, subjects will be withdrawn from the study. If interim analysis identifies a significant difference in bleeding complications between groups the study will be terminated.

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • Houston, Texas, United States
      • University of Texas Health Science Center at Houston
  • Washington
    • Seattle, Washington, United States
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inpatient initiated on enoxaparin thromboprophylaxis
• Age greater than 15 years

Exclusion Criteria:

• Unable to obtain consent from patient or ARR
• Presence of: intracranial hemorrhage, brain injury
• Receiving therapeutic dose enoxaparin
• Receiving other forms of anticoagulation
• Receiving non-standard dosing regimen of enoxaparin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enoxaparin 30 mg BID; standard dose enoxaparin thromboprophylaxis (30 mg twice daily)	Drug: Enoxaparin 30 mg BID; Enoxaparin dose of 30 mg twice a day without any adjustments; Other Names: enoxaparin, lovenox
Experimental: Enoxaparin dose adjusted based on TEG; enoxaparin dose modified based on TEG results	Drug: Enoxaparin dose adjusted Lovenox based on TEG; Enoxaparin doses will be adjusted (10 mg BID) based on delta-R results from TEG. Delta-R < 1.0 min - increase dose by 10 mg BID; delta-R >/= 1.0 min and 2.0 min - decrease dose by 10 mg BID.; Other Names: enoxaparin, lovenox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of Deep Vein Thrombosis (DVT)	An ultrasound duplex will be completed at least one time after randomization to determine if the subject has developed a DVT.	Through study completion, assessed up to 120 days post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Bleeding Complications	An increase in bleeding complications will be assessed daily during hospitalization	Through study completion, assessed up to 120 days post randomization

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Trauma Research Institute; Medical Research Foundation, Oregon
• Investigators: Principal Investigator: Martin Schreiber, MD FACS, Oregon Health and Science University

Publications and helpful links

General Publications

• Connelly CR, Van PY, Hart KD, Louis SG, Fair KA, Erickson AS, Rick EA, Simeon EC, Bulger EM, Arbabi S, Holcomb JB, Moore LJ, Schreiber MA. Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma and Surgical Patients: A Randomized Clinical Trial. JAMA Surg. 2016 Oct 19;151(10):e162069. doi: 10.1001/jamasurg.2016.2069. Epub 2016 Oct 19.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: September 29, 2009
• First Submitted That Met QC Criteria: October 5, 2009
• First Posted (Estimate): October 6, 2009

Study Record Updates

• Last Update Posted (Actual): April 3, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: deep vein thrombosis; superficial venous thrombosis; pulmonary embolus
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin; Enoxaparin sodium
• Other Study ID Numbers: 001-01