Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients

NCT ID: NCT02412982

Last Updated: 2021-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2019-01-31

Brief Summary

This is a pilot study to determine if anti-thrombin III (AT-III) serum concentrations differ between patients with normal versus subtherapeutic anti-Xa trough concentrations when placed on enoxaparin 30 mg twice daily for VTE prophylaxis. Secondarily, this study will compare two enoxaparin dosing strategies.

Detailed Description

This is a pilot study to determine if AT-III serum concentrations differ between patients with normal (>= 0.1 IU/mL) versus subtherapeutic (<0.1 IU/mL) anti-Xa trough concentrations when placed on enoxaparin 30 mg twice daily for venous thromboembolism (VTE) prophylaxis. Secondarily, this study will compare two enoxaparin dosing strategies: standard 30 mg twice daily and a dosing strategy based on trough anti-Xa values in high-risk trauma patients.

Specific aims include: 1) to compare the extent of reduced AT-III activity between patients with trough anti-Xa >= 0.1 IU/mL and < 0.1 IU/mL upon initial assay; 2) to determine the proportion of patients who reach goal anti-Xa and the time to goal anti-Xa achievement between two interventional dosing strategies: enoxaparin 40 mg every 12 hours (with consideration to increase to 50 mg every 12 hours if recheck anti-Xa is not at goal) and enoxaparin 30 mg every eight hours; 3) to compare anti-Xa enoxaparin dosing strategies based on VTE, bleeding rates, transfusion requirements, drug discontinuation rate and bioaccumulation, and 4) to determine patient-specific factors that correlate to subtherapeutic anti-Xa such as serial AT-III activity, weight, body mass index, age, cumulative fluid administration, and thromboelastography (TEG).

Conditions

Traumatic Injury; Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Serum anti-Xa >= 0.1 IU/mL

Patients with serum anti-Xa level \>= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours

Group Type: NO_INTERVENTION

No interventions assigned to this group

Anti-Xa <0.1 IU/mL:enoxaparin 40 mg q12h

Patients with serum anti-Xa level \< 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 40 mg every 12 hours. If repeat steady state trough anti-Xa is subtherapeutic, dose will be increased to enoxaparin 50 mg every 12 hours.

Group Type: ACTIVE_COMPARATOR

Enoxaparin 40 mg q12h

Intervention Type: DRUG

Patients receive enoxaparin 40 mg every 12 hours. Dose will be escalated to enoxaparin 50 mg every 12 hours if steady state trough concentration is still subtherapeutic.

Anti-Xa <0.1 IU/mL:enoxaparin 30 mg q8h

Patients with serum anti-Xa level \< 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 30 mg every eight hours

Group Type: ACTIVE_COMPARATOR

Enoxaparin 30 mg q8h

Intervention Type: DRUG

Patients receive enoxaparin 30 mg every 8 hours.

Serum anti-Xa < 0.1 IU/mL

Patients with serum anti-Xa level \< 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Enoxaparin 40 mg q12h

Patients receive enoxaparin 40 mg every 12 hours. Dose will be escalated to enoxaparin 50 mg every 12 hours if steady state trough concentration is still subtherapeutic.

Intervention Type: DRUG

Enoxaparin 30 mg q8h

Patients receive enoxaparin 30 mg every 8 hours.

Intervention Type: DRUG

Other Intervention Names

no other name; no other name

Eligibility Criteria

Inclusion Criteria

• Multi-system trauma
• Anticipated length of stay of at least 72 hours
• At high risk (risk adjustment profile [RAP] >= 5) and initiated on enoxaparin 30 mg every 12 hours per VTE prophylaxis protocol
• No counterindication to trauma team VTE prophylaxis protocol (e.g., intracranial bleeding, incomplete spinal cord injury with hematoma within 24 hours post injury, ongoing hemorrhage, uncorrected coagulopathy, >= grade IV liver or spleen injury, intraocular injury)

Exclusion Criteria

• Renal dysfunction (creatinine clearance < 30 mL/min or on continuous renal replacement therapy)
• Weight < 50 kg or > 150 kg
• Platelet count < 50,000
• Allergy to heparin or low molecular weight heparin
• On therapeutic anticoagulation on admission or requiring it within 24 hours of admission
• Isolated intracranial hemorrhage
• Known hyperbilirubinemia (serum bilirubin > 6.6 mg/dL)
• Pregnancy
• Incarceration

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Air Force

FED

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Molly Droege

Clinical Pharmacy Specialist, Trauma, Surgery, and Orthopedics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Molly Droege, PharmD

Role: PRINCIPAL_INVESTIGATOR

UC Health - University of Cincinnati Medical Center

Locations

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Countries

United States

References

Droege ME, Droege CA, Philpott CD, Webb ML, Ernst NE, Athota K, Wakefield D, Dowd JR, Gomaa D, Robinson BHR, Hanseman D, Elterman J, Mueller EW. Impact of antithrombin III and enoxaparin dosage adjustment on prophylactic anti-Xa concentrations in trauma patients at high risk for venous thromboembolism: a randomized pilot trial. J Thromb Thrombolysis. 2021 Nov;52(4):1117-1128. doi: 10.1007/s11239-021-02478-4. Epub 2021 May 12.

Reference Type: RESULT

PMID: 33978907 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

Droege2015

Identifier Type: -

Identifier Source: org_study_id