Weight-Based Enoxaparin Dosing and Real-Time Dose Adjustment in Orthopaedic Trauma

NCT03339349 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 102526
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The rates of Venous thromboembolism (VTE) after orthopedic surgery are as high as 40-60% without prophylactic measures. Enoxaparin, a low-molecular-weight heparin, produces an anticoagulant effect by binding antithrombin, thereby accelerating antithrombin's inactivation of coagulation factor Xa (FXa), thus decreasing the likelihood of clot formation. Despite standard dosing enoxaparin prophylaxis, VTE rates in post-operative orthopedic trauma patients remain as high as 12.2%.The investigators will examine enoxaparin pharmacokinetics and test whether a clinical protocol for real-time enoxaparin dose adjustment can favorably alter the proportion of patients with in-range anti-Factor Xa (aFXa) levels. Outcomes will include peak and trough steady-state aFXa levels in response to standard and escalated doses of enoxaparin and the incidence of venous thromboembolism and bleeding events post-surgery. In the trauma and orthopaedic populations, patients with low initial aFXa levels are significantly more likely to develop deep venous thrombosis. Thus, this study has important implications for appropriate enoxaparin dose magnitude and frequency, and may ultimately help to decrease the substantial morbidity and mortality associated with post-operative VTE.

Conditions

Venous Thromboembolism; Deep Vein Thrombosis; Pulmonary Embolus

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Venous Thromboembolism Events

  Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery

  90 days

• Number of Participants With Bleeding Events

  Bleeding events requiring alteration in the course of care within 90 days of surgery

  90 days

Study Arms (1)

Enoxaparin Metabolism

EXPERIMENTAL

Eligible patients will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.2-0.4 IU/mL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.

Drug: Enoxaparin

Interventions

Enoxaparin DRUG

Enrolled patients will receive real-time monitoring of peak and trough steady state anti-Xa levels. Out-of-range patients will receive real time dose adjustment of Enoxaparin using a clinical protocol developed with our inpatient pharmacists.

Enoxaparin Metabolism

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Receiving orthopedic trauma surgery
• Able to have enoxaparin initiated within 36 hours after procedure

You may not qualify if:

• Intracranial bleeding/stroke
• bleeding disorder
• heparin-induced thrombocytopenia
• creatinine clearance \< 30 mL/minute
• epidural catheter
• serum creatinine \> 1.6 mg/dL

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Limitations and Caveats

Our recruitment resulted in inadequate power to analyze the data. Using an alpha of 0.05 and beta of 0.9, 107 subjects were needed for effective power.

Results Point of Contact

• Title: Daniel Jones
• Organization: University of Utah

daniel.jones2@gmail.com

801-581-2121

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 13, 2017
• Study Start: November 15, 2017
• Primary Completion: June 30, 2019
• Study Completion: October 29, 2019
• Last Updated: January 31, 2024
• Results First Posted: January 31, 2024

Record last verified: 2024-01

Locations

US (1)