Real-time Anti-Factor Xa Measurements in Surgical Patients to Examine Enoxaparin Metabolism and Optimize Enoxaparin Dose

NCT ID: NCT02704052

Last Updated: 2019-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-10-31

Brief Summary

Venous thromboembolism (VTE) encompasses deep venous thrombosis and pulmonary embolus, and is the proximate cause of death in over 100,000 hospitalized patients per year.

This project will critically examine the pharmacokinetics of prophylactic doses of enoxaparin in surgical patients, and will evaluate how alteration of enoxaparin dose magnitude and frequency affects peak and trough aFXa levels as well as risk for re-operative hematoma. If subtherapeutic aFXa levels are observed, the study will design, implement and test a clinical protocol to optimize post-operative aFXa levels. Although not an explicit Aim, this study will also provide important preliminary data on VTE rates in surgical patients with in range and out of range aFXa levels.

Detailed Description

Venous thromboembolism (VTE) encompasses deep venous thrombosis and pulmonary embolus, and is the proximate cause of death in over 100,000 hospitalized patients per year. To put this in better context, VTE kills more people each year than the annual morbidity from motor vehicle crashes and breast cancer combined. Surgeons commonly provide enoxaparin, a low molecular weight heparin, for VTE prophylaxis. Enoxaparin's activity is quantified by anti-Factor Xa (aFXa) levels. Studies of enoxaparin metabolism in patients with traumatic injury, thermal injury, or those undergoing reconstructive surgery have shown that standard dosing can result in inadequate aFXa levels, likely from the hypermetabolic state associated with significant injury. Small studies have associated subtherapeutic aFXa levels with increased risk for life or limb-threatening VTE events. Prior work from has shown that 2-10% of highest risk surgical patients have a VTE event despite enoxaparin prophylaxis. The investigators believe that surgical patients would benefit from an individualized dosing regimen for enoxaparin prophylaxis and that individualized dosing will decrease observed rates of life or limb-threatening post-operative VTE events.

This project will critically examine the pharmacokinetics of prophylactic doses of enoxaparin in surgical patients, and will evaluate how alteration of enoxaparin dose magnitude and frequency affects peak and trough aFXa levels as well as risk for re-operative hematoma. If subtherapeutic aFXa levels are observed, the study will design, implement and test a clinical protocol to optimize post-operative aFXa levels. Although not an explicit Aim, this study will also provide important preliminary data on VTE rates in surgical patients with in range and out of range aFXa levels.

Conditions

Deep Venous Thrombosis; Pulmonary Embolus; Venous Thromboembolism

Study Design

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

Study Groups

Standard enoxaparin dose

We will identify a convenience sample of surgical patients placed on enoxaparin prophylaxis at their attending surgeon's discretion-the proposed research will not dictate the initial enoxaparin dose magnitude or frequency. However, we will identify patients already on enoxaparin, evaluate peak and trough steady state aFXa levels, and adjust patient's dose if necessary based on steady state aFXa levels. Eligible patients will have enoxaparin prophylaxis started within 36 after surgery at their surgeon's discretion. Steady state peak and trough aFXa levels will be drawn at 4 and 12 hours, respectively, after the third enoxaparin dose. Goal peak aFXa levels will be 0.2-0.4 IU/mL for twice daily dosing and 0.3-0.5 IU/mL for once daily dosing.

Group Type: ACTIVE_COMPARATOR

Standard enoxaparin dose

Intervention Type: DRUG

Patients will be placed on enoxaparin prophylaxis per their surgeon's discretion.

Real time enoxaparin dose adjustment

Patients with identified out of range levels will receive pharmacist-driven real time enoxaparin dose adjustment and will receive followup steady state peak and trough aFXa levels. aFXa monitoring will be discontinued when in range peak levels are obtained, when enoxaparin prophylaxis is discontinued at surgeon discretion, or when the patient is discharged. Patients may be continued on enoxaparin prophylaxis after discharge per attending surgeon discretion but aFXa levels will not be followed in the outpatient environment.

Group Type: EXPERIMENTAL

Real time enoxaparin dose adjustment

Intervention Type: DRUG

Patients will have steady state peak and trough anti-Xa levels drawn after their third enoxaparin dose. Patients with out of range peak anti-Xa levels will receive real time enoxaparin dose adjustment followed by repeat peak and trough anti-Xa levels.

Interventions

Real time enoxaparin dose adjustment

Patients will have steady state peak and trough anti-Xa levels drawn after their third enoxaparin dose. Patients with out of range peak anti-Xa levels will receive real time enoxaparin dose adjustment followed by repeat peak and trough anti-Xa levels.

Intervention Type: DRUG

Standard enoxaparin dose

Patients will be placed on enoxaparin prophylaxis per their surgeon's discretion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults, (age≥18)
• Patients who have had surgery with general anesthesia.
• Post-operative stay will be ≥2 days

Exclusion Criteria

• Contradiction to use enoxaparin
• History of intracranial bleeding/stroke, hematoma or bleeding disorder, heparin-induced thrombocytopenia positive, and heparin-induced thrombocytopenia positive
• Creatinine clearance ≤ 30mL/min
• Serum creatinine >1.6mg/dL
• Epidural anesthesia
• Patients placed on non-enoxaparin chemoprophylaxis regimens per their surgeon's discretion.

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

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Christopher Pannucci

M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christopher Puccini, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah Hospitals

Salt Lake City, Utah, United States

Countries

United States

References

Pannucci CJ, Fleming KI, Varghese TK Jr, Stringham J, Huang LC, Pickron TB, Prazak AM, Bertolaccini C, Momeni A. Low Anti-Factor Xa Level Predicts 90-Day Symptomatic Venous Thromboembolism in Surgical Patients Receiving Enoxaparin Prophylaxis: A Pooled Analysis of Eight Clinical Trials. Ann Surg. 2022 Dec 1;276(6):e682-e690. doi: 10.1097/SLA.0000000000004589. Epub 2020 Oct 19.

Reference Type: DERIVED

PMID: 33086312 (View on PubMed)

Pannucci CJ, Fleming KI, Bertolaccini CB, Prazak AM, Huang LC, Pickron TB. Assessment of Anti-Factor Xa Levels of Patients Undergoing Colorectal Surgery Given Once-Daily Enoxaparin Prophylaxis: A Clinical Study Examining Enoxaparin Pharmacokinetics. JAMA Surg. 2019 Aug 1;154(8):697-704. doi: 10.1001/jamasurg.2019.1165.

Reference Type: DERIVED

PMID: 31116389 (View on PubMed)

Other Identifiers

IRB_00086103

Identifier Type: -

Identifier Source: org_study_id