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

NCT02704052 | Completed Early Phase 1 DMC

• 1 other identifier: IRB_00086103
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

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.

Conditions

Deep Venous Thrombosis; Pulmonary Embolus; Venous Thromboembolism

Outcome Measures

Primary Outcomes (1)

• Venous thromboembolism

  Symptomatic 90-day VTE confirmed with imaging

  90 days

Secondary Outcomes (1)

• Re-operative hematoma

  90 days

Study Arms (2)

Standard enoxaparin dose

ACTIVE COMPARATOR

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.

Drug: Standard enoxaparin dose

Real time enoxaparin dose adjustment

EXPERIMENTAL

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.

Drug: Real time enoxaparin dose adjustment

Interventions

Real time enoxaparin dose adjustment 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.

Real time enoxaparin dose adjustment

Standard enoxaparin dose DRUG

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

Standard enoxaparin dose

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah Hospitals

Salt Lake City, Utah, 84132, United States

Location

Related Publications (2)

• 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.

  PMID: 33086312 DERIVED

• 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.

  PMID: 31116389 DERIVED

MeSH Terms

Conditions

Venous Thrombosis; Pulmonary Embolism; Venous Thromboembolism

Condition Hierarchy (Ancestors)

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

Study Officials

• Christopher Puccini, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: March 7, 2016
• First Posted: March 9, 2016
• Study Start: March 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: October 1, 2018
• Last Updated: May 24, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)