Clinical trial NCT02704052: Real-time Anti-Factor Xa Measurements in Surgical Patients to Examine Enoxaparin Metabolism and Optimize Enoxaparin Dose
Official title: Real-time Anti-Factor Xa Measurements in Surgical Patients to Examine Enoxaparin Metabolism and Optimize Enoxaparin Dose
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Deep Venous Thrombosis
Pulmonary Embolus
Venous Thromboembolism
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2016-03-09
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Venous thromboembolism
timeFrame: 90 days
Secondary outcomes:
measure: Re-operative hematoma
timeFrame: 90 days
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah Hospitals
state: Utah
Study officials:
affiliation: University of Utah
name: Christopher Puccini, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.