Fixed Versus Weight-Based Enoxaparin Dosing in Thoracic Surgery Patients

NCT ID: NCT03251963

Last Updated: 2020-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-15
• Study Completion Date: 2019-07-27

Brief Summary

The aim of this research is to better understand how patient-level factors can be used to predict the appropriate enoxaparin dose to maximize venous thromboembolism (VTE) risk reduction and minimize bleeding.

Detailed Description

VTE encompasses deep venous thrombosis and pulmonary embolus and is the proximate cause of death in over 100,000 hospitalized patients per year 4,5. To put this in better context, VTE kills more people each year than the annual morbidity from motor vehicle crashes and breast cancer combined-and one third of these deaths are known to occur after surgical procedures 34. "Breakthrough" VTE events occur in patients despite the receipt of guideline-compliant chemical prophylaxis. These events can be frustrating for surgeons, can represent a resource and financial burden for hospital systems, and most importantly, can be life or limb threatening for patients.

Existing data from our group and others suggests that inadequate enoxaparin dosing, quantified by aFXa levels, represents a plausible explanatory mechanism for "breakthrough" VTE events that occur among thoracic surgery patients. This project will examine the pharmacodynamics of fixed dose enoxaparin (40mg/day) after VATS-this dose and frequency were the most commonly prescribed VTE chemical prophylaxis strategy in a recent survey of thoracic surgeons 35. If inadequate aFXa levels are observed with fixed enoxaparin dosing, the study will design, implement and test a weight-based dosing approach to optimize aFXa levels. The study will also examine how alteration of enoxaparin dose magnitude affects peak aFXa levels and risk for VTE and major bleeding events.

Aim 1: To evaluate peak steady-state aFXa levels in response to a fixed dose of enoxaparin prophylaxis (40mg once daily) in VATS patients.

Rationale: Over 12% of thoracic surgery patients have "breakthrough" VTE events despite receipt of fixed dose chemical prophylaxis 29. Fixed dose enoxaparin prophylaxis has been shown to be inadequate for the majority of patients in other surgical subspecialties.

Hypothesis: Peak steady state aFXa levels will be within the accepted range (0.3-0.5 IU/mL) in 40% of patients after VATS.

Aim 2: To compare the effect of fixed (40mg once daily) and weight-based (0.5mg/kg once daily) enoxaparin prophylaxis on peak steady state aFXa levels after VATS.

Rationale: Our preliminary data shows a potential association between body weight and aFXa levels in response to fixed dosing; this will be confirmed using a multi-center approach in Aim #1. Body weight may be an important predictor of appropriate enoxaparin dose.

Hypothesis: Weight-based enoxaparin prophylaxis, when compared to fixed dose prophylaxis, will increase the proportion of patients with in-range peak aFXa levels from 40% to 80%.

Aim 3: To examine rates of 90-day VTE and clinically relevant bleeding events in VATS patients who receive fixed dose vs. weight-based enoxaparin prophylaxis.

Rationale: This observational Aim will allow us to better understand VTE and bleeding rates after VATS. Since these are rare events it is impossible to power the study to detect increases or decreases in risk between the dose groups. This study does provide a way to demonstrate an unexpected, very large difference in risk.

Hypothesis: Rates of post-operative VTE and clinically relevant bleeding will be less than 2% in each group.

Conditions

Venous Thromboembolism; Deep Venous Thrombosis; Surgery

Study Design

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

Study Groups

Fixed Dose Enoxaparin

Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.

Group Type: EXPERIMENTAL

Fixed Dose Enoxaparin

Intervention Type: DRUG

Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), 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.

Variable Dose Enoxaparin

Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.

Group Type: EXPERIMENTAL

Variable Dose Enoxaparin

Intervention Type: DRUG

Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), 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.

Interventions

Fixed Dose Enoxaparin

Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), 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.

Intervention Type: DRUG

Variable Dose Enoxaparin

Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• receiving Video-Assisted Thoracoscopic Surgery
• able to have Enoxaparin initiated within 8 hours after procedure

Exclusion Criteria

• Contraindication to use of enoxaparin
• Intracranial bleeding/stroke
• Hematoma or bleeding disorder
• Heparin-induced thrombocytopenia positive
• Creatinine clearance less than or equal to 30 mL/min
• Serum creatinine greater than 1.6 mg/dL
• Epidural catheter

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

Sponsors

University of Michigan

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Christopher Pannucci

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christopher Puccini, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

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 C, Moulton L, Stringham J, Barnett S, Lin J, Varghese TK Jr. Fixed or Weight-Tiered Enoxaparin After Thoracic Surgery for Venous Thromboembolism Prevention. Ann Thorac Surg. 2020 Jun;109(6):1713-1721. doi: 10.1016/j.athoracsur.2019.12.058. Epub 2020 Feb 8.

Reference Type: DERIVED

PMID: 32045583 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

100484

Identifier Type: -

Identifier Source: org_study_id