Enoxaparin Metabolism in Reconstructive Surgery Patients

NCT02411292 | Completed Phase 2 Results DMC

• 1 other identifier: IRB 00079118
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Venous thromboembolism (VTE) is a leading cause of death among hospitalized patients, and is an important patient safety issue in plastic surgery. Previous work has shown that enoxaparin prophylaxis can prevent many post-operative VTE events, and current American Society of Plastic Surgeons guidelines support enoxaparin prophylaxis for high-risk patients. Highest risk patients often have cancer or trauma reconstruction. Primary outcomes include 1) peak and trough steady-state aFXa levels in response to standard and escalated doses of enoxaparin and 2) the proportion of patients with appropriate aFXa levels pre and post initiation of a clinical protocol for enoxaparin dose adjustment. The investigators expect that standard dosing will result in inadequate aFXa peak and trough levels, and that the clinical dose adjustment protocol will significantly improve the proportion of in-range aFXa levels. The investigators will also develop a linear regression-based equation to calculate, based on patient-level factors, the required dose of enoxaparin to generate in-range aFXa levels. This research may show that the current "one size fits all" approach to enoxaparin prophylaxis is insufficient. 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 Venous Thrombosis; Pulmonary Embolus; Reconstructive Surgery

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 0.3-0.5IUmL), 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.

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:

• adult (age ≥18) patients presenting for reconstructive surgery under general anesthesia.
• expected post-operative stay will be at least three days to allow peak aFXa levels to be drawn.
• eligible patients will include those having major reconstructive surgery.

You may not qualify if:

• contraindication to use of enoxaparin,
• intracranial bleeding/stroke,
• hematoma or bleeding disorder,
• known heparin-induced thrombocytopenia,
• creatinine clearance ≤30mL/min,
• serum creatinine \>1.6mg/dL, or epidural anesthesia.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (4)

• Paolini G, Firmani G, Sorotos M, Ninkovic M, Santanelli di Pompeo F. European guidelines on peri-operative venous thromboembolism prophylaxis: first update.: Chapter 8: Plastic surgery. Eur J Anaesthesiol. 2024 Aug 1;41(8):598-603. doi: 10.1097/EJA.0000000000001998. Epub 2024 Jul 10. No abstract available.

  PMID: 38957026 DERIVED

• 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, Agarwal J, Rockwell WB, Prazak AM, Momeni A. The Impact of Once- versus Twice-Daily Enoxaparin Prophylaxis on Risk for Venous Thromboembolism and Clinically Relevant Bleeding. Plast Reconstr Surg. 2018 Jul;142(1):239-249. doi: 10.1097/PRS.0000000000004517.

  PMID: 29649055 DERIVED

• Pannucci CJ, Fleming KI. Comparison of face-to-face interaction and the electronic medical record for venous thromboembolism risk stratification using the 2005 Caprini score. J Vasc Surg Venous Lymphat Disord. 2018 May;6(3):304-311. doi: 10.1016/j.jvsv.2017.10.016. Epub 2018 Feb 13.

  PMID: 29452956 DERIVED

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

Results Point of Contact

• Title: Dr. Christopher J. Pannucci, M.D., M.S.
• Organization: Division of Plastic Surgery, University of Utah

christopher.pannucci@hsc.utah.edu

801-581-7719

Study Officials

• Christopher Puccini, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

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: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Plastic Surgery

Study Record Dates

• First Submitted: March 30, 2015
• First Posted: April 8, 2015
• Study Start: March 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: June 1, 2016
• Last Updated: November 16, 2018
• Results First Posted: September 13, 2017

Record last verified: 2018-10

Locations

US (1)