Twice Daily Enoxaparin Prophylaxis in Reconstructive Surgery Patients

NCT02687204 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 86052
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

Blood clots that form in the extremities (deep venous thrombosis) and lungs (pulmonary embolus) are feared complications of reconstructive surgery. One in ten patients with symptomatic pulmonary embolus will be dead in 60 minutes. Patients with deep venous thrombosis can develop the post-thrombotic syndrome, known to be a major driver of poor quality of life. These phenomena, broadly known as venous thromboembolism (VTE), have substantial downstream ramifications, and the US Surgeon General and the American Society of Plastic Surgeons (ASPS), among others, have underscored the importance of VTE prevention in surgical patients. Reconstructive surgery, most commonly performed to fix traumatic injuries or defects after cancer excision, often involves borrowing tissue from adjacent or distant areas on the body; reconstructive surgery patients can routinely have surgical injury involving 20% or more of their total body surface area. Injury and resultant inflammation are known to increase metabolism of certain drugs, including those used to prevent VTE after surgery. Enoxaparin is a blood-thinning medication that decreases likelihood of blood clot formation. Previous research has shown that reconstructive surgery patients who are given enoxaparin after surgery are less likely to develop VTE. However, despite receiving of a standard dose of enoxaparin, many patients still develop this life-threatening complication. The investigators believe that patients metabolize enoxaparin differently based on the degree of surgical injury created during reconstruction, and seek to critically examine enoxaparin metabolism in reconstructive surgery patients. The proposed research will evaluate how enoxaparin affects the blood based on standard, ASPS-recommended dosing after reconstructive surgeries; the investigators will also examine whether the extent of surgical injury alters metabolism as well. Enoxaparin effectiveness will be tracked using anti-Factor Xa (aFXa) levels. If subtherapeutic aFXa levels are observed, the study will also design, implement and test a clinical enoxaparin dose-adjustment protocol to achieve appropriate post-operative aFXa levels. Further research based on these data will examine reduction in VTE risk when aFXa-driven enoxaparin dosing is used.

Conditions

Venous Thromboembolism; Deep Venous Thrombosis; Pulmonary Embolus

Outcome Measures

Primary Outcomes (1)

• Number of patients with a 90-day VTE (either a 90-day DVT or 90-day PE)

  Outcome measure number one will be deep venous thrombosis or pulmonary embolus confirmed with imaging within 90 days of the initial surgery.

  90 days

Secondary Outcomes (1)

• Number of patients with a 90-day re-operative hematoma

  90 days

Study Arms (2)

Enoxaparin prophylaxis

ACTIVE COMPARATOR

All enrolled patients will receive twice daily enoxaparin prophylaxis. Patients with identified out of range peak anti-Xa levels will receive real time dose adjustment and will be considered as the experimental arm.

Drug: Twice daily enoxaparin prophylaxis

Real time dose adjustment

EXPERIMENTAL

Patients with identified out of range peak anti-Xa levels will receive real time enoxaparin dose adjustment

Drug: Real time dose adjustment

Interventions

Twice daily enoxaparin prophylaxis DRUG

Patients will have peak and trough steady state anti-Xa levels drawn. For patients with out of range peak levels, real time enoxaparin dose adjustment using a clinical protocol will be performed. Repeat steady state levels will be checked.

Also known as: Lovenox

Enoxaparin prophylaxis

Real time dose adjustment DRUG

Patients will have peak and trough steady state anti-Xa levels drawn. For patients with out of range peak levels, real time enoxaparin dose adjustment using a clinical protocol will be performed. Repeat steady state levels will be checked.

Also known as: Lovenox

Real time dose adjustment

Eligibility Criteria

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

You may qualify if:

• Adult patients having plastic and reconstructive surgery who are placed on twice daily enoxaparin prophylaxis after 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
• Epidural anesthesia.

Sponsors & Collaborators

• University of Utah: lead
• Agency for Healthcare Research and Quality (AHRQ): collaborator

Study Sites (1)

University of Utah Hospitals

Salt Lake City, Utah, 84132, United States

Location

Related Publications (3)

• 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, Momeni A, Prazak AM, Agarwal J, Rockwell WB. Twice-Daily Enoxaparin among Plastic Surgery Inpatients: An Examination of Pharmacodynamics, 90-Day Venous Thromboembolism, and 90-Day Bleeding. Plast Reconstr Surg. 2018 Jun;141(6):1580-1590. doi: 10.1097/PRS.0000000000004379.

  PMID: 29608533 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

Study Officials

• Christopher Pannucci, MD MS

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 3, 2016
• First Posted: February 22, 2016
• Study Start: March 1, 2016
• Primary Completion: June 23, 2017
• Study Completion: December 6, 2017
• Last Updated: October 19, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: 9/4/18
• Access Criteria: American Society of Plastic Surgeons

Locations

US (1)