Venous Thromboembolic Prophylaxis After Trauma: Three Times a Day Unfractionated Heparin Versus Twice a Day Enoxaparin

Venous Thromboembolic Prophylaxis After Major Trauma: A Randomized Controlled Trial of Three Times a Day Unfractionated Heparin Versus Twice a Day Enoxaparin

The rate of venous thromboembolic events in trauma patients at high risk for deep vein thrombosis and pulmonary embolism receiving low dose unfractionated heparin every 8 hours will be equivalent or less than a similar group of patients given a standard every 12 hour dose of low molecular weight heparin.

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis; Pulmonary Embolism; Venous Thromboembolic Disease
• Intervention / Treatment: Drug: 5000 Units unfractionated Heparin Q 8 hr; Drug: 30mg enoxaparin Q12 hr

Detailed Description

Venous thromboembolism (VTE) is a common and potentially life threatening complication of major trauma. The risk of developing deep vein thrombosis (DVT) following major trauma exceeds 50% unless adequate chemoprophylaxis is used. Recent national quality improvement initiatives, such as the Surgical Care Improvement Project (SCIP), mandate the risk stratification of hospitalized patients and the use of VTE prophylaxis based on the risk assessment. Low Molecular Weight Heparin (LMWH, enoxaparin) and Low Dose Unfractionated Heparin (LDUH) are commonly used alternatives for VTE chemoprophylaxis following major trauma. LMWH became favored in most trauma centers following a prospective randomized controlled trial comparing the two agents that demonstrated superior efficacy and equivalent safety of LMWH over a twice per day dosing of LDUH. The results of this study were largely responsible for practice guideline recommendation changes favoring the use of LMWH in trauma patients by both the American College of Chest Physicians (ACCP) and the Eastern Association for the Surgery of Trauma (EAST). , This landmark paper did not, however, utilize a three times a day (every 8 hours) dosing of LDUH for prophylaxis, which is the dosing schedule recommended by earlier trials. LDUH administered every 8 hours was demonstrated to have similar efficacy to LMWH in trauma patients in a recent retrospective study. These results call into question the validity of the conclusions of the 1996 study. Because LDUH is less expensive ($0.50/dose) than LMWH (Enoxaparin, $28/dose), similar effectiveness would imply a significant reduction in the cost of prophylaxis and increased value to patients, providers and accountable care organizations and tax-payers.

To validate this hypothesis the investigators propose to achieve the following study objectives:

1. Assess the degree of risk for VTE in each patient admitted to the trauma service

2. Determine the rate of VTE events in high risk trauma patients receiving either:

   • LMWH (30mg enoxaparin) given every twelve hours
   • LDUH (5000 Units unfractionated Heparin) given every eight hours.
3. Identify and quantify any adverse events associated with either treatment arm.
4. Compare the value of LMWH versus LDUH in the prophylactic treatment of VTE disease in trauma patients.

• Study Type: Interventional
• Enrollment (Actual): 495
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Scripps Mercy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admitted to Scripps Mercy Trauma Service
• ≥18 Years old
• Stratified to either Significant or Highest risk of VTE by ACCP guidelines

Exclusion Criteria:

• Estimated Injury Severity Score (ISS) ≤9
• Likely to be discharged before hospital day 7
• Systemic coagulopathy defined with an International Normalized Ratio (INR) of ≥1.2
• Body Mass Index (BMI) >40
• Likely to Survive for <7 Days
• Pregnancy
• Evidence of renal insufficiency (Cr ≥1.3)
• Delayed transfer to this facility (>24 hrs)
• Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5000 Units unfractionated Heparin Q 8 hr; Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.	Drug: 5000 Units unfractionated Heparin Q 8 hr; Venous thromboembolic prophylaxis medication; Other Names: LDUH
Active Comparator: 30mg enoxaparin Q12 hr; Randomly assigned trauma patients to receive Low Molecular Weight Heparin (30mg enoxaparin) given subcutaneously every twelve hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.	Drug: 30mg enoxaparin Q12 hr; Venous thromboembolic prophylaxis; Other Names: Lovenox, LMWH, enoxaparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lower Extremity Deep Vein Thrombosis	Patients will have a bilateral lower extremity duplex ultrasound performed by a registered vascular technologist twice per week if the patient is in the ICU, or once per week if the patient is on the trauma ward. All of the deep veins from the external iliac to and including the calf veins will be interrogated. Diagnosis of deep vein thrombosis (DVT) will be defined as absence of complete vein compressibility, presence of an echogenic thrombus within the vein, absence of color flow characteristics including lack of spontaneity, phasicity, pulsatility and augmentability as noted in the clinical practice guidelines of the American Thoracic Society. The vascular technologist and physician reading the ultrasound study will be blinded to the patient's enrollment status and randomization arm/medication group.	Within 30 days of hospital admission
Pulmonary Embolus	Patients with any or all of the following signs and symptoms suggestive of pulmonary embolism will have a CT angiogram (CTA) performed for diagnosis: Sudden onset of dyspnea, deterioration of existing dyspnea, decreased oxygen saturation (<92%), onset of pleuritic chest pain without another apparent cause, onset of tachycardia (>100), evidence of hypoxemia, hypocapnia, or respiratory alkalosis on arterial blood gas, or electrocardiographic changes reflecting right ventricular strain.	Within 30 days from admission to hospital

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding Event	Bleeding events will be classified by the Graafsma et al. severity of bleeding criteria (Major, Minor or No Bleeding). A major bleeding event will be defined as any overt bleeding following initiation of chemoprophylaxis associated with one or more of the following; a decrease in hemoglobin of ≥2 g/dL, bleeding leading to a transfusion of ≥2 units of packed red blood cells, a new retroperitoneal or intracranial bleed, or bleeding that warranted cessation of chemoprophylaxis treatment. Minor bleeding is defined as clinically evident bleeding not meeting criteria for major bleeding.	Within 30 days of admission to hospital
Heparin Induced Thrombocytopenia	The possible occurrence of heparin induced thrombocytopenia (HIT) was investigated when any patient (in either low molecular weight heparin [LMWH] or low dose unfractionated heparin [LDUH] study arm) had a platelet count drop of ≥50% (from a baseline value at the time of initiation of VTE prophylaxis) between day 5 and 14 following initiation of chemoprophylaxis per American College of Chest Physicians (ACCP) guidelines.	Within 30 of admission to hospital

Collaborators and Investigators

• Sponsor: Scripps Health
• Investigators: Principal Investigator: Steven R Shackford, MD, Scripps Mercy Hospital, Department of Trauma Surgery

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: November 14, 2012
• First Submitted That Met QC Criteria: November 19, 2012
• First Posted (Estimate): November 20, 2012

Study Record Updates

• Last Update Posted (Estimate): July 18, 2016
• Last Update Submitted That Met QC Criteria: June 7, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: trauma; deep vein thrombosis; pulmonary embolism; venous thromboembolic disease; antithrombotic prophylaxis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Thromboembolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Enoxaparin; Calcium heparin; Enoxaparin sodium
• Other Study ID Numbers: IRB-12-5973

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided