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

• ClinicalTrials.gov Identifier: NCT01729559
• Recruitment Status: Completed
• First Posted: November 20, 2012
• Results First Posted: July 18, 2016
• Last Update Posted: July 18, 2016
• Sponsor: Scripps Health
• Information provided by (Responsible Party): Scripps Health

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolic Disease; Deep Vein Thrombosis; Pulmonary Embolism	Drug: 5000 Units unfractionated Heparin Q 8 hr; Drug: 30mg enoxaparin Q12 hr	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 495 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Venous Thromboembolic Prophylaxis After Major Trauma: A Randomized Controlled Trial of Three Times a Day Unfractionated Heparin Versus Twice a Day Enoxaparin
• Study Start Date: November 2012
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

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 Name: 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 Name: Lovenox, LMWH, enoxaparin

Outcome Measures

Primary Outcome Measures :

1. Lower Extremity Deep Vein Thrombosis [ Time Frame: Within 30 days of hospital admission ]
   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.
2. Pulmonary Embolus [ Time Frame: Within 30 days from admission to hospital ]
   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.

Secondary Outcome Measures :

1. Bleeding Event [ Time Frame: Within 30 days of admission to hospital ]
   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.
2. Heparin Induced Thrombocytopenia [ Time Frame: Within 30 of admission to hospital ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Scripps Mercy Hospital

San Diego, California, United States, 92103

Sponsors and Collaborators

Scripps Health

Investigators

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

More Information

• Responsible Party: Scripps Health
• ClinicalTrials.gov Identifier: NCT01729559
• Other Study ID Numbers: IRB-12-5973
• First Posted: November 20, 2012
• Results First Posted: July 18, 2016
• Last Update Posted: July 18, 2016
• Last Verified: June 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Scripps Health:

venous thromboembolic disease; deep vein thrombosis; pulmonary embolism; trauma; antithrombotic prophylaxis

Additional relevant MeSH terms:

Pulmonary Embolism; Thrombosis; Embolism; Venous Thrombosis; Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Heparin; Enoxaparin; Calcium heparin; Enoxaparin sodium; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action