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

Pulmonary Embolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01729559
• Other study ID #: IRB-12-5973
• Status: Completed
• Phase: Phase 4
• First received: November 14, 2012
• Last updated: May 27, 2015
• Start date: November 2012
• Est. completion date: October 2014

Study information

• Verified date: May 2015
• Source: Scripps Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 495
• Est. completion date: October 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 (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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Deep Vein Thrombosis
• Embolism
• Pulmonary Embolism
• Thromboembolism
• Thrombosis
• Venous Thromboembolic Disease
• Venous Thrombosis

Intervention

Drug:
• 5000 Units unfractionated Heparin Q 8 hours
Venous thromboembolic prophylaxis medication
• 30mg enoxaparin Q12 hours
Venous thromboembolic prophylaxis

Locations

Country	Name	City	State
United States	Scripps Mercy Hospital	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Scripps Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 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	Yes
Primary	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	Yes
Secondary	Bleeding event	Bleeding events will be classified by the Graafsma 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	Yes
Secondary	Heparin induced thrombocytopenia	The possible occurrence of HIT will be investigated when any patient (in either LMWH or LDUH study arm) has 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 ACCP guidelines.	Within 30 of admission to hospital	Yes