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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Scripps Health
Sponsor:
Information provided by (Responsible Party):
Scripps Health
ClinicalTrials.gov Identifier:
NCT01729559
First received: November 14, 2012
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Venous Thromboembolic Disease
Deep Vein Thrombosis
Pulmonary Embolism
Drug: 5000 Units unfractionated Heparin Q 8 hours
Drug: 30mg enoxaparin Q12 hours
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (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

Resource links provided by NLM:


Further study details as provided by Scripps Health:

Primary Outcome Measures:
  • Lower extremity deep vein thrombosis [ Time Frame: Within 30 days of hospital admission ] [ Designated as safety issue: Yes ]
    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.

  • Pulmonary Embolus [ Time Frame: Within 30 days from admission to hospital ] [ Designated as safety issue: Yes ]
    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:
  • Bleeding event [ Time Frame: Within 30 days of admission to hospital ] [ Designated as safety issue: Yes ]
    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.

  • Heparin induced thrombocytopenia [ Time Frame: Within 30 of admission to hospital ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 600
Study Start Date: November 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5000 Units unfractionated Heparin Q 8 hours
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 hours
Venous thromboembolic prophylaxis medication
Other Name: LDUH
Active Comparator: 30mg enoxaparin Q12 hours
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 hours
Venous thromboembolic prophylaxis
Other Name: Lovenox, LMWH, enoxaparin

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01729559

Contacts
Contact: Steven Shackford, MD 619-299-2600 shackford.steven@scrippshealth.org
Contact: Beth Sise, MSN 619-260-7298 sise.beth@scrippshealth.org

Locations
United States, California
Scripps Mercy Hospital Recruiting
San Diego, California, United States, 92103
Contact: Beth Sise, MSN    619-260-7298    sise.beth@scrippshealth.org   
Contact: Casey Dunne, MPH    619-686-3492    dunne.casey@scrippshealth.org   
Principal Investigator: Steven Shackford, MD         
Sponsors and Collaborators
Scripps Health
Investigators
Principal Investigator: Steven R Shackford, MD Scripps Mercy Hospital, Department of Trauma Surgery
  More Information

No publications provided

Responsible Party: Scripps Health
ClinicalTrials.gov Identifier: NCT01729559     History of Changes
Other Study ID Numbers: IRB-12-5973
Study First Received: November 14, 2012
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Scripps Health:
venous thromboembolic disease
deep vein thrombosis
pulmonary embolism
trauma
antithrombotic prophylaxis

Additional relevant MeSH terms:
Embolism
Thrombosis
Pulmonary Embolism
Venous Thrombosis
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Calcium heparin
Heparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 22, 2014