Venous Thromboembolic DiseasePhase 4NCT01729559
Venous Thromboembolic Prophylaxis After Trauma: Three Times a Day Unfractionated Heparin Versus Twice a Day Enoxaparin
A Phase 4 study testing 5000 Units unfractionated Heparin Q 8 hr and 30mg enoxaparin Q12 hr in people with Venous Thromboembolic Disease and Deep Vein Thrombosis, run by Scripps Health at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolic Disease, Deep Vein Thrombosis, Pulmonary Embolism
- What is being tested?
- 5000 Units unfractionated Heparin Q 8 hr and 30mg enoxaparin Q12 hr
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 495 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to Oct 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admitted to Scripps Mercy Trauma Service
- ≥18 Years old
- Stratified to either Significant or Highest risk of VTE by ACCP guidelines
Who cannot join
- 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
Show all 9Show fewer
- Evidence of renal insufficiency (Cr ≥1.3)
- Delayed transfer to this facility (>24 hrs)
- Prisoners
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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:
- Assess the degree of risk for VTE in each patient admitted to the trauma service
- 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.
- Identify and quantify any adverse events associated with either treatment arm.
- Compare the value of LMWH versus LDUH in the prophylactic treatment of VTE disease in trauma patients.
- Being tested
- 5000 Units unfractionated Heparin Q 8 hr, 30mg enoxaparin Q12 hr
- Keywords
- venous thromboembolic disease, deep vein thrombosis, pulmonary embolism, trauma, antithrombotic prophylaxis
- Medical subject headings
- Venous Thrombosis, Pulmonary Embolism, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5000 Units unfractionated Heparin Q 8 hrDrug
Also called LDUH
Venous thromboembolic prophylaxis medication
30mg enoxaparin Q12 hrDrug
Also called Lovenox, LMWH, enoxaparin
Venous thromboembolic prophylaxis
| Study group | Role | What they receive |
|---|---|---|
| 5000 Units unfractionated Heparin Q 8 hr | Experimental | Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service. Receives: Drug: 5000 Units unfractionated Heparin Q 8 hr |
| 30mg enoxaparin Q12 hr | Active comparator | 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. Receives: Drug: 30mg enoxaparin Q12 hr |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Within 30 days from admission to hospital
Secondary outcomes (2)
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.
Measured: 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.
Measured: Within 30 of admission to hospital
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionSep 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Venous Thromboembolic DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 495 participants (actual)
Sponsor and investigators
- Lead sponsor
- Scripps Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven R Shackford, MD, Principal investigator, Scripps Mercy Hospital, Department of Trauma Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01729559
- Sponsor's protocol ID
- IRB-12-5973
- Status last verified
- Jun 2016
- First submitted
- 14 Nov 2012
- Last updated
- 18 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Venous Thromboembolic Prophylaxis After Major Trauma: A Randomized Controlled Trial of Three Times a Day Unfractionated Heparin Versus Twice a Day Enoxaparin
- ClinicalTrials.gov ID
- NCT01729559
- Acronym / sponsor ID
- IRB-12-5973
- Keywords
- venous thromboembolic disease, deep vein thrombosis, pulmonary embolism, trauma, antithrombotic prophylaxis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 495 participants (actual)
- Lead sponsor
- Scripps HealthUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 20 Nov 2012 (estimated)
- Results
- Posted 18 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- Assess the degree of risk for VTE in each patient admitted to the trauma service
- 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.
- Identify and quantify any adverse events associated with either treatment arm.
- Compare the value of LMWH versus LDUH in the prophylactic treatment of VTE disease in trauma patients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5000 Units unfractionated Heparin Q 8 hr | Experimental | Drug: 5000 Units unfractionated Heparin Q 8 hrLow Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service. |
| 30mg enoxaparin Q12 hr | Active comparator | Drug: 30mg enoxaparin Q12 hrRandomly 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Admitted to Scripps Mercy Trauma Service
- ≥18 Years old
- Stratified to either Significant or Highest risk of VTE by ACCP guidelines
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5000 Units unfractionated Heparin Q 8 hrAlso: LDUHVenous thromboembolic prophylaxis medication | Drug | 5000 Units unfractionated Heparin Q 8 hr |
| 30mg enoxaparin Q12 hrAlso: Lovenox, LMWH, enoxaparinVenous thromboembolic prophylaxis | Drug | 30mg enoxaparin Q12 hr |
Primary outcome
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.
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.
2 secondary outcomes
Bleeding Event
Time frame: Within 30 days of admission to hospital
Heparin Induced Thrombocytopenia
Time frame: Within 30 of admission to hospital
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven R Shackford, MD principal investigator
Scripps Mercy Hospital, Department of Trauma Surgery
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 5000 Units unfractionated Heparin Q 8 hr and 30mg enoxaparin Q12 hr in people with Venous Thromboembolic Disease and Deep Vein Thrombosis, run by Scripps Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lower Extremity Deep Vein Thrombosis (time frame: Within 30 days of hospital admission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2016.