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Trial record 48 of 56 for:    "Lung Disease" | "Dalteparin"

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

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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:
Information provided by (Responsible Party):
Scripps Health

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Prevention
Conditions Venous Thromboembolic Disease
Deep Vein Thrombosis
Pulmonary Embolism
Interventions Drug: 5000 Units unfractionated Heparin Q 8 hr
Drug: 30mg enoxaparin Q12 hr
Enrollment 495
Recruitment Details From November 15, 2012 through September 15, 2014, consecutively admitted adult trauma patients were evaluated for eligibility for the study. Patients aged 18 years and older and at risk for Venous thromboembolic event (VTE) based on the American College of Chest Physicians guidelines were included.
Pre-assignment Details Those with an estimated Injury Severity Score (ISS) equal to or less than 9, those expected to have a hospital length of stay less than seven days by reason of discharge or death, and prisoners were excluded.
Arm/Group Title 5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Hide Arm/Group Description

Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.

5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.

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.

30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis

Period Title: Overall Study
Started 251 244
Completed 220 216
Not Completed 31 28
Reason Not Completed
Protocol Violation             31             28
Arm/Group Title 5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours Total
Hide Arm/Group Description

Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.

5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.

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.

30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis

Total of all reporting groups
Overall Number of Baseline Participants 220 216 436
Hide Baseline Analysis Population Description
Basic demographic and clinical characteristics of trauma patients who met all inclusion criteria.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 220 participants 216 participants 436 participants
46.5  (21.2) 46.4  (20.8) 46.4  (21.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 220 participants 216 participants 436 participants
Female
60
  27.3%
64
  29.6%
124
  28.4%
Male
160
  72.7%
152
  70.4%
312
  71.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 220 participants 216 participants 436 participants
220 216 436
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 220 participants 216 participants 436 participants
26.1  (4.5) 26.9  (5.2) 26.5  (4.9)
Injury Severity Score   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 220 participants 216 participants 436 participants
10
(1 to 50)
9
(1 to 38)
9
(1 to 50)
[1]
Measure Description: The Injury Severity Score (ISS) is an anatomical scoring system that provides an overall score for patients with multiple injuries. Each injury is assigned an Abbreviated Injury Scale (AIS) score allocated to one of six body regions (Head, Face, Chest, Abdomen, Extremities, External). The highest AIS scores among the three most severely injured body regions are squared and added together to produce the total ISS score. The ISS score ranges from 0 to 75. Each AIS score ranges from 1 to 6 (6 denotes an unsurvivable injury).
1.Primary Outcome
Title Lower Extremity Deep Vein Thrombosis
Hide Description 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.
Time Frame Within 30 days of hospital admission
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Hide Arm/Group Description:

Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.

5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.

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.

30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis

Overall Number of Participants Analyzed 105 103
Measure Type: Number
Unit of Measure: percentage of patients
4.8 2.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 5000 Units Unfractionated Heparin Q 8 Hours, 30mg Enoxaparin Q12 Hours
Comments Analysis was performed in a subset of patients who received at least one follow-up venous duplex ultrasound of the lower extremities.
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 10% noninferiority margin was selected based on a previous trial showing a difference in the incidence of DVT of 13% with the use of 30 mg of enoxaparin every 12 hours compared to 5,000 U of unfractionated heparin (UFH) every 12 hr. To achieve 90% power using an a priori margin of 10% with a one-sided alpha of 0.025, a total of 182 patients (91 in each arm) was required.
Statistical Test of Hypothesis P-Value 0.025
Comments One-tailed test of the cumulative VTE incidence between treatment groups.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.5
Confidence Interval (2-Sided) 95%
-2.9 to 15.8
Estimation Comments Unadjusted cumulative incidence values between the two treatment groups were subtracted to calculate the risk difference for VTE between groups. This difference was compared to the a priori 10% margin of difference using the 95% confidence interval.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 5000 Units Unfractionated Heparin Q 8 Hours, 30mg Enoxaparin Q12 Hours
Comments Analysis was performed in the total sample of eligible patients and who received their assigned treatment (referred to as the "randomized treated sample") .
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 10% noninferiority margin was selected based on these data showing a difference in the incidence of DVT of 13% with the use of 30 mg of enoxaparin every 12 hours compared to 5,000 U of UFH every 12 hours. To achieve 90% power using an a priori margin of 10% with a one-sided alpha of 0.025, a total of 182 patients (91 in each arm) was required. This analysis was performed in the entire sample.
Statistical Test of Hypothesis P-Value 0.025
Comments One-tailed test of the cumulative VTE incidence between treatment groups.
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
-1.6 to 7.7
Estimation Comments Unadjusted cumulative incidence values between the two treatment groups were subtracted to calculate the risk difference for VTE between groups. This difference was compared to the a priori 10% margin of difference using the 95% confidence interval.
2.Primary Outcome
Title Pulmonary Embolus
Hide Description 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.
Time Frame Within 30 days from admission to hospital
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Hide Arm/Group Description:

Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.

5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.

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.

30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis

Overall Number of Participants Analyzed 105 103
Measure Type: Number
Unit of Measure: participants
1 0
3.Secondary Outcome
Title Bleeding Event
Hide Description 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.
Time Frame Within 30 days of admission to hospital
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Hide Arm/Group Description:

Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.

5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.

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.

30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis

Overall Number of Participants Analyzed 105 103
Measure Type: Number
Unit of Measure: participants
2 3
4.Secondary Outcome
Title Heparin Induced Thrombocytopenia
Hide Description 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.
Time Frame Within 30 of admission to hospital
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Hide Arm/Group Description:

Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.

5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.

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.

30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis

Overall Number of Participants Analyzed 105 103
Measure Type: Number
Unit of Measure: participants
1 0
Time Frame 30 days after admission.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Hide Arm/Group Description

Low Dose Unfractionated Heparin (5000 Units) given every eight hours until primary or secondary outcome measure reached, discharge, or >30 days on trauma service.

5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.

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.

30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis

All-Cause Mortality
5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/220 (1.36%)      1/216 (0.46%)    
Blood and lymphatic system disorders     
Heparin-induced thrombocytopenia  [1]  1/220 (0.45%)  1 0/216 (0.00%)  0
Injury, poisoning and procedural complications     
Trauma-related mortality  1 [2]  2/220 (0.91%)  2 1/216 (0.46%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, In-hospital death
[1]
Same as one of the outcomes.
[2]
Trauma-related in-hospital mortality within 30 days of admission following administration of treatment.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
5000 Units Unfractionated Heparin Q 8 Hours 30mg Enoxaparin Q12 Hours
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/220 (1.36%)      5/216 (2.31%)    
Blood and lymphatic system disorders     
Bleeding events  [1]  3/220 (1.36%)  3 5/216 (2.31%)  5
Indicates events were collected by systematic assessment
[1]
Minor or Major bleeding events
The lack of long-term follow-up to identify VTE events among patients who were either transferred or readmitted to other facilities with VTE-related events was not performed. Published risk estimates were inaccurate for our sample size calculation.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Steven R. Shackford, MD
Organization: Scripps Mercy Hospital
Phone: 619-299-2600
EMail: shackford.steven@scrippshealth.org
Layout table for additonal information
Responsible Party: Scripps Health
ClinicalTrials.gov Identifier: NCT01729559     History of Changes
Other Study ID Numbers: IRB-12-5973
First Submitted: November 14, 2012
First Posted: November 20, 2012
Results First Submitted: July 29, 2015
Results First Posted: July 18, 2016
Last Update Posted: July 18, 2016