Trial Outcomes & Findings for Venous Thromboembolic Prophylaxis After Trauma: Three Times a Day Unfractionated Heparin Versus Twice a Day Enoxaparin (NCT NCT01729559)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

495 participants

Primary outcome timeframe

Within 30 days of hospital admission

Results posted on

2016-07-18

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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. 5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.	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. 30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis
Overall Study STARTED	251	244
Overall Study COMPLETED	220	216
Overall Study NOT COMPLETED	31	28

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 5000 Units unfractionated Heparin Q 8 hours: Venous thromboembolic prophylaxis medication. Patients were randomly assigned.	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. 30mg enoxaparin Q12 hours: Venous thromboembolic prophylaxis
Overall Study Protocol Violation	31	28

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5000 Units Unfractionated Heparin Q 8 Hours n=220 Participants 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.	30mg Enoxaparin Q12 Hours n=216 Participants 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 n=436 Participants Total of all reporting groups
Age, Continuous	46.5 years STANDARD_DEVIATION 21.2 • n=5 Participants	46.4 years STANDARD_DEVIATION 20.8 • n=7 Participants	46.4 years STANDARD_DEVIATION 21.0 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	64 Participants n=7 Participants	124 Participants n=5 Participants
Sex: Female, Male Male	160 Participants n=5 Participants	152 Participants n=7 Participants	312 Participants n=5 Participants
Region of Enrollment United States	220 participants n=5 Participants	216 participants n=7 Participants	436 participants n=5 Participants
Body Mass Index	26.1 kg/m^2 STANDARD_DEVIATION 4.5 • n=5 Participants	26.9 kg/m^2 STANDARD_DEVIATION 5.2 • n=7 Participants	26.5 kg/m^2 STANDARD_DEVIATION 4.9 • n=5 Participants
Injury Severity Score	10 units on a scale n=5 Participants	9 units on a scale n=7 Participants	9 units on a scale n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5000 Units Unfractionated Heparin Q 8 Hours n=105 Participants 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.	30mg Enoxaparin Q12 Hours n=103 Participants 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
Lower Extremity Deep Vein Thrombosis	4.8 percentage of patients	2.9 percentage of patients

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5000 Units Unfractionated Heparin Q 8 Hours n=105 Participants 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.	30mg Enoxaparin Q12 Hours n=103 Participants 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
Pulmonary Embolus	1 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5000 Units Unfractionated Heparin Q 8 Hours n=105 Participants 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.	30mg Enoxaparin Q12 Hours n=103 Participants 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
Bleeding Event	2 participants	3 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5000 Units Unfractionated Heparin Q 8 Hours n=105 Participants 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.	30mg Enoxaparin Q12 Hours n=103 Participants 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
Heparin Induced Thrombocytopenia	1 participants	0 participants

Adverse Events

5000 Units Unfractionated Heparin Q 8 Hours

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

30mg Enoxaparin Q12 Hours

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	5000 Units Unfractionated Heparin Q 8 Hours n=220 participants at risk 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.	30mg Enoxaparin Q12 Hours n=216 participants at risk 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
Blood and lymphatic system disorders Heparin-induced thrombocytopenia	0.45% 1/220 • Number of events 1 • 30 days after admission.	0.00% 0/216 • 30 days after admission.
Injury, poisoning and procedural complications Trauma-related mortality	0.91% 2/220 • Number of events 2 • 30 days after admission.	0.46% 1/216 • Number of events 1 • 30 days after admission.

Other adverse events

Other adverse events
Measure	5000 Units Unfractionated Heparin Q 8 Hours n=220 participants at risk 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.	30mg Enoxaparin Q12 Hours n=216 participants at risk 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
Blood and lymphatic system disorders Bleeding events	1.4% 3/220 • Number of events 3 • 30 days after admission.	2.3% 5/216 • Number of events 5 • 30 days after admission.

Additional Information

Steven R. Shackford, MD

Scripps Mercy Hospital

Phone: 619-299-2600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place