Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients

• Sponsor: University of Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT02412982
• Collaborator: United States Air Force (U.S. Fed)
• Enrollment: 103
• Location: 1
• Arms: 4
• Duration (Months): 34
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

This is a pilot study to determine if anti-thrombin III (AT-III) serum concentrations differ between patients with normal versus subtherapeutic anti-Xa trough concentrations when placed on enoxaparin 30 mg twice daily for VTE prophylaxis. Secondarily, this study will compare two enoxaparin dosing strategies.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Injury; Venous Thromboembolism	Drug: Enoxaparin 40 mg q12h; Drug: Enoxaparin 30 mg q8h	Phase 4

Detailed Description

This is a pilot study to determine if AT-III serum concentrations differ between patients with normal (>= 0.1 IU/mL) versus subtherapeutic (<0.1 IU/mL) anti-Xa trough concentrations when placed on enoxaparin 30 mg twice daily for venous thromboembolism (VTE) prophylaxis. Secondarily, this study will compare two enoxaparin dosing strategies: standard 30 mg twice daily and a dosing strategy based on trough anti-Xa values in high-risk trauma patients.

Specific aims include: 1) to compare the extent of reduced AT-III activity between patients with trough anti-Xa >= 0.1 IU/mL and < 0.1 IU/mL upon initial assay; 2) to determine the proportion of patients who reach goal anti-Xa and the time to goal anti-Xa achievement between two interventional dosing strategies: enoxaparin 40 mg every 12 hours (with consideration to increase to 50 mg every 12 hours if recheck anti-Xa is not at goal) and enoxaparin 30 mg every eight hours; 3) to compare anti-Xa enoxaparin dosing strategies based on VTE, bleeding rates, transfusion requirements, drug discontinuation rate and bioaccumulation, and 4) to determine patient-specific factors that correlate to subtherapeutic anti-Xa such as serial AT-III activity, weight, body mass index, age, cumulative fluid administration, and thromboelastography (TEG).

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients: A Prospective Randomized Trial of Standard Enoxaparin Versus Two Anti-Xa Adjusted Dosing Strategies
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Jan 1, 2019
• Actual Study Completion Date: Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Serum anti-Xa >= 0.1 IU/mL Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours
Active Comparator: Anti-Xa <0.1 IU/mL:enoxaparin 40 mg q12h Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 40 mg every 12 hours. If repeat steady state trough anti-Xa is subtherapeutic, dose will be increased to enoxaparin 50 mg every 12 hours.	Drug: Enoxaparin 40 mg q12h; Patients receive enoxaparin 40 mg every 12 hours. Dose will be escalated to enoxaparin 50 mg every 12 hours if steady state trough concentration is still subtherapeutic.; Other Names: no other name
Active Comparator: Anti-Xa <0.1 IU/mL:enoxaparin 30 mg q8h Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours who then receive enoxaparin 30 mg every eight hours	Drug: Enoxaparin 30 mg q8h; Patients receive enoxaparin 30 mg every 8 hours.; Other Names: no other name
No Intervention: Serum anti-Xa < 0.1 IU/mL Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours

Outcome Measures

Primary Outcome Measures

1. Initial AT-III Activity -- Control Group vs. Intervention Group Prior to Randomization [After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin]

   Serum AT-III (% activity) will be compared between the control group and the intervention group patients (combined) after the third dose of enoxaparin 30 mg every 12 hours once initiated at the discretion of the trauma service per current VTE prophylaxis protocol

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Multi-system trauma

• Anticipated length of stay of at least 72 hours

• At high risk (risk adjustment profile [RAP] >= 5) and initiated on enoxaparin 30 mg every 12 hours per VTE prophylaxis protocol

• No counterindication to trauma team VTE prophylaxis protocol (e.g., intracranial bleeding, incomplete spinal cord injury with hematoma within 24 hours post injury, ongoing hemorrhage, uncorrected coagulopathy, >= grade IV liver or spleen injury, intraocular injury)

Exclusion Criteria:

• Renal dysfunction (creatinine clearance < 30 mL/min or on continuous renal replacement therapy)

• Weight < 50 kg or > 150 kg

• Platelet count < 50,000

• Allergy to heparin or low molecular weight heparin

• On therapeutic anticoagulation on admission or requiring it within 24 hours of admission

• Isolated intracranial hemorrhage

• Known hyperbilirubinemia (serum bilirubin > 6.6 mg/dL)

• Pregnancy

• Incarceration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45216

Sponsors and Collaborators

• University of Cincinnati
• United States Air Force

Investigators

• Principal Investigator: Molly Droege, PharmD, UC Health - University of Cincinnati Medical Center

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Nov 30, 2016

More Information

Publications

None provided.

• Responsible Party: Molly Droege, Clinical Pharmacy Specialist, Trauma, Surgery, and Orthopedics, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT02412982
• Other Study ID Numbers: Droege2015
• First Posted: Apr 9, 2015
• Last Update Posted: Oct 25, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Thromboembolism; Venous Thromboembolism; Wounds and Injuries; Enoxaparin; Enoxaparin sodium

Study Results

Participant Flow

Pre-assignment Detail	1496 screened for eligibility. 1393 excluded. 51 in control group (anti-Xa 0.1 IU/mL or greater); 52 in intervention group (anti-Xa < 0.1 IU/mL) 52 patients in the intervention group underwent 1:1 randomization to the two intervention study arms: 26 patients in 40 mg every 12 hours with escalation to 50 mg every 12 hours and 26 patients in 30 mg every 8 hours.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 51 4 with AT-III not collected so 47 included in primary outcome analysis	Patients with serum anti-Xa < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 52 1 patient withdrew consent; 2 patients did not have AT-III collected. 49 total included in primary outcome analyses.
Period Title: Primary Endpoint
STARTED	51	52
COMPLETED	47	49
NOT COMPLETED	4	3
Period Title: Primary Endpoint
STARTED	0	52
COMPLETED	0	51
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Control: Serum Anti-Xa >= 0.1 IU/mL	Intervention: Serum Anti-Xa < 0.1 IU/mL	Total
Arm/Group Description	Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours	Patients with serum anti-Xa level < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours	Total of all reporting groups
Overall Participants	47	51	98
Age (years) [Median (Inter-Quartile Range) ]
Age	38	41	41
Sex: Female, Male (Count of Participants)
Female	18 38.3%	13 25.5%	31 31.6%
Male	29 61.7%	38 74.5%	67 68.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Initial AT-III Activity -- Control Group vs. Intervention Group Prior to Randomization
Description	Serum AT-III (% activity) will be compared between the control group and the intervention group patients (combined) after the third dose of enoxaparin 30 mg every 12 hours once initiated at the discretion of the trauma service per current VTE prophylaxis protocol
Time Frame	After third dose of enoxaparin 30mg q12h, which will typically be on Day 2 of enoxaparin

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 51 4 with AT-III not collected so 47 included in primary outcome analysis	Patients with serum anti-Xa < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 52 1 patient withdrew consent; 2 patients did not have AT-III collected. 49 total included in primary outcome analyses.
Measure Participants	47	49
Median (Inter-Quartile Range) [Percent AT-III activity (%)]	87	82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	During patient enrollment up to 28 days, while inpatient
Arm/Group Title	Control Group		Intervention Group
Arm/Group Description	Patients with serum anti-Xa level >= 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 51 4 with AT-III not collected so 47 included in primary outcome analysis		Patients with serum anti-Xa < 0.1 IU/mL after third dose of enoxaparin 30 mg every 12 hours n = 52 1 patient withdrew consent; 2 patients did not have AT-III collected. 49 total included in primary outcome analyses.
All Cause Mortality
	Control Group		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/52 (0%)
Serious Adverse Events
	Control Group		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	Control Group		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/51 (0%)

Limitations/Caveats

Underpowered; See full results and manuscript listed in citation section.

More Information

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.