A Different Approach to Preventing Thrombosis

Phase 3

Completed

• Conditions: Pulmonary Embolism; Venous Thromboembolism
• Interventions: Drug: VTE prophylaxis with Enoxaparin 30mg BID; Drug: VTE prophylaxis with Aspirin 81mg BID

• Registration Number: NCT02774265
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

The purpose of this study is to perform a pragmatic randomized controlled trial to compare the use of low molecular weight heparin (LMWH, lovenox, enoxaparin) versus acetylsalicylic acid (ASA) for venous thromboembolism (VTE) prophylaxis in patients with high-risk lower extremity fractures.

Detailed Description

Purpose:

To perform a pragmatic randomized controlled trial of the use of low molecular weight heparin (LMWH, enoxaparin, lovenox) versus Aspirin (ASA) for VTE prophylaxis in patients with high-risk extremity fractures.

Specific Aims:

1. To compare the bleeding complication outcomes associated with LMWH versus ASA in patients receiving VTE prophylaxis following high-risk lower extremity fractures.

2. To compare the incidence of clinically important VTE events associated with LMWH versus ASA for VTE prophylaxis in patients receiving VTE prophylaxis following high-risk lower extremity fractures.

3. To compare the 6-month treatment costs associated with VTE prophylaxis using either LMWH or ASA for high-risk lower extremity fracture patients

Hypothesis:

1. Among patients with high risk lower extremity fractures receiving VTE prophylaxis, the rate of bleeding complications will be lower for patients receiving ASA compared to those receiving LMWH.

2. Among patients with high risk lower extremity fractures receiving VTE prophylaxis, the rate of VTE for patients receiving ASA will be no greater than those receiving LMWH.

3. Among patients with high risk lower extremity fractures receiving VTE prophylaxis, the 6-month treatment costs will be lower for patients receiving ASA compared to those receiving LMWH.

Methods/Outcomes:

A randomized controlled trial will be conducted to assess the use of LMWH versus ASA for VTE prophylaxis in patients with high-risk extremity fractures.

The aim-specific outcomes to be collected are as follows:

1. A composite of the following major bleeding related complications:

1. Fatal bleeding into a critical organ (retroperitoneal, intracranial, intraocular, intraspinal)

2. Clinically overt bleed with a \> 2g/dL drop in Hb or requiring \> 2U transfusion

3. Wound drainage or hematoma requiring reoperation

4. Diagnosis of deep surgical site infection

2. VTE Events defined as a composite of any symptomatic proximal DVT (in the femoral or popliteal vessels), or PE (central, segmental or subsegmental). All VTE events will be confirmed using multiplanar CT scan or formal venous duplex exam.

3. Cost of VTE prophylaxis treatment, VTE events and bleeding related complications.

Data Collection:

Patients meeting inclusion/exclusion criteria will be prospectively randomized to one of two treatment arms. Block randomization will be used. Patients will receive VTE prophylaxis as allocated, and followed for their index hospitalization and a 3month period post discharge for VTE events and bleeding complications. Outcome data will be prospectively collected during index hospitalization, and at 2 weeks and 3 months post discharge, and blind analysis and interpretation of results will be performed at 50% and 100% recruitment.

Data Analysis:

All data will be reported as mean and standard deviations for continuous variables and proportions and percentages for categorical data. Kaplan-Meier survival and Cox proportional hazard analysis will be completed for time to VTE and bleeding complication outcomes. Sub-group analysis will include Injury Severity Score and fracture location. An independent Data Safety and Monitoring Committee will complete interim analysis at 50% recruitment. A cost analysis will be conducted using a 6month and lifetime time horizon with a societal perspective. Component costs will consist of: VTE prophylaxis costs, unscheduled follow-ups, emergency room visit, hospital admission or unscheduled repeat surgical intervention for VTE or bleeding complications.

Study Treatment Arms:

1. VTE prophylaxis with Enoxaparin 30mg SC BID

2. VTE prophylaxis with ASA 81mg PO BID

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-05-10
• Study First Submitted QC: 2016-05-12
• Study First Posted: 2016-05-17
• Primary Completion: 2017-05
• Study Completion: 2017-09
• Results First Submitted: 2018-06-27
• Results First Submitted QC: 2018-06-27
• Results First Posted: 2018-07-24
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-03
• Last Update Posted: 2022-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 329

Inclusion Criteria

• All patients treated at a level-1 trauma center with any one or more of the following injuries: Pelvis fracture (operative or non-operative), Acetabulum fracture (operative or non-operative), or any operative extremity fracture (proximal to metatarsals/carpals)
• Age greater than or equal to 18 years old

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Exclusion Criteria

• Patients receiving pre-existing confounding prophylaxis or therapeutic anticoagulation (not to include anti-platelet agents) prior to admission or those receiving greater than one dose of LMWH since injury
• Patients with pre-existing coagulopathy
• Patients with a previous history of VTE within the last 6 months
• Patients who are pregnant
• Patients with CNS or spinal cord injury with potential need for further neurosurgical intervention precluding anticoagulation with aspirin
• Patients with active bleeding precluding the use of anticoagulation
• Impaired creatinine clearance <30ml/min at the time of randomization
• History of Heparin Induced Thrombocytopenia or ASA or NSAID allergy
• Prisoners
• Non-english speaking patients
• Patients who have an indication for therapeutic anticoagulation
• Patients deemed inappropriate for inclusion in the study by their treating physician. Reason must be documented
• Patients who would not normally receive VTE prophylaxis for their injury

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VTE prophylaxis with Enoxaparin 30mg BID	VTE prophylaxis with Enoxaparin 30mg BID	The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID.
VTE prophylaxis with Aspirin 81mg BID	VTE prophylaxis with Aspirin 81mg BID	The group receiving VTE prophylaxis with ASA 81mg PO BID

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-related Bleeding Events as Assessed by the Need for Blood Transfusions and Procedures for Bleeding Complications After Initiation of the Study Medication.	90 days	Includes a greater than 2g/dL drop in hemoglobin, blood transfusion, hematoma evacuation, re-operation for a deep surgical site infection or minor procedure for bleeding and GI bleed

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Pulmonary Embolism Events	90 days	Bases on imaging obtained for symptoms.
Number of Participants With Deep Venous Thromboembolism	90 days	DVT and how the diagnosis was made will be recorded. The number of events in participants in each arm will be compared to evaluate efficacy.

Trial Locations

Locations (1)

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States