A Different Approach to Preventing Thrombosis (ADAPT)

January 3, 2022 updated by: Deborah Stein, University of Maryland, Baltimore

A Different Approach to Preventing Thrombosis (ADAPT): A Randomized Controlled Trial Comparing Low Molecular Weight Heparin to Acetylsalicylic Acid in Orthopedic Trauma Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

329

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: VTE prophylaxis with Enoxaparin 30mg BID
The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID.
Drug: VTE prophylaxis with Enoxaparin 30mg BID
Patients will receive Enoxaparin 30mg BID for DVT prophylaxis and will be followed to determine the efficacy, safety and cost when used for VTE prophylaxis in high-risk orthopedic traumas administered for the length of time indicated by standard of care based on the injury.
Other Names:
  • Lovenox
  • Low Molecular Weight Heparin (LMWH)
ACTIVE_COMPARATOR: VTE prophylaxis with Aspirin 81mg BID
The group receiving VTE prophylaxis with ASA 81mg PO BID
Drug: VTE prophylaxis with Aspirin 81mg BID
Patients will receive Aspirin 81mg BID for DVT prophylaxis and will be followed to determine the efficacy, safety and cost when used for VTE prophylaxis in high-risk orthopedic traumas administered for the length of time indicated by standard of care based on the injury.
Other Names:
  • ASA (Acetylsalicylic Acid)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Deep Venous Thromboembolism
Time Frame: 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.
90 days
Number of Participants With Pulmonary Embolism Events
Time Frame: 90 days
Bases on imaging obtained for symptoms.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Investigators

  • Principal Investigator: Deborah Stein, MD, MPH, R. Adams Cowley Shock Trauma Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 1, 2016

Primary Completion (ACTUAL)

May 1, 2017

Study Completion (ACTUAL)

September 1, 2017

Study Registration Dates

First Submitted

May 10, 2016

First Submitted That Met QC Criteria

May 12, 2016

First Posted (ESTIMATE)

May 17, 2016

Study Record Updates

Last Update Posted (ACTUAL)

January 5, 2022

Last Update Submitted That Met QC Criteria

January 3, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00065750

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data will be shared as aggregate data only to protect the identity of individual participants.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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