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ADAPT: A Different Approach to Preventing Thrombosis

Sponsor
University of Maryland, Baltimore (Other)
Overall Status
Completed
CT.gov ID
NCT02774265
Collaborator
(none)
329
Enrollment
1
Location
2
Arms
20
Actual Duration (Months)
16.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: VTE prophylaxis with Enoxaparin 30mg BID
  • Drug: VTE prophylaxis with Aspirin 81mg BID
 Phase 3

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:

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

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

  4. Wound drainage or hematoma requiring reoperation

  5. Diagnosis of deep surgical site infection

  6. 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.

  7. 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 Design

Study Type:
Interventional
Actual Enrollment :
329 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
A Different Approach to Preventing Thrombosis (ADAPT): A Randomized Controlled Trial Comparing Low Molecular Weight Heparin to Acetylsalicylic Acid in Orthopedic Trauma Patients
Actual Study Start Date :
Jan 1, 2016
Actual Primary Completion Date :
May 1, 2017
Actual Study Completion Date :
Sep 1, 2017

Arms and Interventions

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)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. Number of Participants With Pulmonary Embolism Events [90 days]

      Bases on imaging obtained for symptoms.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Maryland Medical Center Baltimore Maryland United States 21201

    Sponsors and Collaborators

    • University of Maryland, Baltimore

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Deborah Stein, Professor of Surgery, Chief of Trauma, University of Maryland, Baltimore
    ClinicalTrials.gov Identifier:
    NCT02774265
    Other Study ID Numbers:
    • HP-00065750
    First Posted:
    May 17, 2016
    Last Update Posted:
    Jan 5, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Deborah Stein, Professor of Surgery, Chief of Trauma, University of Maryland, Baltimore
    Fracture
    Prophylaxis
    Additional relevant MeSH terms:
    Pulmonary Embolism
    Thrombosis
    Embolism
    Thromboembolism
    Venous Thromboembolism
    Aspirin
    Heparin
    Enoxaparin
    Heparin, Low-Molecular-Weight
    Tinzaparin
    Dalteparin

    Study Results

    Participant Flow

    Recruitment Details We recruited inpatients admitted between January 19, 2016 and November 1, 2016.
    Pre-assignment Detail
    Arm/Group Title VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID
    Arm/Group Description The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID. 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. The group receiving VTE prophylaxis with ASA 81mg PO BID 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.
    Period Title: Overall Study
    STARTED 164 165
    COMPLETED 151 159
    NOT COMPLETED 13 6

    Baseline Characteristics

    Arm/Group Title VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID Total
    Arm/Group Description The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID. 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. The group receiving VTE prophylaxis with ASA 81mg PO BID 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. Total of all reporting groups
    Overall Participants 164 165 329
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    45.4
    (20.4)
    48
    (18.6)
    46.7
    (19.5)
    Sex: Female, Male (Count of Participants)
    Female
    45
    27.4%
    61
    37%
    106
    32.2%
    Male
    119
    72.6%
    104
    63%
    223
    67.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    53
    32.3%
    45
    27.3%
    98
    29.8%
    White
    97
    59.1%
    106
    64.2%
    203
    61.7%
    More than one race
    6
    3.7%
    3
    1.8%
    9
    2.7%
    Unknown or Not Reported
    8
    4.9%
    11
    6.7%
    19
    5.8%
    Current smoker (Count of Participants)
    Count of Participants [Participants]
    62
    37.8%
    65
    39.4%
    127
    38.6%

    Outcome Measures

    1. Primary Outcome
    Title 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.
    Description 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
    Time Frame 90 days

    Outcome Measure Data

    Analysis Population Description
    As described in Participant Flow
    Arm/Group Title VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID
    Arm/Group Description The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID. 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. The group receiving VTE prophylaxis with ASA 81mg PO BID 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.
    Measure Participants 164 165
    Count of Participants [Participants]
    52
    31.7%
    53
    32.1%
    2. Secondary Outcome
    Title Number of Participants With Deep Venous Thromboembolism
    Description 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.
    Time Frame 90 days

    Outcome Measure Data

    Analysis Population Description
    same as flow chart
    Arm/Group Title VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID
    Arm/Group Description The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID. 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. The group receiving VTE prophylaxis with ASA 81mg PO BID 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.
    Measure Participants 164 165
    Count of Participants [Participants]
    5
    3%
    9
    5.5%
    3. Secondary Outcome
    Title Number of Participants With Pulmonary Embolism Events
    Description Bases on imaging obtained for symptoms.
    Time Frame 90 days

    Outcome Measure Data

    Analysis Population Description
    As per flow sheet
    Arm/Group Title VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID
    Arm/Group Description The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID. 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. The group receiving VTE prophylaxis with ASA 81mg PO BID 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.
    Measure Participants 164 165
    Count of Participants [Participants]
    6
    3.7%
    2
    1.2%

    Adverse Events

    Time Frame 90 days post injury
    Adverse Event Reporting Description Adverse events as described by our IRB reporting protocol include only unexpected adverse events. Since study outcomes like bleeding and venous thromboembolism are expected, measured outcomes, these are not included.
    Arm/Group Title VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID
    Arm/Group Description The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID. 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. The group receiving VTE prophylaxis with ASA 81mg PO BID 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.
    All Cause Mortality
    VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/164 (1.8%) 3/165 (1.8%)
    Serious Adverse Events
    VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/164 (0%) 0/165 (0%)
    Other (Not Including Serious) Adverse Events
    VTE Prophylaxis With Enoxaparin 30mg BID VTE Prophylaxis With Aspirin 81mg BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/164 (0%) 0/165 (0%)

    Limitations/Caveats

    [Not Specified]

    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.

    Results Point of Contact

    Name/Title Dr. Bryce Haac
    Organization University of Maryland Medical Center
    Phone 410-328-3495
    Email bhaac@som.umaryland.edu
    Responsible Party:
    Deborah Stein, Professor of Surgery, Chief of Trauma, University of Maryland, Baltimore
    ClinicalTrials.gov Identifier:
    NCT02774265
    Other Study ID Numbers:
    • HP-00065750
    First Posted:
    May 17, 2016
    Last Update Posted:
    Jan 5, 2022
    Last Verified:
    Jan 1, 2022