<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03244020</url>
  </required_header>
  <id_info>
    <org_study_id>2017P000382</org_study_id>
    <nct_id>NCT03244020</nct_id>
  </id_info>
  <brief_title>Low Molecular Weight Heparin (LMWH) vs Aspirin for Venous Thromboembolism (VTE) Prophylaxis in Orthopaedic Oncology</brief_title>
  <official_title>Low Molecular Weight Heparin Versus Aspirin for Venous Thromboembolism Prophylaxis in Orthopaedic Oncology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aspirin and low molecular weight heparin (LMWH) are both commonly employed pharmacologic&#xD;
      methods of venous thromboembolism (VTE) prophylaxis after orthopaedic surgery. Data comparing&#xD;
      these two methods of VTE prophylaxis in patients undergoing pelvic/lower extremity&#xD;
      orthopaedic surgery for malignancy are lacking, however, as compared to the data and&#xD;
      guidelines present for VTE chemoprophylaxis after joint arthroplasty and hip fracture&#xD;
      surgery. In this clinical trial, our specific aim is to compare the post operative incidence&#xD;
      of VTE between patients receiving aspirin and LMWH after pelvic/lower extremity orthopaedic&#xD;
      oncology procedures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lower extremity orthopaedic surgery and malignancy are both known major risk factors for&#xD;
      venous thromboembolism (VTE). Guidelines from high quality data exist with regards to VTE&#xD;
      prophylaxis in patients undergoing orthopaedic surgery, particularly joint arthroplasty. Far&#xD;
      fewer data are available regarding the efficacy of various methods of pharmacologic VTE&#xD;
      prophylaxis in patients undergoing surgery for primary or metastatic musculoskeletal&#xD;
      malignancies as malignancy itself is known to confer a hypercoagulable state. The existing&#xD;
      data, including published data from our institution, are almost exclusively from&#xD;
      retrospective studies. Given the limited external validity of existing guidelines and&#xD;
      limitations inherent in applying data from retrospective studies, a randomized, prospective&#xD;
      study comparing two of the most common methods of pharmacologic VTE prophylaxis would help to&#xD;
      guide clinical care of this patient population. In addition, large dead spaces susceptible to&#xD;
      hematoma formation are often created from tumor resections in orthopaedic oncology. Our&#xD;
      retrospective data suggest that hematoma formation may be an independent predictor of&#xD;
      infection. An important risk of chemical VTE prophylaxis is an increased incidence of&#xD;
      bleeding into these dead spaces, leading to hematomas. This illustrates the complexity of&#xD;
      selecting a method of VTE prophylaxis in patients at both high risk of VTE and hematoma&#xD;
      formation and the need for high quality data to guide clinical decision-making in this&#xD;
      patient population.&#xD;
&#xD;
      The specific aim of this study is to compare the post operative incidence of symptomatic deep&#xD;
      vein thrombosis (DVT) and pulmonary embolus (PE) between patients who receive low molecular&#xD;
      weight heparin (LMWH) versus aspirin for prophylaxis after having undergone pelvic or lower&#xD;
      extremity orthopaedic oncology surgery (primary bone sarcomas, soft tissue sarcomas, and&#xD;
      metastatic osseous disease).&#xD;
&#xD;
      Our secondary aim is to compare the incidence of hematoma formation and wound complications&#xD;
      between these methods of pharmacologic prophylaxis in the aforementioned patient population.&#xD;
&#xD;
      Our hypothesis is that there is no significant difference in the incidence rate of&#xD;
      symptomatic DVT/PE in patients administered LMWH versus aspirin for prophylaxis; however&#xD;
      there may exist a difference in the rate of wound complications between these prophylaxis&#xD;
      methods.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">February 16, 2018</start_date>
  <completion_date type="Anticipated">July 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Three separate patient categories are being investigated in this trial. All patients are undergoing pelvic and/or lower extremity surgery for one of three possible conditions: 1) soft tissue sarcoma; 2) primary bone sarcoma; 3) metastatic bone disease. Within each of these groups, patients will be randomized to either aspirin or low molecular weight heparin (enoxaparin) for venous thromboembolism prophylaxis post operatively.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Venous thromboembolism</measure>
    <time_frame>Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively</time_frame>
    <description>Deep venous thrombosis; pulmonary embolus</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hematoma formation</measure>
    <time_frame>Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complication requiring return to operating room</measure>
    <time_frame>Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively</time_frame>
    <description>Return to operating room for any reason related to the original surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early chemoprophylaxis stop</measure>
    <time_frame>Up to 4 weeks post operatively</time_frame>
    <description>ASA or LMWH stopped prior to 4 weeks post operatively by surgeon for any reason</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infection</measure>
    <time_frame>Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively</time_frame>
    <description>Infection requiring any sort of treatment (antibiotics alone, return to operating room)</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">1434</enrollment>
  <condition>Sarcoma</condition>
  <condition>Soft Tissue Sarcoma</condition>
  <condition>Bone Sarcoma</condition>
  <condition>Bone Metastases</condition>
  <condition>Venous Thromboembolism</condition>
  <condition>Hematoma</condition>
  <condition>Anticoagulant-induced Bleeding</condition>
  <arm_group>
    <arm_group_label>LMWH for Soft Tissue Sarcoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergoing surgery for pelvic/lower extremity soft tissue sarcomas and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ASA for Soft Tissue Sarcoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergoing surgery for pelvic/lower extremity soft tissue sarcomas and are randomized to aspirin 325 mg po daily for VTE prophylaxis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LMWH for Primary Bone Tumor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergoing surgery for pelvic/lower extremity primary bone tumor and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ASA for Primary Bone Tumor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergoing surgery for pelvic/lower extremity primary bone tumor and are randomized to aspirin 325 mg po daily for VTE prophylaxis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LMWH for Metastatic Disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergoing surgery for pelvic/lower extremity metastatic bone disease and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ASA for Metastatic Disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergoing surgery for pelvic/lower extremity metastatic bone disease and are randomized to aspirin 325 mg po daily for VTE prophylaxis</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin 325mg</intervention_name>
    <description>Aspirin 325 mg by mouth once daily</description>
    <arm_group_label>ASA for Metastatic Disease</arm_group_label>
    <arm_group_label>ASA for Primary Bone Tumor</arm_group_label>
    <arm_group_label>ASA for Soft Tissue Sarcoma</arm_group_label>
    <other_name>ASA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin 40Mg/0.4mL Prefilled Syringe</intervention_name>
    <description>Enoxaparin 40 mg subcutaneous injection once daily</description>
    <arm_group_label>LMWH for Metastatic Disease</arm_group_label>
    <arm_group_label>LMWH for Primary Bone Tumor</arm_group_label>
    <arm_group_label>LMWH for Soft Tissue Sarcoma</arm_group_label>
    <other_name>Lovenox</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with metastatic osseous disease of the lower extremities or pelvis treated&#xD;
             with endoprosthetic reconstruction, curettage and cement packing with intramedullary&#xD;
             nail fixation and/or plate and screws, or intramedullary nail fixation only.&#xD;
&#xD;
          -  Patients with primary bone sarcomas of the lower extremities or pelvis treated with&#xD;
             wide resections and amputations or reconstruction with endoprosthesis, allografts, or&#xD;
             allograft prosthetic composites.&#xD;
&#xD;
          -  Patients with soft tissue sarcomas of the lower extremities or pelvis measuring more&#xD;
             than 8 cm in size, deep to the fascia levels, treated with preoperative or&#xD;
             postoperative radiation, plus/minus preoperative and/or postoperative chemotherapy,&#xD;
             receiving surgery with wide margins, followed by primary closure, closure with free or&#xD;
             rotational, and/or skin graft. (478 patients per arm)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Documented prior history of VTE&#xD;
&#xD;
          -  Pre-operative use of therapeutic or prophylactic chemical anti-coagulation at the time&#xD;
             of surgery (not including ASA 81 mg)&#xD;
&#xD;
          -  Documented allergy/adverse reaction to either of the two study drugs&#xD;
&#xD;
          -  Presence of an inferior vena cava (IVC) filter&#xD;
&#xD;
          -  Known diagnosed hypercoagulable state (other than malignancy)&#xD;
&#xD;
          -  Inability to receive chemical anticoagulation&#xD;
&#xD;
          -  Pre-operative use of full strength aspirin 325 milligrams (mg) daily&#xD;
&#xD;
          -  Inability for the patient him/herself to give informed consent due to delirium,&#xD;
             dementia, or any other reason.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Fear of needles&#xD;
&#xD;
          -  Inability to administer medications via needles themselves&#xD;
&#xD;
          -  Situation in which the attending surgeon does not feel that randomization of a subject&#xD;
             would be appropriate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Santiago A Lozano-Calderon, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Santiago Lozano-Calderon</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 5, 2017</study_first_submitted>
  <study_first_submitted_qc>August 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>January 20, 2023</last_update_submitted>
  <last_update_submitted_qc>January 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Santiago Lozano-Calderon</investigator_full_name>
    <investigator_title>Instructor of Orthopaedic Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
    <mesh_term>Hematoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Enoxaparin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03244020
org study id: 2017P000382
nct id: NCT03244020
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Aspirin and low molecular weight heparin (LMWH) are both commonly employed pharmacologic
      methods of venous thromboembolism (VTE) prophylaxis after orthopaedic surgery. Data comparing
      these two methods of VTE prophylaxis in patients undergoing pelvic/lower extremity
      orthopaedic surgery for malignancy are lacking, however, as compared to the data and
      guidelines present for VTE chemoprophylaxis after joint arthroplasty and hip fracture
      surgery. In this clinical trial, our specific aim is to compare the post operative incidence
      of VTE between patients receiving aspirin and LMWH after pelvic/lower extremity orthopaedic
      oncology procedures.
Lower extremity orthopaedic surgery and malignancy are both known major risk factors for
      venous thromboembolism (VTE). Guidelines from high quality data exist with regards to VTE
      prophylaxis in patients undergoing orthopaedic surgery, particularly joint arthroplasty. Far
      fewer data are available regarding the efficacy of various methods of pharmacologic VTE
      prophylaxis in patients undergoing surgery for primary or metastatic musculoskeletal
      malignancies as malignancy itself is known to confer a hypercoagulable state. The existing
      data, including published data from our institution, are almost exclusively from
      retrospective studies. Given the limited external validity of existing guidelines and
      limitations inherent in applying data from retrospective studies, a randomized, prospective
      study comparing two of the most common methods of pharmacologic VTE prophylaxis would help to
      guide clinical care of this patient population. In addition, large dead spaces susceptible to
      hematoma formation are often created from tumor resections in orthopaedic oncology. Our
      retrospective data suggest that hematoma formation may be an independent predictor of
      infection. An important risk of chemical VTE prophylaxis is an increased incidence of
      bleeding into these dead spaces, leading to hematomas. This illustrates the complexity of
      selecting a method of VTE prophylaxis in patients at both high risk of VTE and hematoma
      formation and the need for high quality data to guide clinical decision-making in this
      patient population.

      The specific aim of this study is to compare the post operative incidence of symptomatic deep
      vein thrombosis (DVT) and pulmonary embolus (PE) between patients who receive low molecular
      weight heparin (LMWH) versus aspirin for prophylaxis after having undergone pelvic or lower
      extremity orthopaedic oncology surgery (primary bone sarcomas, soft tissue sarcomas, and
      metastatic osseous disease).

      Our secondary aim is to compare the incidence of hematoma formation and wound complications
      between these methods of pharmacologic prophylaxis in the aforementioned patient population.

      Our hypothesis is that there is no significant difference in the incidence rate of
      symptomatic DVT/PE in patients administered LMWH versus aspirin for prophylaxis; however
      there may exist a difference in the rate of wound complications between these prophylaxis
      methods.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Three separate patient categories are being investigated in this trial. All patients are undergoing pelvic and/or lower extremity surgery for one of three possible conditions: 1) soft tissue sarcoma; 2) primary bone sarcoma; 3) metastatic bone disease. Within each of these groups, patients will be randomized to either aspirin or low molecular weight heparin (enoxaparin) for venous thromboembolism prophylaxis post operatively.
primary purpose: Prevention
masking: None (Open Label)
measure: Venous thromboembolism
time frame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively
description: Deep venous thrombosis; pulmonary embolus
measure: Hematoma formation
time frame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively
measure: Complication requiring return to operating room
time frame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively
description: Return to operating room for any reason related to the original surgery
measure: Early chemoprophylaxis stop
time frame: Up to 4 weeks post operatively
description: ASA or LMWH stopped prior to 4 weeks post operatively by surgeon for any reason
measure: Infection
time frame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively
description: Infection requiring any sort of treatment (antibiotics alone, return to operating room)
arm group label: LMWH for Soft Tissue Sarcoma
arm group type: Experimental
description: Patients undergoing surgery for pelvic/lower extremity soft tissue sarcomas and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis
arm group label: ASA for Soft Tissue Sarcoma
arm group type: Experimental
description: Patients undergoing surgery for pelvic/lower extremity soft tissue sarcomas and are randomized to aspirin 325 mg po daily for VTE prophylaxis
arm group label: LMWH for Primary Bone Tumor
arm group type: Experimental
description: Patients undergoing surgery for pelvic/lower extremity primary bone tumor and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis
arm group label: ASA for Primary Bone Tumor
arm group type: Experimental
description: Patients undergoing surgery for pelvic/lower extremity primary bone tumor and are randomized to aspirin 325 mg po daily for VTE prophylaxis
arm group label: LMWH for Metastatic Disease
arm group type: Experimental
description: Patients undergoing surgery for pelvic/lower extremity metastatic bone disease and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis
arm group label: ASA for Metastatic Disease
arm group type: Experimental
description: Patients undergoing surgery for pelvic/lower extremity metastatic bone disease and are randomized to aspirin 325 mg po daily for VTE prophylaxis
intervention type: Drug
intervention name: Aspirin 325mg
description: Aspirin 325 mg by mouth once daily
arm group label: ASA for Metastatic Disease
arm group label: ASA for Primary Bone Tumor
arm group label: ASA for Soft Tissue Sarcoma
other name: ASA
intervention type: Drug
intervention name: Enoxaparin 40Mg/0.4mL Prefilled Syringe
description: Enoxaparin 40 mg subcutaneous injection once daily
arm group label: LMWH for Metastatic Disease
arm group label: LMWH for Primary Bone Tumor
arm group label: LMWH for Soft Tissue Sarcoma
other name: Lovenox
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Santiago A Lozano-Calderon, MD, PhD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Santiago Lozano-Calderon
investigator title: Instructor of Orthopaedic Surgery
mesh term: Sarcoma
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Hematoma
mesh term: Aspirin
mesh term: Enoxaparin
sharing ipd: No