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Low Molecular Weight Heparin (LMWH) vs Aspirin for Venous Thromboembolism (VTE) Prophylaxis in Orthopaedic Oncology

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ClinicalTrials.gov Identifier: NCT03244020
Recruitment Status : Enrolling by invitation
First Posted : August 9, 2017
Last Update Posted : February 25, 2021
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Information provided by (Responsible Party):
Santiago Lozano-Calderon, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE August 5, 2017
First Posted Date  ICMJE August 9, 2017
Last Update Posted Date February 25, 2021
Actual Study Start Date  ICMJE February 16, 2018
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2017)
Venous thromboembolism [ Time Frame: up to 6 months post operatively ]
Deep venous thrombosis; pulmonary embolus
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2017)
  • Hematoma formation [ Time Frame: up to 6 months post operatively ]
  • Complication requiring return to operating room [ Time Frame: up to 6 months post operatively ]
    Return to operating room for any reason related to the original surgery
  • Early chemoprophylaxis stop [ Time Frame: up to 4 weeks post operatively ]
    ASA or LMWH stopped prior to 4 weeks post operatively by surgeon for any reason
  • Infection [ Time Frame: up to 6 months post operatively ]
    Infection requiring any sort of treatment (antibiotics alone, return to operating room)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Molecular Weight Heparin (LMWH) vs Aspirin for Venous Thromboembolism (VTE) Prophylaxis in Orthopaedic Oncology
Official Title  ICMJE Low Molecular Weight Heparin Versus Aspirin for Venous Thromboembolism Prophylaxis in Orthopaedic Oncology
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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.
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Sarcoma
  • Soft Tissue Sarcoma
  • Bone Sarcoma
  • Bone Metastases
  • Venous Thromboembolism
  • Hematoma
  • Anticoagulant-induced Bleeding
Intervention  ICMJE
  • Drug: Aspirin 325mg
    Aspirin 325 mg by mouth once daily
    Other Name: ASA
  • Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe
    Enoxaparin 40 mg subcutaneous injection once daily
    Other Name: Lovenox
Study Arms  ICMJE
  • Experimental: LMWH for Soft Tissue Sarcoma
    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
    Intervention: Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe
  • Experimental: ASA for Soft Tissue Sarcoma
    Patients undergoing surgery for pelvic/lower extremity soft tissue sarcomas and are randomized to aspirin 325 mg po daily for VTE prophylaxis
    Intervention: Drug: Aspirin 325mg
  • Experimental: LMWH for Primary Bone Tumor
    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
    Intervention: Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe
  • Experimental: ASA for Primary Bone Tumor
    Patients undergoing surgery for pelvic/lower extremity primary bone tumor and are randomized to aspirin 325 mg po daily for VTE prophylaxis
    Intervention: Drug: Aspirin 325mg
  • Experimental: LMWH for Metastatic Disease
    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
    Intervention: Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe
  • Experimental: ASA for Metastatic Disease
    Patients undergoing surgery for pelvic/lower extremity metastatic bone disease and are randomized to aspirin 325 mg po daily for VTE prophylaxis
    Intervention: Drug: Aspirin 325mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: February 13, 2020)
1434
Original Estimated Enrollment  ICMJE
 (submitted: August 5, 2017)
2868
Estimated Study Completion Date  ICMJE July 1, 2024
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with metastatic osseous disease of the lower extremities or pelvis treated with endoprosthetic reconstruction, curettage and cement packing with intramedullary nail fixation and/or plate and screws, or intramedullary nail fixation only.
  • Patients with primary bone sarcomas of the lower extremities or pelvis treated with wide resections and amputations or reconstruction with endoprosthesis, allografts, or allograft prosthetic composites.
  • Patients with soft tissue sarcomas of the lower extremities or pelvis measuring more than 8 cm in size, deep to the fascia levels, treated with preoperative or postoperative radiation, plus/minus preoperative and/or postoperative chemotherapy, receiving surgery with wide margins, followed by primary closure, closure with free or rotational, and/or skin graft. (478 patients per arm)

Exclusion Criteria:

  • Documented prior history of VTE
  • Pre-operative use of therapeutic or prophylactic chemical anti-coagulation at the time of surgery (not including ASA 81 mg)
  • Documented allergy/adverse reaction to either of the two study drugs
  • Presence of an inferior vena cava (IVC) filter
  • Known diagnosed hypercoagulable state (other than malignancy)
  • Inability to receive chemical anticoagulation
  • Pre-operative use of full strength aspirin 325 milligrams (mg) daily
  • Inability for the patient him/herself to give informed consent due to delirium, dementia, or any other reason.
  • Pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03244020
Other Study ID Numbers  ICMJE 2017P000382
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Santiago Lozano-Calderon, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE
  • Brigham and Women's Hospital
  • Beth Israel Deaconess Medical Center
Investigators  ICMJE
Principal Investigator: Santiago A Lozano-Calderon, MD, PhD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP