Clinical trial NCT03244020: LMWH Vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
Official title: Low Molecular Weight Heparin Versus Aspirin for Venous Thromboembolism Prophylaxis in Orthopaedic Oncology
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Sarcoma
Soft Tissue Sarcoma
Bone Sarcoma
Bone Metastases
Venous Thromboembolism
Hematoma
Anticoagulant-induced Bleeding
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2017-08-09
Enrollment: 2868
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility criteria: Patients will first be evaluated for inclusion in a master observational study with the following inclusion criteria:

1. Age ≥18 years
2. Prior or planned surgery on the pelvis or lower extremity
3. Fulfills one of the following:

   a. Cohort A: Metastatic osseous disease, undergoing: i. Endoprosthetic reconstruction ii. Curettage, cement packing, and fixation with nails, plates, and/or screws iii. Intramedullary nail fixation only b. Cohort B: Primary bone sarcoma, undergoing wide resection, amputation, or reconstruction with endoprosthesis, allograft, or allograft-prosthesis composite (APC).

   c. Cohort C: Primary soft tissue sarcoma ≥5 cm in diameter, undergoing wide resection
4. Anticoagulation therapy was received or is planned.

In addition to fulfilling all the inclusion criteria in Part 1 of this study, participants must also not meet any of the below exclusion criteria in order to be eligible for randomization to either aspirin or LMWH.

Exclusion Criteria:

1. Documented prior history of VTE.
2. Preoperative use of therapeutic or prophylactic chemical anticoagulation at the time of surgery.
3. Documented allergy/adverse reaction to either of the two study drugs.
4. Presence of inferior vena cava (IVC) filter.
5. Known, diagnosed hypercoagulable state (other than malignancy).
6. Inability to receive chemical anticoagulation.
7. Preoperative use of full-strength aspirin 325 mg daily; patients already taking aspirin 81 mg daily will not be excluded.
8. Inability for the patient him/herself to give informed consent due to delirium, dementia, or any other reason.
9. Pregnancy
10. Fear of needles that prevents administration of LMWH.
11. Inability to administer medications via needles.
12. For patients with metastatic osseous disease, a Khorana score of ≥3.

Pregnancy testing, via a urine or blood test, is a routine part of pre-operative laboratory testing in patients scheduled to undergo orthopaedic surgeries. Attending surgeons may also choose to exclude any patient from randomization at their discretion.

Primary outcomes:
measure: Venous thromboembolism
timeFrame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively
Secondary outcomes:
measure: Hematoma formation
timeFrame: 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
timeFrame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively
measure: Early chemoprophylaxis stop
timeFrame: Up to 4 weeks post operatively
measure: Infection
timeFrame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles Health
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: New Orleans
country: United States
facility: Louisiana State University Health
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Santiago Lozano-Calderon
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Columbia
country: United States
facility: University of Missouri-Columbia Cancer Care
state: Missouri
city: Camden
country: United States
facility: Cooper University Health Care
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: Massachusetts General Hospital
name: Santiago A Lozano-Calderon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: