LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology

Официальное название

Low Molecular Weight Heparin Versus Aspirin for Venous Thromboembolism Prophylaxis in Orthopaedic Oncology

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Aspirin 325mg
  Aspirin 325 mg by mouth once daily
• Препарат Enoxaparin 40Mg/0.4mL Prefilled Syringe
  Enoxaparin 40 mg subcutaneous injection once daily

Первичные конечные точки

• Venous thromboembolism [Срок оценки: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively]

Вторичные конечные точки (4)

• Hematoma formation [Срок оценки: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively]
• Complication requiring return to operating room [Срок оценки: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively]
• Early chemoprophylaxis stop [Срок оценки: Up to 4 weeks post operatively]
• Infection [Срок оценки: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively]

Критерии участия

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

• Age ≥18 years
• Prior or planned surgery on the pelvis or lower extremity
• 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

• 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.

Критерии исключения

• Documented prior history of VTE.
• Preoperative use of therapeutic or prophylactic chemical anticoagulation at the time of surgery.
• Documented allergy/adverse reaction to either of the two study drugs.
• Presence of inferior vena cava (IVC) filter.
• Known, diagnosed hypercoagulable state (other than malignancy).
• Inability to receive chemical anticoagulation.
• Preoperative use of full-strength aspirin 325 mg daily; patients already taking aspirin 81 mg daily will not be excluded.
• Inability for the patient him/herself to give informed consent due to delirium, dementia, or any other reason.
• Pregnancy
• Fear of needles that prevents administration of LMWH.
• Inability to administer medications via needles.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 10 центров

• University of California Los Angeles Health — Los Angeles
• Moffitt Cancer Center — Tampa
• Louisiana State University Health — New Orleans
• Johns Hopkins University — Baltimore
• Santiago Lozano-Calderon — Boston
• Brigham and Women's Hospital — Boston
• Beth Israel Deaconess Medical Center — Boston
• University of Missouri-Columbia Cancer Care — Columbia
• … и ещё 2 центра

Идентификаторы

NCT: NCT03244020 · 2017P000382

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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