Efficacy and Safety of Rivaroxaban in the Prevention of Venous Thromboembolism in Glioma Patients

December 25, 2023 updated by: Nanfang Hospital, Southern Medical University

Efficacy and Safety of Rivaroxaban in the Prevention of Venous Thromboembolism in Glioma Patients With Postoperative Lower Extremity Dyskinesia

Glioma is a common brain tumor with a high risk of venous thromboembolism during treatment, especially in the months after surgery. Postoperative lower extremity dyskinesia in patients with gliomas is considered as a high-risk factor for venous thromboembolism. Rivaroxaban, as an oral anticoagulants, has similar effect in the prevention and treatment of tumor-related venous thromboembolism compared to low molecular weight heparin. Given the lack of prospective supporting data, the efficacy and safety of rivaroxaban in the prevention of postoperative venous thromboembolism in glioma patients with postoperative lower extremity dyskinesia need to be established.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Venous thromboembolism (VTE) is a disorder in which blood clots abnormally in the veins, resulting in complete or incomplete blockage of blood vessels, including deep vein thrombosis and pulmonary embolism of the lower extremities, and is a common complication in patients with malignancy. In a retrospective analysis of the causes of death in patients with active cancer receiving chemotherapy, thromboembolic disease was the second leading cause of death, with VTE accounting for the vast majority. The risk of venous thromboembolism varies depending on the type of cancer, but it has been reported that the incidence of brain tumors can be greater than 20 percent per year, especially in the early postoperative period. High-grade gliomas are common brain tumors with a 20 to 30 percent risk of venous thrombosis during treatment, and postoperative lower extremity dysfunction in patients with high-grade gliomas is considered a high-risk factor for venous thrombosis. Because many high-grade gliomas are located in or adjacent to functional areas, such as frontopariparietal glioma, parietal glioma, thalamic glioma, and others, patients are more likely to develop limb dysfunction. Therefore, it is necessary to prevent venous thromboembolism for patients with high-grade glioma with lower extremity dysfunction after surgery.

Risk factors for venous thromboembolism can be divided into patient-related, tumor-related, and treatment-related. Patient-related factors include age >65 years, weight gain, hypertension, A or AB blood type, previous history of venous thrombosis or pulmonary embolism, and paraparesis. Risk factors associated with tumors include high-grade glioma, tumor diameter >5 cm, and residual tumor after surgery. Treatment-related risk factors include early postoperative period (within 30 days), surgery time >4 hours, chemotherapy, anti-vascular endothelial growth factor therapy, hormonal therapy, and central venous catheterization. Lower extremity dysfunction in patients with glioma is both tumor-related and treatment-related. In the past, clinicians did not routinely administer prophylactic anticoagulation to glioma patients with lower limb disorders because the use of anticoagulants would increase the chance of postoperative intracranial hemorrhage. However, it was reported that the risk of venous thromboembolism in patients with lower extremity dysfunction was 2.6 to 3.6 times than in those without lower extremity dysfunction, and recent studies have shown that the combination of perioperative compression stockings, pneumatic plantar venous pumps and low molecular weight heparin (LMWH) maximizes the prevention of venous thromboembolism in critically neurosurgical patients without a high risk of bleeding. Moreover, a previous randomized, double-blind prospective clinical trial evaluated the safety of heparin in the perioperative period of brain tumors, and the results suggested that the perioperative use of low-dose heparin in brain tumors was safe and effective, and did not increase the risk of bleeding compared with controls. Another meta-analysis further confirmed the safety of LMWH or unfractionated heparin for the prevention of venous thromboembolism after neurosurgery.

However, there are few studies on the use of LMWH in this population, and there is no consensus on the safety of LMWH for the prevention of venous thromboembolism in this population. A phase III randomized controlled trial in patients with high-grade glioma, initiated in 2002, evaluated the safety and efficacy of postoperative LMWH for the prevention of venous thromboembolism, suggesting that LMWH can reduce the occurrence of venous thrombosis but also increase the risk of bleeding. The Eastern Cooperative Oncology Group has also evaluated the use of LMWH for the prevention of glioblastoma, and the use of LMWH reduced thrombosis without increasing the probability of intracranial hemorrhage. In addition, the scale and number of cases in the above studies were small. Therefore, there is an urgent need to explore an effective and safe method to prevent postoperative venous thromboembolism in glioma patients with lower limb dysfunction.

Rivaroxaban is an oral anticoagulant that directly inhibits Xa and thrombin and is widely used in noncancer-associated VTE due to its oral availability, high bioavailability with no need for frequent coagulation monitoring. In the study of tumor-related VTE, rivaroxaban has preliminarily shown no less effect than LMWH in the prevention and treatment of venous thromboembolism. Mohamed et al. systematically reviewed and meta-analyzed the efficacy and complications of LMWH and rivaroxaban in cancer-related thrombosis, and the results suggested that rivaroxaban had a lower risk of VTE recurrence and all-cause mortality, and that the main bleeding risk was no different from that of LMWH. In a phase III SELECT-D pilot study comparing the efficacy and complications of cancer-related thrombosis with the two agents, rivaroxaban was associated with a low risk of VTE recurrence and a low risk of major and non-major bleeding. Therefore, rivaroxaban has a good role in the prevention of tumor-related VTE. And because of its convenience of being oral and not requiring frequent monitoring, it is of great significance for clinical treatment.

In summary, in view of the current lack of research on postoperative prophylactic anticoagulation therapy in patients with glioma, our center plans to lead a multi-center, randomized, double-blind controlled prospective clinical trial in glioma patients with lower limb dysfunction after surgery. To determine whether the addition of rivaroxaban has a more active preventive effect on postoperative venous thromboembolism, and to explore the safety of rivaroxaban in preventing postoperative venous thromboembolism in glioma patients lower limb dysfunction.

Study Type

Interventional

Enrollment (Estimated)

320

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Tianshi Que, M.D.
  • Phone Number: +86-020-61641806
  • Email: qtssjwk@126.com

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100070
        • Recruiting
        • Beijing Tiantan Hospital
        • Contact:
          • Lei Wang, M.D.
    • Fujian
      • Fuzhou, Fujian, China, 350001
        • Recruiting
        • Fujian Provincial Hospital
        • Contact:
          • Shihao Zheng, M.D.
    • Guangdong
      • Foshan, Guangdong, China, 528000
        • Recruiting
        • The first people's Hospital of Foshan
        • Contact:
          • Lianxu Cui, M.D.
      • Shantou, Guangdong, China, 515041
        • Recruiting
        • The First Affiliated Hospital of Shantou University Medical College
        • Contact:
          • Yiming Xu, M.D.
      • Shenzhen, Guangdong, China, 518116
        • Recruiting
        • Longgang Central Hospital of Shenzhen
        • Contact:
          • Xiaofeng Shi, M.D.
    • Guangxi
      • Nanning, Guangxi, China, 530021
        • Recruiting
        • Guangxi Medical University Cancer Hospital
        • Contact:
          • Ligen Mo, M.D.
    • Hainan
      • Haikou, Hainan, China, 570311
        • Recruiting
        • Hainan General Hospital
        • Contact:
          • Chengpeng Wang, M.D.
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Recruiting
        • The First Affiliated Hospital of Nanjing Medical University
        • Contact:
          • Yongping You, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Individuals aged 18-80 years old with highly suspected (as assessed by study surgeon), newly diagnosed, untreated glioma.
  • Patients without heart insufficiency, lungs insufficiency, renal insufficiency, hepatic insufficiency, autoimmune diseases and other organ diseases with severe dysfunction.
  • Individuals who agree to undergo surgical resection.
  • Individuals with dyskinesia after surgery.
  • All patients giving written informed consent.

Exclusion Criteria:

  • Individuals with age < 18 years or > 80 years.
  • Patients with heart insufficiency, lungs insufficiency, renal insufficiency, hepatic insufficiency, autoimmune diseases and other organ diseases with severe dysfunction.
  • Individuals have acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), have peptic ulcer and gastrointestinal bleeding in the past 5 years.
  • Patients have history of long-term (current) use of anticoagulants, spontaneous intracranial hemorrhage, and venous thromboembolism.
  • Individuals have intracranial hemorrhage after surgery, or other active bleeding.
  • Postoperative coagulation disorders (INR >1.5 or platelet counts < 100x10^9/L).
  • Patients are allergic to Rivaroxaban.
  • Pregnancy or breast-feeding women.
  • Inability to give written informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rivaroxaban group
Patients with highly suspected, newly diagnosed, untreated glioma undergo surgical resection. CT scan within 24 hours after surgery is performed to rule out intracranial hemorrhage and/or infarction. Then those patients with postoperative lower extremity dyskinesia are treated with rivaroxaban (10 mg/day) and compression stockings until 1 month after surgery.
Drug: Rivaroxaban 10 MG
Patients with postoperative lower extremity dyskinesia are treated with rivaroxaban (10 mg/day) and compression stockings until 1 month after surgery.
Other Names:
  • Jiangsu Zhongbang pharmaceutical CO., LTD; Serial numbers: H20203733
Active Comparator: Placebo group
Patients with highly suspected, newly diagnosed, untreated glioma undergo surgical resection. CT scan within 24 hours after surgery is performed to rule out intracranial hemorrhage and/or infarction. Then those patients with postoperative lower extremity dyskinesia are treated with placebo and compression stockings until 1 month after surgery.
Drug: Placebo
Patients with postoperative lower extremity dyskinesia are treated with placebo (10 mg/day) and compression stockings until 1 month after surgery.
Other Names:
  • Jiangsu Zhongbang pharmaceutical CO., LTD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Venous thromboembolism
Time Frame: 6 months
The occurrence of venous thromboembolism, including pulmonary embolism and venous thrombosis of the lower extremities.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fatal hemorrhage
Time Frame: 6 months
Hemoglobin decreases by more than 20 g/L in 24 hours; Intracranial, intraspinal, intraocular, pericardial, retroperitoneal hemorrhage; other life-threatening hemorrhage.
6 months
Non-fatal hemorrhage
Time Frame: 6 months
Wound hematomas, Ecchymosis, gastrointestinal bleeding, hemoptysis, hematuria, epistaxis; other non-fatal hemorrhage.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanfang Hospital, Southern Medical University

Investigators

  • Principal Investigator: Guanglong Huang, M.D., Nanfang Hospital, Southern Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2023

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

February 28, 2025

Study Registration Dates

First Submitted

December 25, 2023

First Submitted That Met QC Criteria

December 25, 2023

First Posted (Actual)

January 9, 2024

Study Record Updates

Last Update Posted (Actual)

January 9, 2024

Last Update Submitted That Met QC Criteria

December 25, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NFEC-2023-314

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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