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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 80 Years
Gender All
More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06196918
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Nanfang Hospital, Southern Medical University
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Guanglong Huang, M.D.
Principal Investigator Affiliation Nanfang Hospital, Southern Medical University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioma, Malignant
Additional Details

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.

Arms & Interventions

Arms

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.

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.

Interventions

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.

Drug: - Placebo

Patients with postoperative lower extremity dyskinesia are treated with placebo (10 mg/day) and compression stockings until 1 month after surgery.

Contact a Trial Team

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International Sites

Beijing Tiantan Hospital, Beijing, Beijing, China

Status

Recruiting

Address

Beijing Tiantan Hospital

Beijing, Beijing, 100070

Site Contact

Lei Wang, M.D.

[email protected]

+86-020-61641806

Fujian provincial hospital, Fuzhou, Fujian, China

Status

Recruiting

Address

Fujian provincial hospital

Fuzhou, Fujian, 350001

Site Contact

Shihao Zheng, M.D.

[email protected]

+86-020-61641806

The First People's Hospital of Foshan, Foshan, Guangdong, China

Status

Recruiting

Address

The First People's Hospital of Foshan

Foshan, Guangdong, 528000

Site Contact

Lianxu Cui, M.D.

[email protected]

+86-020-61641806

Shantou, Guangdong, China

Status

Recruiting

Address

The First Affiliated Hospital of Shantou University Medical College

Shantou, Guangdong, 515041

Site Contact

Yiming Xu, M.D.

[email protected]

+86-020-61641806

Longgang Central Hospital of Shenzhen, Shenzhen, Guangdong, China

Status

Recruiting

Address

Longgang Central Hospital of Shenzhen

Shenzhen, Guangdong, 518116

Site Contact

Xiaofeng Shi, M.D.

[email protected]

+86-020-61641806

Nanning, Guangxi, China

Status

Recruiting

Address

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, 530021

Site Contact

Ligen Mo, M.D.

[email protected]

+86-020-61641806

Hainan general hospital, Haikou, Hainan, China

Status

Recruiting

Address

Hainan general hospital

Haikou, Hainan, 570311

Site Contact

Chengpeng Wang, M.D.

[email protected]

+86-020-61641806

Nanjing, Jiangsu, China

Status

Recruiting

Address

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029

Site Contact

Yongping You, M.D.

[email protected]

+86-020-61641806

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