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

Glioma, Malignant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06196918
• Other study ID #: NFEC-2023-314
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: February 28, 2025

Study information

• Verified date: December 2023
• Source: Nanfang Hospital, Southern Medical University
• Contact: Tianshi Que, M.D.
• Phone: +86-020-61641806
• Email: qtssjwk[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: February 28, 2025
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glioma
• Glioma, Malignant
• Thromboembolism
• Venous Thromboembolism

Intervention

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

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital	Beijing	Beijing
China	The First People's Hospital of Foshan	Foshan	Guangdong
China	Fujian provincial hospital	Fuzhou	Fujian
China	Hainan general hospital	Haikou	Hainan
China	The First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Guangxi Medical University Cancer Hospital	Nanning	Guangxi
China	The First Affiliated Hospital of Shantou University Medical College	Shantou	Guangdong
China	Longgang Central Hospital of Shenzhen	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital, Southern Medical University

Country where clinical trial is conducted

China, 

References & Publications (17)

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Mohamed MFH, ElShafei MN, Ahmed MB, Abdalla LO, Ahmed I, Elzouki AN, Danjuma MI. The Net Clinical Benefit of Rivaroxaban Compared to Low-Molecular-Weight Heparin in the Treatment of Cancer-Associated Thrombosis: Systematic Review and Meta-Analysis. Clin Appl Thromb Hemost. 2021 Jan-Dec;27:1076029620940046. doi: 10.1177/1076029620940046. — View Citation

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* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Venous thromboembolism	The occurrence of venous thromboembolism, including pulmonary embolism and venous thrombosis of the lower extremities.	6 months
Secondary	Fatal hemorrhage	Hemoglobin decreases by more than 20 g/L in 24 hours; Intracranial, intraspinal, intraocular, pericardial, retroperitoneal hemorrhage; other life-threatening hemorrhage.	6 months
Secondary	Non-fatal hemorrhage	Wound hematomas, Ecchymosis, gastrointestinal bleeding, hemoptysis, hematuria, epistaxis; other non-fatal hemorrhage.	6 months