Trial Title:
Efficacy and Safety of Rivaroxaban in the Prevention of Venous Thromboembolism in Glioma Patients
NCT ID:
NCT06196918
Condition:
Glioma, Malignant
Conditions: Official terms:
Glioma
Thromboembolism
Venous Thromboembolism
Rivaroxaban
Conditions: Keywords:
Glioma
Rivaroxaban
Venous Thromboembolism
Dyskinesia
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Prevention
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Rivaroxaban 10 MG
Description:
Patients with postoperative lower extremity dyskinesia are treated with rivaroxaban (10
mg/day) and compression stockings until 1 month after surgery.
Arm group label:
Rivaroxaban group
Other name:
Jiangsu Zhongbang pharmaceutical CO., LTD; Serial numbers: H20203733
Intervention type:
Drug
Intervention name:
Placebo
Description:
Patients with postoperative lower extremity dyskinesia are treated with placebo (10
mg/day) and compression stockings until 1 month after surgery.
Arm group label:
Placebo group
Other name:
Jiangsu Zhongbang pharmaceutical CO., LTD
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.
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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Tiantan Hospital
Address:
City:
Beijing
Zip:
100070
Country:
China
Status:
Recruiting
Contact:
Last name:
Lei Wang, M.D.
Facility:
Name:
Fujian provincial hospital
Address:
City:
Fuzhou
Zip:
350001
Country:
China
Status:
Recruiting
Contact:
Last name:
Shihao Zheng, M.D.
Facility:
Name:
The First People's Hospital of Foshan
Address:
City:
Foshan
Zip:
528000
Country:
China
Status:
Recruiting
Contact:
Last name:
Lianxu Cui, M.D.
Facility:
Name:
The First Affiliated Hospital of Shantou University Medical College
Address:
City:
Shantou
Zip:
515041
Country:
China
Status:
Recruiting
Contact:
Last name:
Yiming Xu, M.D.
Facility:
Name:
Longgang Central Hospital of Shenzhen
Address:
City:
Shenzhen
Zip:
518116
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiaofeng Shi, M.D.
Facility:
Name:
Guangxi Medical University Cancer Hospital
Address:
City:
Nanning
Zip:
530021
Country:
China
Status:
Recruiting
Contact:
Last name:
Ligen Mo, M.D.
Facility:
Name:
Hainan general hospital
Address:
City:
Haikou
Zip:
570311
Country:
China
Status:
Recruiting
Contact:
Last name:
Chengpeng Wang, M.D.
Facility:
Name:
The First Affiliated Hospital of Nanjing Medical University
Address:
City:
Nanjing
Zip:
210029
Country:
China
Status:
Recruiting
Contact:
Last name:
Yongping You, M.D.
Start date:
November 1, 2023
Completion date:
February 28, 2025
Lead sponsor:
Agency:
Nanfang Hospital, Southern Medical University
Agency class:
Other
Source:
Nanfang Hospital, Southern Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06196918
