Rivaroxaban and Vitamin K Antagonists for the Anticoagulation for the Implantation of Vena Cava Filters

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of new oral anticoagulants and vitamin K antagonists for the anticoagulation for the implantation of vena cava filters in patients with deep venous thrombosis.

Detailed Description
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Deep vein thrombosis (DVT) of lower extremities is a venous reflux disorder caused by abnormal coagulation of deep vein blood. The main adverse consequences of DVT are pulmonary embolism (PE) and post-thrombotic syndrome, which can significantly affect the quality of life of patients and even lead to death. Anticoagulation is the basic treatment of DVT, which can inhibit the spread of thrombus, facilitate thrombus autolysis and recanalization of the lumen, and reduce the incidence and mortality of PE. For patients with contraindications or complications of anticoagulation therapy, the implantation of inferior vena cava filter may be considered. At the same time, patients with the following conditions may be considered for the implantation of inferior vena cava filter: PE is still present in the case of adequate anticoagulant therapy, floating thrombus in the iliac, femoral or inferior vena cava, thrombectomy is planned for acute DVT, and abdominal, pelvic or lower extremity surgery with high risk factors for PE and acute DVT. The current standard treatment regimen for venous thromboembolism (VTE) anticoagulation is low molecular weight heparin (LMWH) combined with or followed by vitamin K antagonist warfarin. It has been proved that low molecular weight heparin has good safety and effectiveness in the prevention and initial treatment of VTE, especially for VTE prevention and treatment in cancer patients and pregnant patients. As a standard oral anticoagulant, warfarin has definite anticoagulant effect and is cheap. However, low molecular weight heparin needs subcutaneous injection, which can cause adverse reactions such as pain, itching, subcutaneous hemorrhage and nodules at the injection site, and some complications such as heparin-induced thrombocytopenia (HIT). Warfarin anticoagulation therapy requires long-term laboratory monitoring of international standardized ratio (INR) and timely adjustment of warfarin dosage according to INR, which will result in difficult follow-up management, poor compliance, uncertainty of warfarin treatment effect, and even serious bleeding complications. According to relevant studies, the incidence of warfarin-related major bleeding is about 1%-2%, and the recurrence or aggravation of thrombus is also high. Rivaroxaban can simplify treatment, and is safe. It's also not easy to interact with food or drugs. Previous studies have shown that rivaroxaban is effective in preventing deep venous thrombosis after orthopaedic surgery. Rivaroxaban has also been shown to be safe and effective in anticoagulation therapy for patients with deep venous thrombosis and pulmonary embolism, and repeated coagulation monitoring is not required. However, Rivaroxaban lacks sufficient clinical data for perioperative adjuvant anticoagulation therapy of filter implantation. Therefore, this study should be carried out to provide the basis for DVT treatment guidelines and explore the clinical indications of rivaroxaban.

Official Title
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An Efficacy and Safety Study of New Oral Anticoagulants and Vitamin K Antagonists for the Anticoagulation for the Implantation of Vena Cava Filters: A Prospective Randomized Controlled Trial

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Rivaroxaban
* Drug: Warfarin
* Drug: Nadroparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who was diagnosed with deep venous thrombosis of the lower extremity and implanted with a retrievable inferior vena cava filter. Exclusion Criteria: Age < 18 years or age > 75 years, With obvious contraindications for anticoagulation therapy, Allergic to iodine contrast agents in the past, Pregnant or breastfeeding women, With malignant tumors and life expectancy < 1 year, Severe liver diseases (such as acute hepatitis, chronic active hepatitis or cirrhosis) or alanine aminotransferase levels were higher than three times the upper limit of normal. With other diseases that need anticoagulation, With previous heparin-induced thrombocytopenia, Bacterial endocarditis, Systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg, Taking cytochrome P450 3A4(CYP-450 3A4) inhibitors or inducers With severe renal insufficiency (creatinine clearance <30 mL/min) Allergic to the drug used in this study With permanent filter implantation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban<br>Participants will receive rivaroxaban 15mg oral twice daily for 3 weeks after operation, later rivaroxaban 20mg oral once daily until 3 months after the filter is retrieved. | Drug: Rivaroxaban<br>* 15mg twice daily for 3 weeks after operation, later 20mg once daily until 3 months after the filter is removed. Application: oral<br>* Other names: Xarelto;|
| Active Comparator: Warfarin/ Nadroparin<br>Participants will receive Nadroparin 1mg/kg twice daily (subcutaneous), plus warfarin 3mg oral once daily for 5 days after the operation, later warfarin(oral) at individually titrated doses(0.75mg to 18mg) to achieve a target international normalized ratio (INR) of 2.0 to 3.0, once daily until 3 months after the filter is retrieved. | Drug: Warfarin<br>* 3mg for 5 days after the operation, later 0.75mg to 18mg depending on INR (2.0-3.0) until until 3 months after the filter is removed. Frequency: once daily Application: oral<br>* Other names: coumadin;Drug: Nadroparin<br>* Dose: 1mg/kg Duration: 5 days after the operation Frequency: twice daily Application: subcutaneous<br>* Other names: Fraxiparin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | Percentage of participants with all deaths | 4 months after the filter is retrieved | 
| Pulmonary embolism related mortality |  | 4 months after the filter is retrieved | 
| Percentage of Participants with bleeding | Clinically relevant bleeding is defined as a composite of major or clinically relevant nonmajor bleeding | 4 months after the filter is retrieved | 
| Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism | the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE] | 4 months after the filter is retrieved | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With IVC Filter Retrieval Failure | IVC filter retrieval failure is relevant to IVC filter complications (e.g. IVC thrombosis, IVC perforation, IVC filter migration or tilting and IVC filter embolization), system factors and technical factors. | 4 months after the filter is retrieved | 
| Percentage of Participants With an Event for Net Clinical Benefit | composite of primary efficacy outcomes and major bleeding, assessed in the intention-to-treat population. | 4 months after the filter is retrieved | 
| Percentage of Participants With Other Vascular Events | All pre-defined vascular events (ST segment elevation myocardial infarction, non ST segment elevation myocardial infarction, acute coronary syndrome, unstable angina, ischemic stroke, transient ischemic attack, pulmonary embolism, non-central nervous system systemic embolism or vascular death) will be assessed based results/films/images of confirmatory testing, and/or case summaries. | 4 months after the filter is retrieved | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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venous thromboembolism, rivaroxaban, vena cava filters