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

Zhejiang University

Status and phase: Enrolling; Phase 3

Conditions: Venous Thromboembolism

Treatments: Drug: Warfarin; Drug: Nadroparin; Drug: Rivaroxaban

Study type: Interventional

Funder types: Other

Identifiers

NCT04066764

SAHZhejiangU-002

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Rivaroxaban

Experimental group

Description:

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.

Treatment:

Drug: Rivaroxaban

Warfarin/ Nadroparin

Active Comparator group

Description:

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.

Treatment:

Drug: Nadroparin

Drug: Warfarin