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

Venous Thromboembolism Clinical Trial

— EPICT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04066764
• Other study ID #: SAHZhejiangU-002
• Status: Recruiting
• Phase: Phase 3
• Start date: May 8, 2020
• Est. completion date: October 1, 2024

Study information

• Verified date: April 2024
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Li s Yin
• Phone: 86-0571-87913706
• Email: lawson4001[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: October 1, 2024
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Rivaroxaban
15mg twice daily for 3 weeks after operation, later 20mg once daily until 3 months after the filter is removed. Application: oral
• Warfarin
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
• Nadroparin
Dose: 1mg/kg Duration: 5 days after the operation Frequency: twice daily Application: subcutaneous

Locations

Country	Name	City	State
China	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	The second affiliated hospital of zhejiang university school of medicine	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Huadong Hospital affiliated to Fudan University	Shanghai	Shanghai
China	Shanghai 5th People's Hospital	Shanghai	Shanghai
China	Zhongshan Hospital affiliated to Fudan University	Shanghai	Shanghai
China	Yantai Yuhuangding Hospital	Yantai	Shangdong

Sponsors (7)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University	Anhui Provincial Hospital, Huadong Hospital, Shanghai 5th People's Hospital, Shanghai Zhongshan Hospital, Sir Run Run Shaw Hospital, Yantai Yuhuangding Hospital

Country where clinical trial is conducted

China, 

References & Publications (9)

Breddin HK, Hach-Wunderle V, Nakov R, Kakkar VV; CORTES Investigators. Clivarin: Assessment of Regression of Thrombosis, Efficacy, and Safety. Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis. N Engl J Med. 2001 Mar 1;344(9):626-31. doi: 10.1056/NEJM200103013440902. — View Citation

EINSTEIN Investigators; Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. doi: 10.1056/NEJMoa1007903. Epub 2010 Dec 3. — View Citation

EINSTEIN-PE Investigators; Buller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. doi: 10.1056/NEJMoa1113572. Epub 2012 Mar 26. — View Citation

Jain A, Cifu AS. Antithrombotic Therapy for Venous Thromboembolic Disease. JAMA. 2017 May 16;317(19):2008-2009. doi: 10.1001/jama.2017.1928. No abstract available. — View Citation

Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JRE, Wells P, Woller SC, Moores L. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315-352. doi: 10.1016/j.chest.2015.11.026. Epub 2016 Jan 7. Erratum In: Chest. 2016 Oct;150(4):988. — View Citation

Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. doi: 10.1056/NEJMoa076016. — View Citation

Prins MH, Lensing AW, Brighton TA, Lyons RM, Rehm J, Trajanovic M, Davidson BL, Beyer-Westendorf J, Pap AF, Berkowitz SD, Cohen AT, Kovacs MJ, Wells PS, Prandoni P. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol. 2014 Oct;1(1):e37-46. doi: 10.1016/S2352-3026(14)70018-3. Epub 2014 Sep 28. — View Citation

Schulman S, Zondag M, Linkins L, Pasca S, Cheung YW, de Sancho M, Gallus A, Lecumberri R, Molnar S, Ageno W, Le Gal G, Falanga A, Hulegardh E, Ranta S, Kamphuisen P, Debourdeau P, Rigamonti V, Ortel TL, Lee A. Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis. J Thromb Haemost. 2015 Jun;13(6):1010-8. doi: 10.1111/jth.12955. Epub 2015 May 9. — View Citation

Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. doi: 10.1016/S0140-6736(09)60734-0. Epub 2009 May 4. Erratum In: Lancet. 2022 Dec 10;400(10368):2048. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All cause mortality	Percentage of participants with all deaths	4 months after the filter is retrieved
Primary	Pulmonary embolism related mortality		4 months after the filter is retrieved
Primary	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
Primary	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	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
Secondary	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
Secondary	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