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

Primary Purpose

Venous Thromboembolism

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Rivaroxaban
Warfarin
Nadroparin
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Venous Thromboembolism focused on measuring venous thromboembolism, rivaroxaban, vena cava filters

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Anhui Provincial HospitalRecruiting
  • Yantai Yuhuangding HospitalRecruiting
  • Huadong Hospital affiliated to Fudan UniversityRecruiting
  • Shanghai 5th People's HospitalRecruiting
  • Zhongshan Hospital affiliated to Fudan UniversityRecruiting
  • Sir Run Run Shaw HospitalRecruiting
  • The second affiliated hospital of zhejiang university school of medicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Rivaroxaban

Warfarin/ Nadroparin

Arm 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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
August 22, 2019
Last Updated
September 7, 2022
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators
Sir Run Run Shaw Hospital, Huadong Hospital, Shanghai Zhongshan Hospital, Shanghai 5th People's Hospital, Yantai Yuhuangding Hospital, Anhui Provincial Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04066764
Brief Title
Rivaroxaban and Vitamin K Antagonists for the Anticoagulation for the Implantation of Vena Cava Filters
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 8, 2020 (Actual)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators
Sir Run Run Shaw Hospital, Huadong Hospital, Shanghai Zhongshan Hospital, Shanghai 5th People's Hospital, Yantai Yuhuangding Hospital, Anhui Provincial Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism
Keywords
venous thromboembolism, rivaroxaban, vena cava filters

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rivaroxaban
Arm Type
Experimental
Arm 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.
Arm Title
Warfarin/ Nadroparin
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Other Intervention Name(s)
Xarelto
Intervention Description
15mg twice daily for 3 weeks after operation, later 20mg once daily until 3 months after the filter is removed. Application: oral
Intervention Type
Drug
Intervention Name(s)
Warfarin
Other Intervention Name(s)
coumadin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Nadroparin
Other Intervention Name(s)
Fraxiparin
Intervention Description
Dose: 1mg/kg Duration: 5 days after the operation Frequency: twice daily Application: subcutaneous
Primary Outcome Measure Information:
Title
All cause mortality
Description
Percentage of participants with all deaths
Time Frame
4 months after the filter is retrieved
Title
Pulmonary embolism related mortality
Time Frame
4 months after the filter is retrieved
Title
Percentage of Participants with bleeding
Description
Clinically relevant bleeding is defined as a composite of major or clinically relevant nonmajor bleeding
Time Frame
4 months after the filter is retrieved
Title
Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism
Description
the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]
Time Frame
4 months after the filter is retrieved
Secondary Outcome Measure Information:
Title
Percentage of Participants With IVC Filter Retrieval Failure
Description
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.
Time Frame
4 months after the filter is retrieved
Title
Percentage of Participants With an Event for Net Clinical Benefit
Description
composite of primary efficacy outcomes and major bleeding, assessed in the intention-to-treat population.
Time Frame
4 months after the filter is retrieved
Title
Percentage of Participants With Other Vascular Events
Description
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.
Time Frame
4 months after the filter is retrieved

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Li s Yin
Phone
86-0571-87913706
Ext
15268135830
Email
lawson4001@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Zhejie s Liu
Phone
15268135830
Ext
15268135830
Email
lawson3001@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhejie Liu
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Anhui Provincial Hospital
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhengdong Fang, MD
Phone
15256990126
Ext
15256990126
Email
fangzhengdong@126.com
Facility Name
Yantai Yuhuangding Hospital
City
Yantai
State/Province
Shangdong
ZIP/Postal Code
264000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lubin Li, MD
Phone
18653587255
Ext
18653587255
Email
278468192@qq.com
Facility Name
Huadong Hospital affiliated to Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wan Zhang, MD
Phone
13916056910
Ext
13916056910
Email
ant0930@163.com
Facility Name
Shanghai 5th People's Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bin Gao, MD
Phone
13764979078
Ext
13764979078
Email
doctorgaobin@163.com
Facility Name
Zhongshan Hospital affiliated to Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianing Yue, MD
Phone
13564788422
Ext
86
Email
yuejianing@gmail.com
Facility Name
Sir Run Run Shaw Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuefeng R Zhu, MD
Phone
13868101010
Ext
13868101010
Email
drzyf@hotmail.com
Facility Name
The second affiliated hospital of zhejiang university school of medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhejie Liu, MD,PhD
Phone
15268135830
Ext
86
Email
lawson3001@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Study protocol, statistical analysis plan and informed consent form will be openly available.
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Rivaroxaban and Vitamin K Antagonists for the Anticoagulation for the Implantation of Vena Cava Filters

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