Explore the Efficacy and Safety of edoxabaN in Patients After Heart Valve Repair or Bioprosthetic vaLve Replacement (ENAVLE Trial)

NCT ID: NCT03244319

Last Updated: 2020-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2019-09-30

Brief Summary

1. objectives: The primary aim of ENAVLE is to explore the efficacy of edoxaban in patients with post mitral valve repair or bioprosthetic valve implantation

2. Primary / Secondary Endpoint

1) Efficacy Endpoint Evaluation: Occurrence of thromboembolic events and any thrombus at repaired ring or bioprosthetic valves detected by follow up echocardiography or 3D CT scan

2) Safety Endpoint Evaluation

• Dysfunction of treated valve caused by thrombosis on echocardiography or 3D CT scan
• Major or minor bleeding described in safety outcomes

Detailed Description

This study is an open labeled, parallel group, and randomization study. At 7 days after mitral valve repair, bioprosthetic MV or AV replacement surgery, warfarin or edoxaban will be started per oral route. All study patients started to receive bridging therapy with parenteral anti-coagulant (UFH) according to local practice before switching to warfarin or edoxaban. Among patients who take warfarin, international normalized ratio will be used to monitor the effectiveness of the anticoagulant warfarin as usual daily practice. All patients who are assigned to VKA group, bridging with warfarin and UFH is mandatory until INR reach therapeutic target range (INR 2-3). Warfarin dose will be adjusted for maintain therapeutic range (INR 2-3) during follow up period. Patients who are randomly assigned to edoxaban group will be received 60mg qd or 30mg qd ( creatinine clearance 30-49ml/min, body weight <60kg or concomitant use of certain P-glycoprotein inhibitors). Both drugs will be maintained for 3 months. During study period, all patients will be carefully monitored for thromboembolic events including valve dysfunction, and stroke or bleeding complication. At 3 months after surgery, 3 dimensional CT scan and echocardiography will be performed for detecting valvular dysfunction, any thrombus or bleeding in heart & lung.

Conditions

MV(Mitral Valve) Repair

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Edoxaban

Group Type: EXPERIMENTAL

Edoxaban

Intervention Type: DRUG

Patients who are randomly assigned to edoxaban group will be received 60mg qd or 30mg qd (creatinine clearance 30-49ml/min, body weight \<60kg or concomitant use of certain P-glycoprotein inhibitors).

Warfarin

Group Type: ACTIVE_COMPARATOR

Warfarin

Intervention Type: DRUG

All patients who are assigned to VKA group, bridging with warfarin and UFH is mandatory until INR reach therapeutic target range (INR 2-3). Warfarin dose will be adjusted for maintain therapeutic range (INR 2-3) during follow up period.

parenteral anti-coagulant (UFH)

Intervention Type: DRUG

parenteral anti-coagulant (UFH)

Interventions

Edoxaban

Patients who are randomly assigned to edoxaban group will be received 60mg qd or 30mg qd (creatinine clearance 30-49ml/min, body weight \<60kg or concomitant use of certain P-glycoprotein inhibitors).

Intervention Type: DRUG

Warfarin

All patients who are assigned to VKA group, bridging with warfarin and UFH is mandatory until INR reach therapeutic target range (INR 2-3). Warfarin dose will be adjusted for maintain therapeutic range (INR 2-3) during follow up period.

Intervention Type: DRUG

parenteral anti-coagulant (UFH)

parenteral anti-coagulant (UFH)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients aged 20-85 years with
• MV repair or Bioprosthetic MV or AV replacement
• Patients with written informed consent

Exclusion Criteria

• Previous mechanical prosthetic heart valve replacement
• Patients who underwent TAVI
• Concomitant bioprosthetic valve replacement of mechanical tricuspid or pulmonary replacement at the time of the index valve replacement surgery
• Clinically relevant paravalvular leaks
• Previous history of endocarditis
• Complex congenital heart abnormality
• Acute coronary syndrome within one month
• Uncontrolled hypertension
• Previous history of hemorrhagic stroke
• At high risk for bleeding
• Active hepatitis or liver dysfunction (AST/ALT> 3times of upper normal limits)
• Creatinine clearance < 30ml/min
• Patients with a clear indication for long-term dual antiplatelet therapy
• Malignancy or radiation therapy within one month
• Treatment with selected drugs that my interact with edoxaban (specific P-gp inhibitors, ie. verapamil, quinidine; the short-term use of azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole)
• At of pregnancy or breastfeeding
• Known allergy to warfarin or edoxaban

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine

Seoul, , South Korea

Countries

South Korea

Other Identifiers

4-2017-0506

Identifier Type: -

Identifier Source: org_study_id