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

Yonsei University

Status and phase

Completed

Phase 3

Conditions

MV(Mitral Valve) Repair

Treatments

Drug: Edoxaban

Drug: Warfarin

Drug: parenteral anti-coagulant (UFH)

Study type

Interventional

Funder types

Other

Identifiers

NCT03244319

4-2017-0506

Details and patient eligibility

About

objectives: The primary aim of ENAVLE is to explore the efficacy of edoxaban in patients with post mitral valve repair or bioprosthetic valve implantation
Primary / Secondary Endpoint

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
Safety Endpoint Evaluation

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

Full 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.

Enrollment

220 patients

Sex

All

Ages

20 to 85 years old

Volunteers

No Healthy Volunteers

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