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

• ClinicalTrials.gov Identifier: NCT03244319
• Recruitment Status: Completed
• First Posted: August 9, 2017
• Last Update Posted: January 2, 2020
• Sponsor: Yonsei University
• Information provided by (Responsible Party): Yonsei University

Study Description

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

Condition or disease	Intervention/treatment	Phase
MV(Mitral Valve) Repair	Drug: Edoxaban; Drug: Warfarin; Drug: parenteral anti-coagulant (UFH)	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Explore the Efficacy and Safety of edoxabaN in Patients After Heart Valve Repair or Bioprosthetic vaLve Replacement (ENAVLE Trial)
• Actual Study Start Date: December 1, 2017
• Actual Primary Completion Date: September 30, 2019
• Actual Study Completion Date: September 30, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Edoxaban	Drug: 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).
Active Comparator: Warfarin	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.; Drug: parenteral anti-coagulant (UFH); parenteral anti-coagulant (UFH)

Outcome Measures

Primary Outcome Measures :

1. Occurrence of thromboembolic event [ Time Frame: 12 weeks ]
   Occurrence of thromboembolic events and any thrombus at repaired ring or bioprosthetic valves detected by follow up echocardiography or 3D CT scan

Secondary Outcome Measures :

1. Dysfunction of treated valve [ Time Frame: 12 weeks ]
   Dysfunction of treated valve caused by thrombosis on echocardiography or 3D CT scan

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Korea, Republic of

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

Seoul, Korea, Republic of, 03722

Sponsors and Collaborators

Yonsei University

More Information

• Responsible Party: Yonsei University
• ClinicalTrials.gov Identifier: NCT03244319
• Other Study ID Numbers: 4-2017-0506
• First Posted: August 9, 2017
• Last Update Posted: January 2, 2020
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Warfarin; Edoxaban; Anticoagulants; Coagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action