Efficacy and Safety of Edoxaban in Patients With Atrial Fibrillation and Mitral Stenosis

NCT ID: NCT05540587

Last Updated: 2022-09-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-20
• Study Completion Date: 2026-05-20

Brief Summary

This study aims to compare the efficacy and safety of the edoxaban and the warfarin in atrial fibrillation patients with mitral stenosis.

The study design is a multicenter, randomized, open-label, investigator initiated phase 2 trial. The patients were randomly assigned to Edoxaban or Warfarin groups. Primary outcome was a composite of stroke and systemic arterial thromboembolism. The safety outcome was major bleeding.

Detailed Description

Non-vitamin K antagonist oral anticoagulants (NOACs) are generally recommended as 1st line therapy for oral anticoagulant in patients with atrial fibrillation (AF). But, the efficacy and safety of NOAC in AF patients with prosthetic mechanical heart valves or moderate to severe mitral valve stenosis have not been proven, and the guidelines recommend vitamin K antagonist (VKA) administration to those patient groups. This trial aims to compare the efficacy and safety of the edoxaban and the warfarin in AF patients with moderate to severe mitral valve stenosis.

Edoxaban in patients with aTrial fibrillation and MItral Stenosis (ERTEMIS) trial is a multicenter, randomized, open-label, investigator initiated phase 2 trial. The patients were randomly assigned to Edoxaban or Warfarin groups. The primary efficacy outcome is a composite of stroke and systemic arterial thromboembolism. The secondary efficacy outcomes are each component of the primary efficacy outcomes and death from any cause. The safety outcome was major bleeding.

Conditions

Mitral Valve Stenosis; Atrial Fibrillation; Stroke; Systemic Embolism

Study Design

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

Study Groups

Edoxaban

Patients in the Edoxaban group take Edoxaban 60mg once daily. If any of the following conditions are present, take 30mg once daily.

• CrCl 15-50mL/min
• Body weight ≤ 60kg
• Concomitant use of P-glycoprotein inhibitor (Dronearone, Ciclosporine, Erythromycin or Ketoconazole)

Group Type: EXPERIMENTAL

Edoxaban

Intervention Type: DRUG

Patients in the Edoxaban group take Edoxaban 60mg once daily. If any of the following conditions are present, take 30mg once daily.

• CrCl 15-50mL/min
• Body weight ≤ 60kg
• Concomitant use of P-glycoprotein inhibitor (Dronearone, Ciclosporine, Erythromycin or Ketoconazole)

Warfarin

Patients in the Warfarin group take Warfarin 2-10mg once daily, dose adjusted with the target INR 2-3. In the elderly or frail patients, a lower dose administration is allowed at the discretion of the investigator.

Group Type: ACTIVE_COMPARATOR

Warfarin

Intervention Type: DRUG

Patients in the Warfarin group take Warfarin 2-10mg once daily, dose adjusted with the target INR 2-3. In the elderly or frail patients, a lower dose administration is allowed at the discretion of the investigator.

Interventions

Edoxaban

Patients in the Edoxaban group take Edoxaban 60mg once daily. If any of the following conditions are present, take 30mg once daily.

• CrCl 15-50mL/min
• Body weight ≤ 60kg
• Concomitant use of P-glycoprotein inhibitor (Dronearone, Ciclosporine, Erythromycin or Ketoconazole)

Intervention Type: DRUG

Warfarin

Patients in the Warfarin group take Warfarin 2-10mg once daily, dose adjusted with the target INR 2-3. In the elderly or frail patients, a lower dose administration is allowed at the discretion of the investigator.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18 < Age < 80
• AF diagnosed by ECG at any time prior to enrollment
• Moderate or severe mitral valve stenosis diagnosed by echocardiography at any time prior to enrollment

Exclusion Criteria

• Refusal to consent
• Transient AF due to reversible cause (Postoperative, ongoing systemic inflammation, thyrotoxicosis)
• Patients undergoing mechanical valve replacement
• Coagulopathy
• Hepatic impairment with significant bleeding risk
• High bleeding risk due to following disease or condition diagnosed within 1 month prior to randomization

• GI ulcer or bleeding, Esophageal or gastric varix, Malignancy, Brain or cord injury, Surgery for brain, spinal cord, opthalmic, Intracranial hemorrhage, Arteriovenous malformation, Vascular aneurysms, Brain or spinal vascular disorder
• Stroke, Systemic arterial thromboembolism, Acute myocardial infarction diagnosed within 14 days prior to randomization
• End stage kidney disease (CrCL < 15mL/min) or Dialysis
• Severe hypertension
• Alcohol abuse or other psychiatric disease
• Epidural puncture or anesthesia
• Pulmonary thromboembolism with hemodynamical instability requiring thrombolysis or thrombectomy
• Pregnant or lactating women
• Allergy to edoxaban or warfarin
• Ongoing need for other anticoagulant or clarithromycin, rifampin)
• Participants for other trials within 1 month prior to enrollment
• Other patients to be inappropriate to participate in the trial determined by the investigator

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo Korea Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Sung-Hwan Kim

OTHER

Sponsor Role: lead

Responsible Party

Sung-Hwan Kim

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Seoul St. Mary's Hospital

Seoul, Seocho-gu, South Korea

Site Status: RECRUITING

Yeouido St. Mary's hospital

Yeongdeungpo-gu, Seoul, South Korea

Site Status: RECRUITING

Bucheon St. Mary's hospital

Bucheon-si, , South Korea

Site Status: RECRUITING

Daejeon St. Mary's hospital

Daejeon, , South Korea

Site Status: RECRUITING

Incheon St. Mary's hospital

Incheon, , South Korea

Site Status: RECRUITING

St. Vincent hospital

Suwon, , South Korea

Site Status: RECRUITING

Uijeongbu St. Mary's Hospital

Uijeongbu-si, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Sung hwan Kim, MD, PhD

Role: CONTACT

sunghwan@catholic.ac.kr

82-2-2258-6071

Facility Contacts

Sung Hwan Kim, MD

Role: primary

sunghwan@catholic.ac.kr

82-2-2258-6071

Young Kyoung Sa, MD

Role: primary

Chan seok Park, MD

Role: primary

Jung Sun Cho, MD

Role: primary

Mi Jung Kim, MD

Role: primary

You Mi Hwang, MD

Role: primary

Hyo suk Ahn, MD

Role: primary

Other Identifiers

KC21MIDS0296

Identifier Type: -

Identifier Source: org_study_id