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

A Randomized, Open, Phase 2 Study to Evaluate the Efficacy and Safety of Edoxaban in Patients With Atrial Fibrillation and Mitral Stenosis

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Atrial Fibrillation; Mitral Valve Stenosis; Systemic Embolism
• Intervention / Treatment: Drug: Edoxaban; Drug: Warfarin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sung hwan Kim, MD, PhD; Phone Number: 82-2-2258-6071; Email: sunghwan@catholic.ac.kr

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of, 14647
    • Recruiting
    • Bucheon St. Mary's Hospital
    • Contact: Chan seok Park, MD
  • Daejeon, Korea, Republic of, 34943
    • Recruiting
    • Daejeon St. Mary's hospital
    • Contact: Jung Sun Cho, MD
  • Incheon, Korea, Republic of, 21431
    • Recruiting
    • Incheon St. Mary's Hospital
    • Contact: Mi Jung Kim, MD
  • Suwon, Korea, Republic of, 16247
    • Recruiting
    • St. Vincent Hospital
    • Contact: You Mi Hwang, MD
  • Uijeongbu, Korea, Republic of, 11765
    • Recruiting
    • Uijeongbu St. Mary's Hospital
    • Contact: Hyo suk Ahn, MD
  • Seocho-gu
    • Seoul, Seocho-gu, Korea, Republic of, 06591
      • Recruiting
      • Seoul St. Mary's Hospital
      • Contact: Sung Hwan Kim, MD; Phone Number: 82-2-2258-6071; Email: sunghwan@catholic.ac.kr
      • Sub-Investigator: Ju Youn Kim, MD
      • Sub-Investigator: Hwa Jung Kim, MD
  • Seoul
    • Yeongdeungpo-gu, Seoul, Korea, Republic of, 07345
      • Recruiting
      • Yeouido St. Mary's Hospital
      • Contact: Young Kyoung Sa, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: 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)
Active Comparator: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of Stroke or Systemic arterial thromboembolism	The number of patients with the first occurrence of a stroke or systemic embolism during the study period	15 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke	The number of patients with the first occurrence of a stroke during the study period	15 days after randomization
Systemic embolism	The number of patients with the first occurrence of a systemic embolism during the study period	15 days after randomization
Death from any cause	The number of patients who died for any reason during the study period	15 days after randomization

Collaborators and Investigators

• Sponsor: Sung-Hwan Kim
• Collaborators: Daiichi Sankyo Korea Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2022
• Primary Completion (Anticipated): May 20, 2024
• Study Completion (Anticipated): May 20, 2026

Study Registration Dates

• First Submitted: September 12, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Stroke; Atrial Fibrillation; Warfarin; Systemic embolism; Edoxaban; Mitral Valve Stenosis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Pathological Conditions, Anatomical; Arrhythmias, Cardiac; Heart Valve Diseases; Embolism; Atrial Fibrillation; Constriction, Pathologic; Mitral Valve Stenosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban; Warfarin
• Other Study ID Numbers: KC21MIDS0296

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No