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

Stroke Clinical Trial

— ERTEMIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05540587
• Other study ID #: KC21MIDS0296
• Status: Recruiting
• Phase: Phase 2
• Start date: May 20, 2022
• Est. completion date: May 20, 2026

Study information

• Verified date: September 2022
• Source: Seoul St. Mary's Hospital
• Contact: Sung hwan Kim, MD, PhD
• Phone: 82-2-2258-6071
• Email: sunghwan[@]catholic.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: May 20, 2026
• Est. primary completion date: May 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 79 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Constriction, Pathologic
• Embolism
• Mitral Valve Stenosis
• Stroke
• Systemic Embolism

Intervention

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)
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Bucheon St. Mary's hospital	Bucheon
Korea, Republic of	Daejeon St. Mary's hospital	Daejeon
Korea, Republic of	Incheon St. Mary's hospital	Incheon
Korea, Republic of	Seoul St. Mary's Hospital	Seoul	Seocho-gu
Korea, Republic of	St. Vincent hospital	Suwon
Korea, Republic of	Uijeongbu St. Mary's Hospital	Uijeongbu
Korea, Republic of	Yeouido St. Mary's hospital	Yeongdeungpo-gu	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Sung-Hwan Kim	Daiichi Sankyo Korea Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

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