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

• Sponsor: Sung-Hwan Kim (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05540587
• Collaborator: Daiichi Sankyo Korea Co., Ltd. (Industry)
• Enrollment: 240
• Locations: 7
• Arms: 2
• Anticipated Duration (Months): 48
• Patients Per Site: 34.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mitral Valve Stenosis; Atrial Fibrillation; Stroke; Systemic Embolism	Drug: Edoxaban; Drug: Warfarin	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open, Phase 2 Study to Evaluate the Efficacy and Safety of Edoxaban in Patients With Atrial Fibrillation and Mitral Stenosis
• Actual Study Start Date: May 20, 2022
• Anticipated Primary Completion Date: May 20, 2024
• Anticipated Study Completion Date: May 20, 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Composite of Stroke or Systemic arterial thromboembolism [15 days after randomization]

   The number of patients with the first occurrence of a stroke or systemic embolism during the study period

Secondary Outcome Measures

1. Stroke [15 days after randomization]

   The number of patients with the first occurrence of a stroke during the study period

2. Systemic embolism [15 days after randomization]

   The number of patients with the first occurrence of a systemic embolism during the study period

3. Death from any cause [15 days after randomization]

   The number of patients who died for any reason during the study period

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul St. Mary's Hospital	Seoul	Seocho-gu	Korea, Republic of	06591
2	Yeouido St. Mary's hospital	Yeongdeungpo-gu	Seoul	Korea, Republic of	07345
3	Bucheon St. Mary's hospital	Bucheon		Korea, Republic of	14647
4	Daejeon St. Mary's hospital	Daejeon		Korea, Republic of	34943
5	Incheon St. Mary's hospital	Incheon		Korea, Republic of	21431
6	St. Vincent hospital	Suwon		Korea, Republic of	16247
7	Uijeongbu St. Mary's Hospital	Uijeongbu		Korea, Republic of	11765

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sung-Hwan Kim, Professor, Seoul St. Mary's Hospital
• ClinicalTrials.gov Identifier: NCT05540587
• Other Study ID Numbers: KC21MIDS0296
• First Posted: Sep 14, 2022
• Last Update Posted: Sep 14, 2022
• Last Verified: Sep 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sung-Hwan Kim, Professor, Seoul St. Mary's Hospital: Edoxaban; Warfarin; Stroke; Systemic embolism; Mitral Valve Stenosis; Atrial Fibrillation
• Additional relevant MeSH terms: Atrial Fibrillation; Embolism; Mitral Valve Stenosis; Constriction, Pathologic; Warfarin; Edoxaban

Study Results

No Results Posted as of Sep 14, 2022