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

Sung-Hwan Kim

Status and phase: Enrolling; Phase 2

Conditions: Atrial Fibrillation; Stroke; Mitral Valve Stenosis; Systemic Embolism

Treatments: Drug: Edoxaban; Drug: Warfarin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05540587

KC21MIDS0296

Details and patient eligibility

About

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.

Full 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.

Enrollment: 240 estimated patients

Sex: All

Ages: 19 to 79 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

Edoxaban

Experimental group

Description:

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)

Treatment:

Drug: Edoxaban

Warfarin

Active Comparator group

Description:

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.

Treatment:

Drug: Warfarin