STroke Secondary Prevention With Catheter ABLation and EDoxaban for Patients With Non-valvular Atrial Fibrillation: STABLED Study (STABLED)

Catheter ablation (CA) has been reported to reduce risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) in retrospective studies, but risk and benefit of CA has not been well elucidated in NVAF with recent cerebral infarction in prospective randomized trials.

Study Overview

• Status: Active, not recruiting
• Conditions: Ischemic Stroke; Atrial Fibrillation Non-Rheumatic
• Intervention / Treatment: Procedure: Catheter ablation

Detailed Description

In patients with NVAF, stroke is an independent risk factor for a subsequent cerebral infarction. Although anticoagulant therapy can effectively reduce thromboembolic events, the reported annual recurrence rate in NVAF and previous stroke patients in the "real-world" is not low even with appropriate antithrombotic treatment; 8.6% in patients with "guideline adherent" antithrombotic therapy and around 5% in patients treated with anticoagulant therapy. NVAF and recent stroke is high-risk population for stroke recurrence even with anticoagulant therapy, and developing optimal secondary prevention strategy is an urgent task.

Catheter ablation (CA) is now widely used to treat symptoms related to NVAF. Some retrospective studies showed a beneficial effect of CA for stroke prevention using age-/sex-matching or propensity-score matching. Moreover, CA have a potential to improve survival or prevent heart failure development in patients with AF. However, the effect of CA for secondary stroke prevention or impact of CA for NVAF patients with recent ischemic stroke for survival or developing heart failure has not been evaluated in a prospective randomized trial. Therefore, in the present study, we intend to compare two groups of patients with NVAF with a history of cerebral infarction: a group receiving standard medical therapy (control group) and a group receiving standard medical therapy plus CA (CA group).

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shoji Furukawa; Phone Number: +81-3-5804-5045; Email: prj-stabled@eps.co.jp

Study Locations

• Japan
  • Aichi, Japan
    • Ichinomiyanishi Hospital
  • Aomori, Japan
    • Hirosaki University Hospital
  • Aomori, Japan
    • Hirosaki Stroke and Rehabilitation Center
  • Chiba, Japan
    • Kimitsu Chuo Hospital
  • Chiba, Japan
    • New Tokyo Heart Clinic
  • Chiba, Japan
    • New Tokyo Hospital
  • Chiba, Japan
    • Nippon Medical School Chiba Hokusoh Hospital
  • Fukuoka, Japan
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan
    • Kokura Memorial Hospital
  • Gifu, Japan
    • Ogaki Municipal Hospital
  • Hiroshima, Japan
    • Hiroshima University Hospital
  • Hiroshima, Japan
    • Hiroshima City Hiroshima Citizens Hospital
  • Hiroshima, Japan
    • Brain Attack Center Ota Memorial Hospital
  • Hiroshima, Japan
    • Fukuyama Cardiovascular Hospital
  • Hiroshima, Japan
    • Suiseikai Kajikawa Hospital
  • Hokkaido, Japan
    • Teine Keijinkai Hospital
  • Hyōgo, Japan
    • Hyogo Brain and Heart Center
  • Hyōgo, Japan
    • Hyogo College of Medicine College Hospital
  • Hyōgo, Japan
    • Kitaharima medical center
  • Kanagawa, Japan
    • Seisho Hospital
  • Kanagawa, Japan
    • Odawara Cardiovascular Hospital
  • Kanazawa, Japan
    • National Hospital Organization Kanazawa Medical Center
  • Kumamoto, Japan
    • Saiseikai Kumamoto Hospital
  • Kumamoto, Japan
    • Kumamoto Red Cross Hospital
  • Morioka, Japan
    • Iwate Medical University
  • Morioka, Japan
    • Iwate Prefectural Central Hospital
  • Nagasaki, Japan
    • Nagasaki University Hospital
  • Nara, Japan
    • Tenri Hospital
  • Okayama, Japan
    • Okayama Red Cross Hospital
  • Osaka, Japan
    • Osaka General Medical Center
  • Osaka, Japan
    • National Cerebral and Cardiovascular Center
  • Osaka, Japan
    • National Hospital Organization Osaka National Hospital
  • Saga, Japan
    • Saga Medical Center Koseikan
  • Saitama, Japan
    • Saitama Medical University International Medical Center
  • Saitama, Japan
    • Saitama Medical Center
  • Tochigi, Japan
    • Jichi Medical University Hospital
  • Tochigi, Japan
    • Dokkyo Medical University Hospital
  • Tokyo, Japan
    • Kyorin University Hospital
  • Tokyo, Japan
    • Juntendo University Hospital
  • Tokyo, Japan
    • Tokyo Women's Medical University Hospital
  • Tokyo, Japan
    • Nippon Medical School
  • Tokyo, Japan
    • Ntt Medical Center Tokyo
  • Tokyo, Japan
    • Jikei University Hospital
  • Tokyo, Japan
    • Showa University Koto Toyosu Hospital
  • Yamagata, Japan
    • Tsuruoka Kyoritsu Hospital
  • Yamagata, Japan
    • Tsuruoka Municipal Shonai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥20 or ≤85 years at time of giving informed consent
• Nonvalvular atrial fibrillation
• History of stroke in previous 6 months
• Current or planned treatment with edoxaban
• Modified Rankin scale ≤3

Exclusion Criteria:

• Symptomatic paroxysmal AF resistant to anti-arrhythmic drugs
• Presence of left atrial thrombus and left atrial appendage on transthoracic echocardiography, computed tomography or magnetic resonance imaging
• Unable to take anticoagulation therapy for any reason, including tendency to bleed or considered at high risk for bleeding from anticoagulation therapy.
• Presence of severe renal disorder (estimated creatinine clearance <30 mL/min by Cockroft-Gault equation)
• Previous CA or surgical intervention for AF
• History of treatment with a left atrial appendage closure device
• Left atrial diameter ≥55 mm on transthoracic echocardiography
• Ejection fraction ≤35% on transthoracic echocardiography
• Persistent AF for ≥10 years
• Pregnant or possibility of pregnancy
• Unlikely to complete the study, such as due to progressive malignant tumor
• Participating or planning to participate in another clinical trial
• Unwilling to participates
• Judged as incompatible for the study by the investigators

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard medical therapy group; The preferred anticoagulant is edoxaban. Antiarrhythmic drugs are administered as needed for the patient by well-trained cardiologists.
Active Comparator: Catheter ablation group; Catheter ablation (CA) should be performed within 1-6 months from the onset of cerebral infarction. CA is based on pulmonary vein isolation, with atrial ablation as required. For conducting CA by a trained and experienced cardiologist, only institutions in which performed >100 CA annually were participated in the present study in principle.	Procedure: Catheter ablation; CA should be performed within 1-6 months from the onset of cerebral infarction. CA is based on pulmonary vein isolation, with atrial ablation as required.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of recurrence of cerebral infarction, systemic embolism, all-cause death, hospitalization for heart failure.	Composite of recurrence of cerebral infarction, systemic embolism, all-cause death, hospitalization for heart failure.	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of cerebral infarction	Recurrence of cerebral infarction	Up to 6 years
Systemic embolism	Symptomatic systemic embolism to other regions than brain, e.g. peripheral or visceral arteries	Up to 6 years
All-cause death	All-cause death	Up to 6 years
Cardiovascular death	Cardiovascular death	Up to 6 years
Hospitalization for heart failure	Hospitalization for heart failure	Up to 6 years
Any bleeding	Any bleeding	Up to 6 years
Intracranial hemorrhage	Intracranial hemorrhage	Up to 6 years
Composite events	all-cause death, onset of stroke, systemic embolism, hospitalization for heart failure, and serious adverse event caused by CA	Up to 6 years
The rate of and related factors to discontinuation of Edoxaban	The rate of and related factors to discontinuation of Edoxaban	Up to 6 years
Recurrence of cerebral infarction in patients with or without discontinuation of Edoxaban	Recurrence of cerebral infarction in patients with or without discontinuation of Edoxaban	Up to 6 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (safety and tolerability)	Incidence of treatment-emergent adverse events (safety and tolerability)	Within 1 month after CA
Incidence of all adverse events, not restricted to CA maneuver-related adverse events	Incidence of all adverse events, not restricted to CA maneuver-related adverse events	Within 1 month after CA
Drug reaction to edoxaban	Drug reaction to edoxaban	Up to 6 years

Collaborators and Investigators

• Sponsor: Nippon Medical School
• Collaborators: Daiichi Sankyo Co., Ltd.
• Investigators: Principal Investigator: Kazumi Kimura, M.D., Ph.D, Department of Neurology, Nippon Medical School

Publications and helpful links

General Publications

• Sakamoto Y, Nishiyama Y, Iwasaki YK, Daida H, Toyoda K, Kitagawa K, Okumura K, Kusano K, Hagiwara N, Fujimoto S, Miyamoto S, Otsuka T, Iguchi Y, Kanamaru T, Yamamoto T, Kaburagi J, Kimura T, Matsumoto T, Kimura K, Shimizu W; STABLED Study Investigators. Design and rationale of the STroke secondary prevention with catheter ABLation and EDoxaban clinical trial in patients with non-valvular atrial fibrillation: The STABLED study. J Cardiol. 2019 Dec;74(6):539-542. doi: 10.1016/j.jjcc.2019.06.002. Epub 2019 Jul 20.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: November 3, 2018
• First Submitted That Met QC Criteria: December 13, 2018
• First Posted (Actual): December 17, 2018

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 11, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: catheter ablation; anticoagulation treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Stroke; Ischemic Stroke; Atrial Fibrillation
• Other Study ID Numbers: LIX-DS-16018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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