Clinical trial NCT03777631: STroke Secondary Prevention With Catheter ABLation and EDoxaban for Patients With Non-valvular Atrial Fibrillation: STABLED Study
Official title: STroke Secondary Prevention With Catheter ABLation and EDoxaban for Patients With Non-valvular Atrial Fibrillation: STABLED Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Ischemic Stroke
Atrial Fibrillation Non-Rheumatic
Keywords: anticoagulation treatment
catheter ablation
Lead sponsor: Nippon Medical School
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo Co., Ltd.
First posted: 2018-12-17
Enrollment: 251
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The included patients were randomly allocated to two groups: (1) Standard medical treatment group and (2) Catheter ablation additional group.
Primary purpose: PREVENTION

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Composite of recurrence of cerebral infarction, systemic embolism, all-cause death, hospitalization for heart failure.
timeFrame: Up to 6 years
Secondary outcomes:
measure: Recurrence of cerebral infarction
timeFrame: Up to 6 years
measure: Systemic embolism
timeFrame: Up to 6 years
measure: All-cause death
timeFrame: Up to 6 years
measure: Cardiovascular death
timeFrame: Up to 6 years
measure: Hospitalization for heart failure
timeFrame: Up to 6 years
measure: Any bleeding
timeFrame: Up to 6 years
measure: Intracranial hemorrhage
timeFrame: Up to 6 years
measure: Composite events
timeFrame: Up to 6 years
measure: The rate of and related factors to discontinuation of Edoxaban
timeFrame: Up to 6 years
measure: Recurrence of cerebral infarction in patients with or without discontinuation of Edoxaban
timeFrame: Up to 6 years
Other outcomes:
measure: Incidence of treatment-emergent adverse events (safety and tolerability)
timeFrame: Within 1 month after CA
measure: Incidence of all adverse events, not restricted to CA maneuver-related adverse events
timeFrame: Within 1 month after CA
measure: Drug reaction to edoxaban
timeFrame: Up to 6 years
Locations:
city: Aichi
country: Japan
facility: Ichinomiyanishi Hospital
city: Aomori
country: Japan
facility: Hirosaki Stroke and Rehabilitation Center
city: Aomori
country: Japan
facility: Hirosaki University Hospital
city: Chiba
country: Japan
facility: Kimitsu Chuo Hospital
city: Chiba
country: Japan
facility: New Tokyo Heart Clinic
city: Chiba
country: Japan
facility: New Tokyo Hospital
city: Chiba
country: Japan
facility: Nippon Medical School Chiba Hokusoh Hospital
city: Fukuoka
country: Japan
facility: Kokura Memorial Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Gifu
country: Japan
facility: Ogaki Municipal Hospital
city: Hiroshima
country: Japan
facility: Brain Attack Center Ota Memorial Hospital
city: Hiroshima
country: Japan
facility: Fukuyama Cardiovascular Hospital
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hiroshima
country: Japan
facility: Suiseikai Kajikawa Hospital
city: Hokkaido
country: Japan
facility: Teine Keijinkai Hospital
city: Hyōgo
country: Japan
facility: Hyogo Brain and Heart Center
city: Hyōgo
country: Japan
facility: Hyogo College of Medicine College Hospital
city: Hyōgo
country: Japan
facility: Kitaharima medical center
city: Kanagawa
country: Japan
facility: Odawara Cardiovascular Hospital
city: Kanagawa
country: Japan
facility: Seisho Hospital
city: Kanazawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
city: Kumamoto
country: Japan
facility: Kumamoto Red Cross Hospital
city: Kumamoto
country: Japan
facility: Saiseikai Kumamoto Hospital
city: Morioka
country: Japan
facility: Iwate Medical University
city: Morioka
country: Japan
facility: Iwate Prefectural Central Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Nara
country: Japan
facility: Tenri Hospital
city: Okayama
country: Japan
facility: Okayama Red Cross Hospital
city: Osaka
country: Japan
facility: National Cerebral and Cardiovascular Center
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Saga
country: Japan
facility: Saga Medical Center Koseikan
city: Saitama
country: Japan
facility: Saitama Medical Center
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center
city: Tochigi
country: Japan
facility: Dokkyo Medical University Hospital
city: Tochigi
country: Japan
facility: Jichi Medical University Hospital
city: Tokyo
country: Japan
facility: Jikei University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Kyorin University Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School
city: Tokyo
country: Japan
facility: NTT Medical Center Tokyo
city: Tokyo
country: Japan
facility: Showa University Koto Toyosu Hospital
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Yamagata
country: Japan
facility: Tsuruoka Kyoritsu Hospital
city: Yamagata
country: Japan
facility: Tsuruoka Municipal Shonai Hospital
Study officials:
affiliation: Department of Neurology, Nippon Medical School
name: Kazumi Kimura, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.