Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage

N/AActive Not RecruitingNCT02830152

Karolinska Institutet750 enrolled

Overview

Intracerebral hemorrhage (ICH) in patients with non-valvular atrial fibrillation (NVAF) poses a particular dilemma for thromboprophylaxis. Left atrial appendage occlusion (LAAO) is a non-pharmacological approach to prevent cardiac embolism in NVAF. The risk-benefit ratio of LAAO in patients with NVAF after ICH is unknown. The aim of STROKECLOSE is to assess the effect of LAAO to reduce the incidence stroke, bleeding and cardiovascular mortality in patients with NVAF and prior ICH.

Methods/design: A multicenter prospective randomized open-label clinical trial with blinded outcome evaluation (PROBE design) and blinded safety outcome assessment. The active comparison LAAO is tested against medical therapy in a 2:1 stratified randomization. Study population: Patients should have had an ICH within 12 months prior to enrollment and have NVAF with increased risk of stroke or systemic embolism, as indicated by a CHA2DS2VASc score \>2. In total 750 patients will be included. Active enrollment ensues over 3 years followed by 5 years follow-up and a long-term follow-up at 10 years. Intervention and control: The intervention group will be treated by LAAO, using the Amplatzer Amulet device. Implantation requires a catheterization procedure using venous access and transseptal puncture and is guided by angiography, fluoroscopy and transesophageal echocardiography (TEE) or intracardiac echocardiography (ICE). Recommended post-implant antithrombotic therapy includes aspirin (ASA) therapy for at least 6 months, with or without clopidogrel for the first 45 days after implantation. The control group will receive medical therapy, delivered according to national standards and guidelines at the treating physicians' discretion. This may include oral anticoagulation (OAC) (vitamin-K antagonists, VKA), non-VKA OAC, antiplatelet therapy or no antithrombotic therapy at all. Main study outcomes: The primary outcome is the composite endpoint of stroke (ischemic and hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality, assessed over at least two years. Secondary outcome examines various early and late safety outcome parameters.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * A diagnosis of paroxysmal, persistent or long-standing NVAF with CHA2DS2VASc score \>2. * Clinical and CT/MRI evidence of ICH within 12 months but not less than 4 weeks prior to enrollment. * Age \> 18 years. * Signed informed consent. Exclusion Criteria: * ICH secondary to vascular malformation or tumors * Estimated life expectancy of less than 1 year at eligibility assessment * mRS \> 3 at enrollment * Prior surgical LAA excision * Planned combined interventional procedures at the time of enrollment

Locations (17)

Aarhus University Hospital

Aarhus, Denmark

Bispebjerg University Hospital

Bispebjerg, Denmark

Rikshospitalet Glostrup

Glostrup Municipality, Denmark

Herlev sjukhus

Herlev, Denmark

Odenses Universitetssjukhus

Odense, Denmark

Helsinki University Hospital

Helsinki, Finland

North Karelia Central Hospital

Joensuu, Finland

Kuopio University Hospital

Kuopio, Finland

Turku University Hospital

Turku, Finland

Vaasa Centralsjukhus

Vaasa, Finland

...and 7 more locations

Outcomes

Primary Outcomes

Composite endpoint of stroke (ischemic or hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality

This endpoint will be assessed in patients with paroxysmal, persistent or long-standing NVAF and with ICH within 6 months prior to enrollment. The effect of LAAO will be compared to medical therapy at the treating physician's discretion as a control.

Time frame: up to 5 years after randomization

Secondary Outcomes

Number of participants with a device-related complication

A complication related to the presence of the device. Device-related complications include: * Device embolization * Device erosion * Clinically significant device interference with surrounding structures. This includes structures at the implant location (circumflex coronary artery, mitral valve, pulmonary artery, pulmonary vein) or cardiovascular structures in the vicinity of the location to which the device migrated (if applicable). * Device thrombus * Device fracture * Device infection/endocarditis/pericarditis * Device perforation/laceration * Device allergy