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

Karolinska Institute

Status: Active, not recruiting

Conditions: Atrial Fibrillation; Stroke; Intracerebral Hemorrhage

Treatments: Drug: Medical Therapy; Device: LAAO

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02830152

STROKECLOSE

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 750 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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750 participants in 2 patient groups

Left Atrial Appendage Occlusion (LAAO)

Experimental group

Description:

The intervention is implantation of Amplatzer Amulet LAAO device within two months after randomization. Device implantation comprises a catheterization procedure using venous access and a transseptal puncture to obtain access to the left atrium (LA). Procedural imaging guidance is left to the physician's discretion and may include several techniques such as angiography/fluoroscopy, transesophageal echocardiography (TEE) and/or intracardiac echocardiography (ICE). Recommended post-implant antithrombotic therapy includes ASA therapy for at least 6 months, which may be combined with clopidogrel for the first 45 days after implantation.

Treatment:

Device: LAAO

Medical Therapy

Active Comparator group

Description:

The optimal medical therapy of stroke prevention in non-valvular atrial fibrillation (NVAF) after intracerebral hemorrhage (ICH) is not known. Therefore, it will be left to the discretion of the treating physician to decide if, when, and which pharmacological therapy will be prescribed. Available options include anticoagulation with oral anticoagulation (OAC) or novel oral anticoagulants (NOAC), antiplatelet therapy (including monotherapy and dual antiplatelet therapy) and no pharmacological antithrombotic therapy.

Treatment:

Drug: Medical Therapy