Clinical trial NCT02830152: Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage
Official title: Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage: A Multicenter Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Stroke
Intracerebral Hemorrhage
Keywords: Stroke
intracerebral hemorrhage
left atrial appendage occlusion
atrial fibrillation
oral anticoagulation
preventive therapy
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Abbott Medical Devices
First posted: 2016-07-12
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite endpoint of stroke (ischemic or hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality
timeFrame: up to 5 years after randomization
Secondary outcomes:
measure: Number of participants with a device-related complication
timeFrame: up to 45 days after randomization
measure: Number of Participants with a device success
timeFrame: up to 45 days after randomization
measure: Number of Participants with a Technical success
timeFrame: up to 45 days after randomization
measure: Number of Participants with a Procedural success
timeFrame: up to 45 days after randomization
measure: Number of Participants with Significant peridevice leak
timeFrame: up to 45 days after randomization
measure: Compare the functional status prior to and post treatment
timeFrame: 24 months after randomization
measure: Compare the cognitive status prior to and post treatment
timeFrame: 24 months after randomization
measure: Compare the neurological status prior to and post treatment
timeFrame: 24 months after randomization
measure: Compare the quality of life prior to and post treatment by using EuroQol
timeFrame: 24 months after randomization
measure: Late safety outcome parameters of LAAO and Medical therapy
timeFrame: up to 10 years after randomization
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Bispebjerg
country: Denmark
facility: Bispebjerg University Hospital
city: Glostrup
country: Denmark
facility: Rikshospitalet Glostrup
city: Herlev
country: Denmark
facility: Herlev sjukhus
city: Odense
country: Denmark
facility: Odenses Universitetssjukhus
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Joensuu
country: Finland
facility: North Karelia Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Vaasa
country: Finland
facility: Vaasa Centralsjukhus
city: Bergen
country: Norway
facility: Haukeland Universitetssjukhus
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Universitetssjukhuset Skåne
city: Stockholm
country: Sweden
facility: Danderyd Hospital
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
city: Örebro
country: Sweden
facility: Universitetssjukhuset
Study officials:
affiliation: Department of Clinical Sciences, Karolinska Institute, Danderyds hospital
name: Per Wester, MD
role: PRINCIPAL_INVESTIGATOR
References: