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

Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage: A Multicenter Randomized Clinical Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Atrial Fibrillation; Intracerebral Hemorrhage
• Intervention / Treatment: Device: LAAO; Drug: Medical Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 750
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Bispebjerg, Denmark
    • Bispebjerg University Hospital
  • Glostrup, Denmark
    • Rikshospitalet Glostrup
  • Herlev, Denmark
    • Herlev sjukhus
  • Odense, Denmark
    • Odenses Universitetssjukhus
• Finland
  • Helsinki, Finland
    • Helsinki University Hospital
  • Joensuu, Finland
    • North Karelia Central Hospital
  • Kuopio, Finland
    • Kuopio University Hospital
  • Turku, Finland
    • Turku University Hospital
  • Vaasa, Finland
    • Vaasa Centralsjukhus
• Norway
  • Bergen, Norway
    • Haukeland Universitetssjukhus
  • Oslo, Norway
    • Oslo University Hospital
• Sweden
  • Göteborg, Sweden
    • Sahlgrenska University Hospital
  • Lund, Sweden
    • Universitetssjukhuset Skåne
  • Stockholm, Sweden
    • Danderyd Hospital
  • Uppsala, Sweden
    • Akademiska sjukhuset
  • Örebro, Sweden
    • Universitetssjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Left Atrial Appendage Occlusion (LAAO); 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.	Device: LAAO; The left atrial appendage is occluded with the AMPLATZER™ Amulet™ device, which offers a conformable disc and lobe designed for complete occlusion of the left atrial appendage.; Other Names: AMPLATZER™ Amulet™ (St. Jude Medical)
Active Comparator: Medical Therapy; 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.	Drug: Medical Therapy; Available options included in Medical therapy are: anticoagulation with OAC or NOAC, antiplatelet therapy (including monotherapy and dual antiplatelet therapy) and no pharmacological antithrombotic therapy.; Other Names: Antiplatelet Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 5 years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	up to 45 days after randomization
Number of Participants with a device success	Device deployed and implanted in correct position.	up to 45 days after randomization
Number of Participants with a Technical success	Exclusion of the left atrial appendage (LAA) achieved without device-related complications and no leak >5 mm on color Doppler TEE.	up to 45 days after randomization
Number of Participants with a Procedural success	Technical success and no procedure-related complications, except uncomplicated device embolization (i.e. device embolization resolved by percutaneous retrieval during the procedure without surgical intervention or damage to surrounding cardiovascular structures).	up to 45 days after randomization
Number of Participants with Significant peridevice leak	Consistent with the definition of technical success, a significant peridevice leak is defined as a leak shown as a jet >5 mm on color Doppler TEE.	up to 45 days after randomization
Compare the functional status prior to and post treatment	The Modified Rankin Scale (mRS) will be used for measuring the Functional status.	24 months after randomization
Compare the cognitive status prior to and post treatment	The cognitive status will be assessed by using Montreal Cognitive Assessment (MOCA) and Mini-mental state examination (MMSE)	24 months after randomization
Compare the neurological status prior to and post treatment	The National Institutes of Health Stroke Scale (NIHSS) is used to assess the neurological status	24 months after randomization
Late safety outcome parameters of LAAO and Medical therapy	Stroke (ischemic or hemorrhagic), systemic embolism, bleeding, all-cause mortality, intracranial hemorrhage, cardiovascular mortality and unplanned hospitalization will be evaluated	up to 10 years after randomization
Compare the quality of life prior to and post treatment by using EuroQol	EuroQol assesses health status in terms of five dimension: mobility (walking about); looking after myself; doing usual activities (e.g., going to school, hobbies, sports, playing, doing things with family and friends); having pain or discomfort; and feeling worried, sad, or unhappy. The levels for the dimensions are: 'none/no problems', 'some (problems)', and 'a lot (of problems)'. Higher score represents more problems.	24 months after randomization

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Abbott Medical Devices
• Investigators: Principal Investigator: Per Wester, MD, Department of Clinical Sciences, Karolinska Institute, Danderyds hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2017
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 29, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (Estimated): July 12, 2016

Study Record Updates

• Last Update Posted (Actual): June 12, 2024
• Last Update Submitted That Met QC Criteria: June 11, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Stroke; atrial fibrillation; intracerebral hemorrhage; oral anticoagulation; left atrial appendage occlusion; preventive therapy
• 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; Intracranial Hemorrhages; Stroke; Atrial Fibrillation; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: STROKECLOSE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The full study protocol, statistical plan and informed consent form will be publicly available when results are published. Data will be available on patient level; data will be pseudonymized. The full dataset will be available upon request.
• IPD Sharing Time Frame: Starting after publication and for 36 months.
• IPD Sharing Access Criteria: A full description of the intended use of the data must be sent to the corresponding author for review and approval. Participant consent for data sharing is conditioned and new ethics approval may be required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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