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

Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02830152
• Other study ID #: STROKECLOSE
• Status: Recruiting
• Phase: N/A
• Start date: May 3, 2017
• Est. completion date: December 2028

Study information

• Verified date: April 2024
• Source: Karolinska Institutet
• Contact: Per Wester
• Phone: +46 70 328 0001
• Email: per.wester[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: December 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage
• Stroke

Intervention

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.

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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska Institutet	Abbott Medical Devices

Countries where clinical trial is conducted

Denmark,  Finland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Number of Participants with a device success	Device deployed and implanted in correct position.	up to 45 days after randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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