Atrial Fibrillation, Stroke, Intracerebral Hemorrhage
Conditions
Keywords
Stroke, intracerebral hemorrhage, left atrial appendage occlusion, atrial fibrillation, oral anticoagulation, preventive therapy
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.
Interventions
DEVICELAAO
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.
DRUGMedical 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.
Sponsors
Abbott Medical Devices
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite endpoint of stroke (ischemic or hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality | up to 5 years after randomization | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with a device success | up to 45 days after randomization | Device deployed and implanted in correct position. |
| Number of Participants with a Technical success | up to 45 days after randomization | Exclusion of the left atrial appendage (LAA) achieved without device-related complications and no leak \>5 mm on color Doppler TEE. |
| Number of Participants with a Procedural success | up to 45 days after randomization | 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). |
| Number of Participants with Significant peridevice leak | up to 45 days after randomization | 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. |
| Number of participants with a device-related complication | up to 45 days after randomization | 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 |
| Compare the cognitive status prior to and post treatment | 24 months after randomization | The cognitive status will be assessed by using Montreal Cognitive Assessment (MOCA) and Mini-mental state examination (MMSE) |
| Compare the neurological status prior to and post treatment | 24 months after randomization | The National Institutes of Health Stroke Scale (NIHSS) is used to assess the neurological status |
| Compare the quality of life prior to and post treatment by using EuroQol | 24 months after randomization | 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. |
| Late safety outcome parameters of LAAO and Medical therapy | up to 10 years after randomization | Stroke (ischemic or hemorrhagic), systemic embolism, bleeding, all-cause mortality, intracranial hemorrhage, cardiovascular mortality and unplanned hospitalization will be evaluated |
| Compare the functional status prior to and post treatment | 24 months after randomization | The Modified Rankin Scale (mRS) will be used for measuring the Functional status. |
Countries
Denmark, Finland, Norway, Sweden
Outcome results
None listed