Prevention of Stroke by Left Atrial Appendage Closure in Atrial Fibrillation Patients After Intracerebral Hemorrhage: A Multicenter Randomized Clinical Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Karolinska Institutet
- Enrollment
- 750
- Locations
- 17
- Primary Endpoint
- Composite endpoint of stroke (ischemic or hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •A diagnosis of paroxysmal, persistent or long-standing NVAF with CHA2DS2VASc score >
- •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
Arms & Interventions
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.
Intervention: LAAO (Device)
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.
Intervention: Medical Therapy (Drug)
Outcomes
Primary Outcomes
Composite endpoint of stroke (ischemic or hemorrhagic), systemic embolism, life-threatening or major bleeding and all-cause mortality
Time Frame: 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 Outcomes
- Number of participants with a device-related complication(up to 45 days after randomization)
- Number of Participants with a device success(up to 45 days after randomization)
- Number of Participants with a Technical success(up to 45 days after randomization)
- Number of Participants with a Procedural success(up to 45 days after randomization)
- Number of Participants with Significant peridevice leak(up to 45 days after randomization)
- Compare the functional status prior to and post treatment(24 months after randomization)
- Compare the cognitive status prior to and post treatment(24 months after randomization)
- Compare the neurological status prior to and post treatment(24 months after randomization)
- Compare the quality of life prior to and post treatment by using EuroQol(24 months after randomization)
- Late safety outcome parameters of LAAO and Medical therapy(up to 10 years after randomization)
Investigators
Per Wester
Principal investigator
Karolinska Institutet