An interventional study of Left atrial appendage occlusion and NOAC in Atrial Fibrillation and Stroke, sponsored by University of Aarhus. Recruiting at 15 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-12-21.
Sponsored by University of Aarhus · Not applicable, Interventional, and Prevention
Atrial fibrillation (AF) is progressively common, and increases the risk of stroke five-fold. Oral anticoagulation is the mainstay therapy; however, it increases the risk of bleeding. Moreover, 30% with AF and at risk of stroke are not in relevant anticoagulation. The randomized PROTECT-AF trial has demonstrated the superiority of left atrial appendage occlusion (LAAO) as compared to warfarin for prevention of the combined endpoint of stroke, major bleeding and cardiovascular mortality. However, studies comparing LAAO to therapy with novel oral anticoagulants (NOAC) have not been carried out.
This study aims to assess the effect of left atrial appendage occlusion (LAAO) to reduce the incidence of stroke, systemic embolism, major bleeding and all-cause mortality in patients with atrial fibrillation (AF) and a prior ischemic stroke or transient ischemic attack (TIA).
An investigator-initiated multicenter, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). The active comparison LAAO is tested against NOAC therapy in a 1:1 stratified randomization. Patients should have AF, and an ischemic stroke or TIA within 6 months prior to enrollment. In total 750 patients will be included. Follow-up will be based on in-office and telephone follow-up during the first 3 years after randomization, along with up to 10 years long-term follow-up through the National Patient Registries.
The main study outcomes: The primary outcome is a composite of stroke (hemorrhagic or ischemic), systemic embolism, major bleeding or all-cause mortality assessed after at least two years follow-up for the last enrolled patient. Secondary outcomes will examine early and late safety outcome measures. The long-term outcome will be assessed up to 10-years after randomization through the National Patient Registries.
3,957 studies on the registry are indexed under Atrial Fibrillation; 933 are open to participants now.
This study's planned enrollment of 750 is above the median of 145 across 2,437 interventional studies indexed under Atrial Fibrillation.
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Exclusion Criteria:
Patients will be treated with transcatheter left atrial appendage occlusion. The LAAO may be performed with the Amulet or Watchman device.
Device: Left atrial appendage occlusion
Patients will be treated with one of the currently available NOAC drugs; Apixaban, Dabigatran, Edoxaban or Rivaroxaban.
Drug: NOAC
Interventional left atrial appendage occlusion with the Amulet or Watchman device
Also known as: Left atrial appendage closure
Medical treatment arm. Patients will be treated with one of the available NOAC drugs; Apixaban, Dabigatran, Edoxaban or Rivaroxaban. The specific drug and dose is at the discretion of the treating physician.
Also known as: Edoxaban, Apixaban, Rivaroxaban, Dabigatran
Composite endpoint of stroke (ischemic and hemorrhagic), systemic embolism, major bleeding and all-cause mortality.
The primary endpoint is the combined rate of stroke, systemic embolism, major bleeding and all-cause mortality.
Time frame: Up to 5-years from randomization
Incidence of ischemic stroke
The occurrence of an acute onset of a focal neurological deficit of presumed vascular origin lasting for ≥ 24 hours or resulting in death. Stroke is categorized as ischemic based on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain or autopsy.
Time frame: 2-, 3-, 5- and 10-years
Incidence of hemorrhagic stroke
The occurrence of an acute onset of a focal neurological deficit of presumed vascular origin lasting for ≥ 24 hours or resulting in death. Stroke is categorized as hemorrhagic based on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain or autopsy.
Time frame: 2-, 3-, 5- and 10-years
Incidence of systemic embolism
The occurrence of an acute vascular insufficiency or occlusion of the extremities or any non-CNS organ associated with clinical, imaging, surgical or autopsy evidence of arterial occlusion in the absence of other likely mechanism (e.g. trauma, atherosclerosis, or instrumentation).
Time frame: 2-, 3-, 5- and 10-years
Incidence of major or life-threatening bleeding
The occurrence of an overt bleeding associated with one or more of the following: decrease in hemoglobin of at least 3.0 g/dL, transfusion of 2 or more units of blood, causing hospitalization, requiring surgery, causing discontinuation of all antithrombotic therapy or pericardial bleeding with/without tamponade or occurring during the index LAAO procedure or during hospitalization for the index procedure (major bleeding). Life-threatening bleeding is defined as fatal bleeding, causing hypovolaemic shock or severe hypotension requiring vasopressor therapy or intervention, symptomatic bleeding in a critical organ (intracranial, intraspinal, intraocular, intramuscular with compartment syndrome, pericardial bleeding after hospitalization for the index LAAO) or overt bleeding with decrease in hemoglobin ≥ 5 g/dL or requiring transfusion of ≥ 4 units of blood.
Time frame: 2-, 3-, 5- and 10-years
Incidence of all-cause mortality
The occurrence of death from any cause
Time frame: 2-, 3-, 5- and 10-years
Incidence of Transient ischemic attack (TIA)
an episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischemia leading to symptoms lasting less than 24 hours, without acute infarction based on neuroimaging.
Time frame: 2-, 3-, 5- and 10-years
Number of patients 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
Time frame: 2 months
Number of patients with a procedure-related complication
All complications related to the LAAO-procedure will be assessed.
Time frame: 2 months
Number of patients with a device success
Device deployed and implanted in correct position
Time frame: 2 months
Number of patients with technical success
Exclusion of the left atrial appendage (LAA) achieved without device-related complications and no leak \>5 mm on color Doppler TEE.
Time frame: 2 Months
Number of patients with 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).
Time frame: 2 months
Number of patients with peri-device leaks at follow-up imaging
Detection of any peri-device flow/gap at follow-up cardiac CT/TEE.
Time frame: 2 months
Changes in functional status based on Modified Rankin Scale
The Modified Rankin scale is used to measure the degree of disability or dependence in daily activities caused by a stroke. The scale runs from 0-6, from no symptoms (0) to death (6).
Time frame: 24 months
Changes in Quality of life
Based on patient self-reported EuroQol-5D questionnaires. The EuroQol-5D is a standardized instrument to measure health-related quality of life. It includes five self-rated dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The questionnaire have 3 levels of severity for each of the five dimensions. It also includes a visual scale from 0 (worst thinkable health condition) to 100 (best thinkable health condition) to report an overall measure.
Time frame: 12 months
Compliance to NOAC
Adherence to assigned NOAC therapy will be assessed through the National Prescription Registries.
Time frame: 2-, 3-, 5-, and 10-years
Changes in neurological status based on National Institute of Health (NIH) Stroke scale score
Assessed by the NIH stroke scale at baseline and 12 month follow-up. A scale to quantify the neurological impairment caused by a stroke. It includes 11 items, each of which scores a specific ability between 0 to 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores are summed to calculate the total NIH Stroke Scale score, that can range from 0 to 42, with 0 being no symptoms. * Score 0: No stroke symptoms * Score 1-4: Minor stroke * Score 5-15: Moderate stroke * Score 16-20: Moderate to severe stroke * Score 21-42: Severe stroke
Time frame: 12 months
Minor bleeding
Any bleeding clinically mentionable that does not qualify as life-threatening, disabling or major.
Time frame: 24 months
Comparison of the cost-effectiveness of LAAO and NOAC therapy
All costs and cost-effectiveness will be evaluated and compared between the two diagnostic strategies.
Time frame: 24 months
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Studies of the drug tested here: Edoxaban