Left Atrial Appendage Occlusion Versus Novel Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation
- Conditions
- StrokeAtrial Fibrillation
- Interventions
- Device: Left atrial appendage occlusionDrug: NOAC
- Registration Number
- NCT03642509
- Lead Sponsor
- University of Aarhus
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 750
- Age ≥ 18 years
- documented non-valvular atrial fibrillation (paroxysmal, persistent or permanent)
- Eligible for long-term Novel Oral Anticoagulation (NOAC) therapy
- Ischemic stroke within the recent 6 months verified by neuroimaging, or
- Transient ischemic attack within 6 months with proven cerebral ischemia based on cerebral magnetic resonance imaging (MRI)
- Modified rankin scale > 3 at time of enrollment
- Glomerular filtration rate (GFR) below 15 ml/min/1.73 m2
- Contraindication towards long-term aspirin therapy
- Planned combined cardiovascular interventional procedures at the time of enrollment
- Terminal illness or cancer with life expectancy less than 2 years.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LAAO group Left atrial appendage occlusion Patients will be treated with transcatheter left atrial appendage occlusion. The LAAO may be performed with the Amulet or Watchman device. NOAC group NOAC Patients will be treated with one of the currently available NOAC drugs; Apixaban, Dabigatran, Edoxaban or Rivaroxaban.
- Primary Outcome Measures
Name Time Method Composite endpoint of stroke (ischemic and hemorrhagic), systemic embolism, major bleeding and all-cause mortality. Up to 5-years from randomization The primary endpoint is the combined rate of stroke, systemic embolism, major bleeding and all-cause mortality.
- Secondary Outcome Measures
Name Time Method Incidence of systemic embolism 2-, 3-, 5- and 10-years 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).
Number of patients with technical success 2 Months Exclusion of the left atrial appendage (LAA) achieved without device-related complications and no leak \>5 mm on color Doppler TEE.
Number of patients with a procedure-related complication 2 months All complications related to the LAAO-procedure will be assessed.
Number of patients with peri-device leaks at follow-up imaging 2 months Detection of any peri-device flow/gap at follow-up cardiac CT/TEE.
Compliance to NOAC 2-, 3-, 5-, and 10-years Adherence to assigned NOAC therapy will be assessed through the National Prescription Registries.
Incidence of major or life-threatening bleeding 2-, 3-, 5- and 10-years 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.
Number of patients with a device success 2 months Device deployed and implanted in correct position
Number of patients with procedural success 2 months 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).
Changes in neurological status based on National Institute of Health (NIH) Stroke scale score 12 months 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 strokeIncidence of ischemic stroke 2-, 3-, 5- and 10-years 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.
Incidence of hemorrhagic stroke 2-, 3-, 5- and 10-years 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.
Incidence of all-cause mortality 2-, 3-, 5- and 10-years The occurrence of death from any cause
Incidence of Transient ischemic attack (TIA) 2-, 3-, 5- and 10-years 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.
Number of patients with a device-related complication 2 months 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 allergyChanges in Quality of life 12 months 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.
Changes in functional status based on Modified Rankin Scale 24 months 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).
Trial Locations
- Locations (15)
Oulu University Hospital
🇫🇮Oulu, Finland
Turku University Hospital
🇫🇮Turku, Finland
Jena University Hospital
🇩🇪Jena, Germany
Oslo University Hospital
🇳🇴Oslo, Norway
Trondheim University Hospital
🇳🇴Trondheim, Norway
Sahlgrenska University Hospital
🇸🇪Göteborg, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Sweden
Skånes University Hospital
🇸🇪Lund, Sweden
Aalborg University Hospital
🇩🇰Aalborg, The North Denmark Region, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Regional Hospital West Jutland
🇩🇰Holstebro, Denmark
Haukeland University Hospital
🇳🇴Bergen, Norway
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Odense University Hospital
🇩🇰Odense, Region Of Southern Denmark, Denmark
Aarhus University Hospital
🇩🇰Aarhus, Central Denmark Region, Denmark