Comparison of LAA-Closure vs Oral Anticoagulation in Patients With NVAF and Status Post Intracranial Bleeding.
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorJena University Hospital
About this trial
Atrial fibrillation is the most common cardiac arrhythmia. In atrial fibrillation, there is a risk that clots can form in the heart, especially in the left atrium. If these clots come loose, there is a risk of stroke. To prevent strokes, patients with atrial fibrillation and status post ICB can be treated with anticoagulants. This medication therapy prevents blood clots from forming in the heart, but can also cause bleeding. Another therapy option is the occlusion of the left atrium. After closure of the left atrium, only a short anticoagulation therapy is necessary until the occluder has healed. The aim of the study is to compare these two treatment approaches. In this study only already approved drugs and occlusion systems will be used.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Signed written informed consent
Documented atrial fibrillation (paroxysmal, persistent, long-standing persistent or permanent)
CHA2DS2VASc-Score ≥2
Status post intracranial bleeding >6 weeks
Disqualifiers
Comorbidities other than AF requiring chronic (N)OAC therapy, e.g. mechanical heart valve prosthesis, hereditary thrombophilia requiring livelong OAC - recurrent thrombosis
Symptomatic carotid disease (if not treated)
Thrombus in the left atrium or left atrial appendage
Active infection or active endocarditis or other infections resulting in bacteremia
Trial design
Design model
Parallel
Treatments tested in this trial
Percutaneous closure of the LAA (Watchman / Watchman FLX)
DeviceLAA closure procedure will be done by experienced operators according to the local SOP. LAA closure will be performed under fluoroscopic and TEE guidance within conscious sedation or general anesthesia. Antibiotic single-shot prophylaxis should be administered peri-procedurally (i.e., cefazolin 2 g). The specific anatomy of the LAA is evaluated and an appropriately sized CE-marked device (Watchman or Watchman FLX) is deployed. LAA angiography and TEE imaging is performed to identify optimal positioning of the device and to exclude a relevant leak. Following device deployment, patients will receive a therapy according to the manufacturers IFU, currently Aspirin and clopidogrel for 3 months followed by single Aspirin up to 12 months. Alternatively, 3 months of NOAC followed by Aspirin monotherapy up to 12 months are possible.
Treatment groups
530 Participants
are divided into 2 treatment groupsGroup A: Left Atrial Appendage OcclusionExperimental treatment 1 intervention
Group B: Best Medical Therapy for AnticoagulationNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)
Cardiovascular or unexplained death Cardiovascular mortality: * Death due to proximate cardiac cause e.g. myocardial infarction, cardiac tamponade, worsening heart failure, or endocarditis * Death caused by non-coronary, non-CNS vascular conditions such as: pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm or other vascular disease * Death from vascular CNS causes from hemorrhagic and ischemic stroke * All procedure-related deaths including those related to a complication of the procedure or treatment for a complication of the procedure * Sudden or unwitnessed death defined as non-traumatic, unexpected fatal event occurring within one hour of the onset of symptoms in an apparently healthy subject. If death is not witness, the definition applies when the victim was in good health 24 hours before the event * Death of unknown cause
Time frame
up to 3 years after randomization2
Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)
Stroke (including ischemic or hemorrhagic stroke) - A stroke is an acute episode (lasting \>24 hours) of focal neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction. Strokes are characterized as follows: * Ischemic stroke: an acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of the central nervous system tissue. Hemorrhage may be a consequence of ischemic stroke. In this situation, the stroke is an ischemic stroke with hemorrhagic transformation and not a hemorrhagic stroke. * Hemorrhagic stroke: an acute episode of focal or global cerebral or spinal dysfunction caused by intraparenchymal, intraventricular, or subarachnoid hemorrhage
Time frame
up to 3 years after randomization3
Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)
Systemic embolism - Non-CNS systemic embolism is defined as abrupt vascular insufficiency of an extremity or organ associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms, (e.g., trauma, atherosclerosis, instrumentation). In the presence of atherosclerotic peripheral vascular disease, diagnosis of embolism to the lower extremities should be made with caution and requires angiographic demonstration of abrupt arterial occlusion.
Time frame
up to 3 years after randomization4
Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)
Bleeding (BARC type 2-5) - Type 2 Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional Type 3 1. Overt bleeding plus hemoglobin drop of 3 to \< 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding 2. Overt bleeding plus hemoglobin drop \< 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents 3. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision Type 4 CABG-related bleeding within 48 hours Type 5 1. Probable fatal bleeding 2. Definite fatal bleeding (overt or autopsy or imaging confirmation)
Time frame
up to 3 years after randomizationSecondary outcomes
1
Cardiovascular or unexplained death per year; Stroke per year; Systemic embolism per year; Bleeding per Year
Primary endpoint events per year: Cardiovascular or unexplained death per year; Stroke per year; Systemic embolism per year; Bleeding per Year; The study participants or, if consent has been obtained, relatives are questioned during the visits, if necessary, diagnostic results are obtained;
Time frame
up to 3 years after randomization2
Combined endpoint: MACCE
Combined endpoint: MACCE (stroke/systemic embolism/cardiovascular death/myocardial infarction)
Time frame
up to 3 years after randomization3
Mortality
Mortality (including all-cause death, cardiovascular death, non- cardiovascular
Time frame
up to 3 years after randomization4
Bleeding (BARC type 2-5)
Type 2 Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional Type 3 1. Overt bleeding plus hemoglobin drop of 3 to \< 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding 2. Overt bleeding plus hemoglobin drop \< 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents 3. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision Type 4 CABG-related bleeding within 48 hours Type 5 1. Probable fatal bleeding 2. Definite fatal bleeding (overt or autopsy or imaging confirmation)
Time frame
up to 3 years after randomizationOther outcomes
1
Secondary Safety Endpoints
* Periprocedural complications within 7 days combined from: pericardial effusion, stroke, major bleeding, device embolization, intracranial bleeding, air embolism * Device related thrombus/fracture/erosion * Vascular access related complications requiring intervention * Procedure-related death * Technical and procedural success of device implantation (LAA closure) * Post-procedure infection rate * Periprocedural outcomes at 7 and 45 calendar days after implantation * Bleeding requiring transfusion (BARC 2-5) * Air embolism
Time frame
As indicated within description.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Jena University Hospital
Lead sponsor
KCRI
Collaborator
Source ClinicalTrials.gov