Comparison of LAA-Closure vs Oral Anticoagulation in Patients With NVAF and Status Post Intracranial Bleeding.
- Conditions
- Atrial Fibrillation (AF)Intracranial Bleed
- Interventions
- Device: Percutaneous closure of the LAA (Watchman / Watchman FLX)
- Registration Number
- NCT04298723
- Lead Sponsor
- Jena University Hospital
- Brief Summary
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.
- Detailed Description
Within the current trial, two novel strategies are tested in a randomized fashion in patients with atrial fibrillation and status post intracranial bleeding. Patients with ICH were usually excluded from the large NOAC trials and were also not representatively included in the large Watchman device trials. On the other hand, registries show that there is a significant proportion of patients with status post ICH that were implanted with a LAA closure device in clinical routine, and also there are those patients treated with NOAC due to their high stroke risk, despite the risk of recurrent ICH.
Both therapies, NOAC and LAA closure are effective in preventing stroke in patients with AF at high risk for stroke. Also, for both therapies there is evidence for prevention of bleedings, especially intracranial bleeding events.
Patients within the LAA closure group will have the chance after successful closure of the LAA to quit oral anticoagulation medication and therefore reduce their lifetime risk for bleeding and recurrent bleeding. Patients in the NOAC group are provided with an excellent protection against stroke and a significant reduced bleeding risk compared to Vitamin K antagonist therapy.
The trial will help to develop data and hopefully guidelines for management of patients with AF and status post intracranial bleedings. It may help to give physicians data to therapy patients post ICH adequately and help to reduce mortality rates in those patients.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 530
- Signed written informed consent
- Documented atrial fibrillation (paroxysmal, persistent, long-standing persistent or permanent)
- CHA2DS2VASc-Score ≥2
- Status post intracranial bleeding >6 weeks
- Favorable LAA anatomy
- Subject eligible for a LAA occluder device
- Age ≥18 years
- 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
- Functional Impairment (modified ranking scale ≥4 )
- Severe liver failure (Child-Pugh class C or liver failure with coagulopathy)
- Pregnancy or breastfeeding
- Subject with participation in another interventional clinical trial during this study or within 30 days before entry into this trial.
- Known terminating disease with life expectancy <1 year (including those with end-stage heart failure)
- Subjects, who are committed to an institution due to binding official or court order
- Subjects with planned cardiac or non-cardiac surgery or intervention. (These subjects can be included 30 days after intervention / surgery
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Left Atrial Appendage Occlusion Percutaneous closure of the LAA (Watchman / Watchman FLX) Percutaneous closure of the LAA by use of CE-mark approved LAA occlusion device Watchman / Watchman FLX
- Primary Outcome Measures
Name Time Method Event free survival of the composite of Cardiovascular or unexplained death, Stroke (including ischemic or hemorrhagic stroke), Systemic embolism, Bleeding (BARC type 2-5) up to 3 years after randomization 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)
- Secondary Outcome Measures
Name Time Method Cardiovascular or unexplained death per year; Stroke per year; Systemic embolism per year; Bleeding per Year up to 3 years after randomization 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;
Hemorrhagic stroke up to 3 years after randomization An acute episode of focal or global cerebral or spinal dysfunction caused by intraparenchymal, intraventricular, or subarachnoid hemorrhage
Bleeding (BARC type 2-5) up to 3 years after randomization 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)Ischemic stroke up to 3 years after randomization 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.
Combined endpoint: MACCE up to 3 years after randomization Combined endpoint: MACCE (stroke/systemic embolism/cardiovascular death/myocardial infarction)
Mortality up to 3 years after randomization Mortality (including all-cause death, cardiovascular death, non- cardiovascular
Systemic embolism up to 3 years after randomization 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.
Myocardial infarction up to 3 years after randomization A detailed description of the criteria for myocardial infarction can be found in the study protocol.
Intracranial bleeding up to 3 years after randomization Intracranial bleeding
Hospitalization for bleeding or cardiovascular event up to 3 years after randomization Hospitalization for bleeding or cardiovascular event
Trial Locations
- Locations (42)
Universitätsherzzentrum Freiburg - Bad Krozingen
🇩🇪Freiburg, Baden Württemberg, Germany
Universitätsklinikum Saarland
🇩🇪Homburg/Saar, Germany
Universitätsklinikum Schleswig-Holstein (UKSH) Kiel
🇩🇪Kiel, Germany
Westpfalz-Klinikum Kaiserslautern
🇩🇪Kaiserslautern, Germany
Asklepios Klinik Nord- Heidberg
🇩🇪Hamburg-Nord, Germany
Asklepios Klinik Hamburg Wandsbek
🇩🇪Hamburg, Germany
Universityhospital
🇩🇪Jena, Germany
Klinikum Friedrichshafen GmbH
🇩🇪Friedrichshafen, Baden-Wurttemberg, Germany
Universitätsklinikum der J.W. Goethe-Universität Frankfurt
🇩🇪Frankfurt am main, Hessen, Germany
Städtisches Klinikum Friedrichstadt Dresden
🇩🇪Dresden, Sachsen, Germany
HBK Zwickau
🇩🇪Zwickau, Sachsen, Germany
Katholisches Krankenhaus "St. Johann Nepomuk"
🇩🇪Erfurt, Thüringen, Germany
Rhön Klinikum Bad Neustadt
🇩🇪Bad Neustadt an der Saale, Germany
Charité - Universitätsmedizin Berlin (CBF)
🇩🇪Berlin, Germany
Evangelisches Klinikum Bethel Bielefeld
🇩🇪Bielefeld, Germany
REGIOMED Klinikum Coburg
🇩🇪Coburg, Germany
Klinikum Westfalen GmbH Dortmund
🇩🇪Dortmund, Germany
Heart Center Dresden- Universityhospital
🇩🇪Dresden, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Elisabeth-Krankenhaus Essen - Contilia Herz- und Gefäßzentrum Essen
🇩🇪Essen, Germany
Universityhospital Mannheim
🇩🇪Mannheim, Germany
Katholisches Klinikum Koblenz (•Montabaur)
🇩🇪Montabaur, Germany
Helios Klinikum Pirna
🇩🇪Pirna, Germany
Klinikum Vest GmbH
🇩🇪Recklinghausen, Germany
UKE Hamburg
🇩🇪Hamburg, Germany
Knappschaftskrankenhaus Bottrop Gmbh
🇩🇪Bottrop, Nordrhein Westfahlen, Germany
Klinikum Chemnitz
🇩🇪Chemnitz, Sachsen, Germany
Klinikum St. Georg gGmbH
🇩🇪Leipzig, Sachsen, Germany
SRH Wald-Klinikum Gera GmbH
🇩🇪Gera, Thüringen, Germany
CardioVasculäres Centrum Frankfurt (CVC)
🇩🇪Frankfurt, Germany
Klinikum Ingolstadt GmbH
🇩🇪Ingolstadt, Germany
Heart Center Leipzig
🇩🇪Leipzig, Germany
Universityhospital Leipzig
🇩🇪Leipzig, Germany
Universitätsklinikum Schleswig-Holstein (UKSH) Lübeck
🇩🇪Lübeck, Germany
Universityhospital Magdeburg
🇩🇪Magdeburg, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Germany
Marienhaus Kliniken GmbH Neuwied
🇩🇪Neuwied, Germany
Universitätsklinikum Rostock
🇩🇪Rostock, Germany
Asklepios Klinikum St. Georg
🇩🇪Hamburg, Germany
Cardiologicum Hamburg
🇩🇪Hamburg, Germany
Asklepios Klinik Hamburg Altona
🇩🇪Hamburg, Germany