Clinical trial NCT04298723: Comparison of LAA-Closure vs Oral Anticoagulation in Patients With NVAF and Status Post Intracranial Bleeding.
Official title: Randomized Comparison of Interventional Closure of the Left Atrial Appendage Using a LAA Closure Device Versus Oral Anticoagulation Therapy in Patients With Non-valvular Atrial Fibrillation and Status Post Intracranial Bleeding.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation (AF)
Intracranial Bleed
Keywords: Atrial Fibrillation
Intracranial bleeding
LAA occlusion
Anticoagulation
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
First posted: 2020-03-06
Enrollment: 530
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter, prospective, randomized, controlled, non-blinded clinical trial with a two-arm parallel group design
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Event free survival of the composite of Cardiovascular or unexplained death, Stroke (including ischemic or hemorrhagic stroke), Systemic embolism, Bleeding (BARC type 2-5)
timeFrame: up to 3 years after randomization
measure: Event free survival of the composite of Cardiovascular or unexplained death, Stroke (including ischemic or hemorrhagic stroke), Systemic embolism, Bleeding (BARC type 2-5)
timeFrame: up to 3 years after randomization
measure: Event free survival of the composite of Cardiovascular or unexplained death, Stroke (including ischemic or hemorrhagic stroke), Systemic embolism, Bleeding (BARC type 2-5)
timeFrame: up to 3 years after randomization
measure: Event free survival of the composite of Cardiovascular or unexplained death, Stroke (including ischemic or hemorrhagic stroke), Systemic embolism, Bleeding (BARC type 2-5)
timeFrame: up to 3 years after randomization
Secondary outcomes:
measure: Cardiovascular or unexplained death per year; Stroke per year; Systemic embolism per year; Bleeding per Year
timeFrame: up to 3 years after randomization
measure: Combined endpoint: MACCE
timeFrame: up to 3 years after randomization
measure: Mortality
timeFrame: up to 3 years after randomization
measure: Bleeding (BARC type 2-5)
timeFrame: up to 3 years after randomization
measure: Systemic embolism
timeFrame: up to 3 years after randomization
measure: Ischemic stroke
timeFrame: up to 3 years after randomization
measure: Hemorrhagic stroke
timeFrame: up to 3 years after randomization
measure: Myocardial infarction
timeFrame: up to 3 years after randomization
measure: Hospitalization for bleeding or cardiovascular event
timeFrame: up to 3 years after randomization
measure: Intracranial bleeding
timeFrame: up to 3 years after randomization
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Universitätsherzzentrum Freiburg - Bad Krozingen
state: Baden Württemberg
city: Friedrichshafen
country: Germany
facility: Klinikum Friedrichshafen GmbH
state: Baden-Wurttemberg
city: Frankfurt am main
country: Germany
facility: Universitätsklinikum der J.W. Goethe-Universität Frankfurt
state: Hessen
city: Bottrop
country: Germany
facility: Knappschaftskrankenhaus Bottrop Gmbh
state: Nordrhein Westfahlen
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
state: Sachsen
city: Dresden
country: Germany
facility: Städtisches Klinikum Friedrichstadt Dresden
state: Sachsen
city: Leipzig
country: Germany
facility: Klinikum St. Georg gGmbH
state: Sachsen
city: Zwickau
country: Germany
facility: HBK Zwickau
state: Sachsen
city: Erfurt
country: Germany
facility: Katholisches Krankenhaus "St. Johann Nepomuk"
state: Thüringen
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH
state: Thüringen
city: Bad Neustadt an der Saale
country: Germany
facility: Rhön Klinikum Bad Neustadt
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin (CBF)
city: Bielefeld
country: Germany
facility: Evangelisches Klinikum Bethel Bielefeld
city: Coburg
country: Germany
facility: REGIOMED Klinikum Coburg
city: Dortmund
country: Germany
facility: Klinikum Westfalen GmbH Dortmund
city: Dresden
country: Germany
facility: Heart Center Dresden- Universityhospital
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Elisabeth-Krankenhaus Essen - Contilia Herz- und Gefäßzentrum Essen
city: Frankfurt
country: Germany
facility: CardioVasculäres Centrum Frankfurt (CVC)
city: Hamburg-Nord
country: Germany
facility: Asklepios Klinik Nord- Heidberg
city: Hamburg
country: Germany
facility: Asklepios Klinikum St. Georg
city: Hamburg
country: Germany
facility: UKE Hamburg
city: Hamburg
country: Germany
facility: Cardiologicum Hamburg
city: Hamburg
country: Germany
facility: Asklepios Klinik Hamburg Wandsbek
city: Hamburg
country: Germany
facility: Asklepios Klinik Hamburg Altona
city: Homburg/Saar
country: Germany
facility: Universitätsklinikum Saarland
city: Ingolstadt
country: Germany
facility: Klinikum Ingolstadt GmbH
city: Jena
country: Germany
facility: Universityhospital
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum Kaiserslautern
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein (UKSH) Kiel
city: Leipzig
country: Germany
facility: Heart Center Leipzig
city: Leipzig
country: Germany
facility: Universityhospital Leipzig
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein (UKSH) Lübeck
city: Magdeburg
country: Germany
facility: Universityhospital Magdeburg
city: Mannheim
country: Germany
facility: Universityhospital Mannheim
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: Montabaur
country: Germany
facility: Katholisches Klinikum Koblenz (•Montabaur)
city: Neuwied
country: Germany
facility: Marienhaus Kliniken GmbH Neuwied
city: Pirna
country: Germany
facility: Helios Klinikum Pirna
city: Recklinghausen
country: Germany
facility: Klinikum Vest GmbH
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock
Study officials:
affiliation: Department of Internal Medicine I, Jena University Hospital
name: Sven Möbius-Winkler, Univ. Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neurology, Jena University Hospital
name: Albrecht Günther, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neurosurgery, RHÖN-KLINIKUM Campus Bad Neustadt
name: Albrecht Waschke, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine I, Jena University Hospital
name: P. Christian Schulze, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: