Comparison of LAA-Closure vs Oral Anticoagulation in Patients With NVAF and Status Post Intracranial Bleeding.

NCT04298723 | Recruiting DMC FDA Device

• 1 other identifier: ZKSJ0123_Clearance
• Study Type: interventional
• Target: 530
• Locations: 2 countries
• Sites: 33

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.

Conditions

Intracranial Hemorrhages; Atrial Fibrillation (AF); Atrial Flutter

Keywords

Intracranial Hemorrhage; Intracranial Bleeding; Atrial Fibrillation; Anticoagulation; LAA Occlusion

Outcome Measures

Primary Outcomes (4)

• 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

  up to 3 years after randomization

• 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

  up to 3 years after randomization

• 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.

  up to 3 years after randomization

• 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)

  up to 3 years after randomization

Secondary Outcomes (10)

• Cardiovascular or unexplained death per year; Stroke per year; Systemic embolism per year; Bleeding per Year

  up to 3 years after randomization

• Combined endpoint: MACCE

  up to 3 years after randomization

• Mortality

  up to 3 years after randomization

• Bleeding (BARC type 2-5)

  up to 3 years after randomization

• Systemic embolism

  up to 3 years after randomization

Other Outcomes (1)

• Secondary Safety Endpoints

  As indicated within description.

Study Arms (2)

Left Atrial Appendage Occlusion

EXPERIMENTAL

Percutaneous closure of the LAA by use of CE-mark approved LAA occlusion device Watchman / Watchman FLX

Device: Percutaneous closure of the LAA (Watchman / Watchman FLX)

Best Medical Therapy for Anticoagulation

NO INTERVENTION

Standard of care (according to current guidelines)

Interventions

Percutaneous closure of the LAA (Watchman / Watchman FLX) DEVICE

LAA 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.

Left Atrial Appendage Occlusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jena University Hospital: lead
• KCRI: collaborator

Study Sites (33)

University Hospital Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

RECRUITING

RHÖN-KLINIKUM Campus Bad Neustadt

Bad Neustadt an der Saale, Bavaria, 97616, Germany

ACTIVE NOT RECRUITING

Therapiezentrum Burgau

Burgau, Bavaria, 89331, Germany

ACTIVE NOT RECRUITING

REGIOMED Klinikum Coburg

Coburg, Bavaria, 96450, Germany

RECRUITING

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

RECRUITING

Klinikum Ingolstadt

Ingolstadt, Bavaria, 85049, Germany

RECRUITING

RoMed Klinikum

Rosenheim, Bavaria, 83022, Germany

ACTIVE NOT RECRUITING

Cardiologicum Hamburg

Hamburg, Hamburg, 22041, Germany

RECRUITING

Asklepios Klinik Wandsbek

Hamburg, Hamburg, 22043, Germany

RECRUITING

Asklepios Klinik Nord Heidberg

Hamburg, Hamburg, 22417, Germany

RECRUITING

Asklepios Klinik Altona

Hamburg, Hamburg, 22763, Germany

RECRUITING

Herz-Kreislauf-Zentrum

Rotenburg an der Fulda, Hesse, 44137, Germany

ACTIVE NOT RECRUITING

Evangelisches Klinikum Bethel

Bielefeld, North Rhine-Westphalia, 33617, Germany

RECRUITING

Klinikum Dortmund

Dortmund, North Rhine-Westphalia, 44137, Germany

ACTIVE NOT RECRUITING

Knappschaft Kliniken

Dortmund, North Rhine-Westphalia, 44309, Germany

RECRUITING

Westpfalz-Klinikum

Kaiserslautern, Rhineland-Palatinate, 67655, Germany

RECRUITING

Katholisches Klinikum Koblenz • Montabaur

Koblenz, Rhineland-Palatinate, 56073, Germany

RECRUITING

Klinikum Chemnitz

Chemnitz, Saxony, 09113, Germany

RECRUITING

Dresden Heart Center

Dresden, Saxony, 01307, Germany

RECRUITING

University Hospital Leipzig

Leipzig, Saxony, 04103, Germany

RECRUITING

Klinikum St. Georg

Leipzig, Saxony, 04129, Germany

RECRUITING

Heart Center Leipzig

Leipzig, Saxony, 04289, Germany

RECRUITING

Helios Klinikum Pirna

Pirna, Saxony, 01796, Germany

RECRUITING

Heinrich-Braun-Klinikum (HBK)

Zwickau, Saxony, 08060, Germany

RECRUITING

University Hospital Magdeburg

Magdeburg, Saxony-Anhalt, 68167, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein (UKSH)

Lübeck, Schleswig-Holstein, 23538, Germany

RECRUITING

Charité - Universitätsmedizin Berlin (CBF)

Berlin, State of Berlin, 12203, Germany

RECRUITING

Charité - Universitätsmedizin Berlin (CVK

Berlin, State of Berlin, 13353, Germany

ACTIVE NOT RECRUITING

Helios Klinikum Erfurt

Erfurt, Thuringia, 99089, Germany

RECRUITING

University Hospital Jena

Jena, Thuringia, 07747, Germany

RECRUITING

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, Greater Poland Voivodeship, 61-848, Poland

NOT YET RECRUITING

Polsko-Amerykańskie Kliniki Serca

Bielsko-Biala, Silesian Voivodeship, 43-316, Poland

NOT YET RECRUITING

Górnośląskim Centrum Medycznym

Katowice, Silesian Voivodeship, 40-635, Poland

RECRUITING

MeSH Terms

Conditions

Intracranial Hemorrhages; Atrial Fibrillation; Atrial Flutter

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arrhythmias, Cardiac; Heart Diseases

Study Officials

• Sven Möbius-Winkler, Prof. Dr.

  Department of Internal Medicine I, Jena University Hospital

  PRINCIPAL INVESTIGATOR

• Albrecht Günther, Dr.

  Department of Neurology, Jena University Hospital

  PRINCIPAL INVESTIGATOR

• Christian Senft, Prof. Dr.

  Department of Neurosurgery, Jena University Hospital

  PRINCIPAL INVESTIGATOR

• P. Christian Schulze, Prof. Dr.

  Department of Internal Medicine I, Jena University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sven Möbius-Winkler, Prof. Dr.

CONTACT

+4936419324503; sven.moebius-winkler@med.uni-jena.de

Marcus Winter

CONTACT

+4936419396648; marcus.winter@med.uni-jena.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: CEC blinded DSMB blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Debuty director cardiology departement

Model Details: multicenter, prospective, randomized, controlled, non-blinded clinical trial with a two-arm parallel group design

Study Record Dates

• First Submitted: March 1, 2020
• First Posted: March 6, 2020
• Study Start: June 16, 2020
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 2, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (30); PL (3)