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

Not Applicable

Recruiting

• Conditions: Atrial Fibrillation (AF); Intracranial Bleed

• 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.

Study Timeline

• Study First Submitted: 2020-03-01
• Study First Submitted QC: 2020-03-05
• Study First Posted: 2020-03-06
• Study Start: 2020-06-16
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-15
• Last Update Posted: 2023-03-17
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 530

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

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)
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
Mortality	up to 3 years after randomization	Mortality (including all-cause death, cardiovascular death, non- cardiovascular

Trial Locations

Locations (42)

Universitätsherzzentrum Freiburg - Bad Krozingen; 🇩🇪 Freiburg, Baden Württemberg, Germany

Klinikum Friedrichshafen GmbH; 🇩🇪 Friedrichshafen, Baden-Wurttemberg, Germany

Universitätsklinikum der J.W. Goethe-Universität Frankfurt; 🇩🇪 Frankfurt am main, Hessen, Germany

Knappschaftskrankenhaus Bottrop Gmbh; 🇩🇪 Bottrop, Nordrhein Westfahlen, Germany

Klinikum Chemnitz; 🇩🇪 Chemnitz, Sachsen, Germany

Städtisches Klinikum Friedrichstadt Dresden; 🇩🇪 Dresden, Sachsen, Germany

Klinikum St. Georg gGmbH; 🇩🇪 Leipzig, Sachsen, Germany

HBK Zwickau; 🇩🇪 Zwickau, Sachsen, Germany

Katholisches Krankenhaus "St. Johann Nepomuk"; 🇩🇪 Erfurt, Thüringen, Germany

SRH Wald-Klinikum Gera GmbH; 🇩🇪 Gera, Thüringen, Germany

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