Skip to main content
OpenTrials
Recruiting

NCT Number: NCT04298723

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Intracranial Hemorrhages Arrhythmias, Cardiac Atrial Fibrillation Atrial Fibrillation (AF) Atrial Flutter Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Heart Diseases Hemorrhage Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital Mannheim, Mannheim, Baden-Wurttemberg, Germany

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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)

    Time frame: up to 3 years after randomization

    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

  2. Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)

    Time frame: up to 3 years after randomization

    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

  3. Event free survival of the composite of cardiovascular or unexplained death, stroke (including ischemic or hemorrhagic stroke), systemic embolism, bleeding (BARC type 2-5)

    Time frame: up to 3 years after randomization

    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.

  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)

    Time frame: 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

    • Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding
    • 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
    • Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision

    Type 4

    CABG-related bleeding within 48 hours

    Type 5

    • Probable fatal bleeding
    • Definite fatal bleeding (overt or autopsy or imaging confirmation)

Secondary outcomes

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

    Time frame: 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;

  2. Combined endpoint: MACCE

    Time frame: up to 3 years after randomization

    Combined endpoint: MACCE (stroke/systemic embolism/cardiovascular death/myocardial infarction)

  3. Mortality

    Time frame: up to 3 years after randomization

    Mortality (including all-cause death, cardiovascular death, non- cardiovascular

  4. Bleeding (BARC type 2-5)

    Time frame: 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

    • Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding
    • 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
    • Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision

    Type 4

    CABG-related bleeding within 48 hours

    Type 5

    • Probable fatal bleeding
    • Definite fatal bleeding (overt or autopsy or imaging confirmation)

  5. Systemic embolism

    Time frame: 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.

  6. Ischemic stroke

    Time frame: 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.

  7. Hemorrhagic stroke

    Time frame: up to 3 years after randomization

    An acute episode of focal or global cerebral or spinal dysfunction caused by intraparenchymal, intraventricular, or subarachnoid hemorrhage

  8. Myocardial infarction

    Time frame: up to 3 years after randomization

    A detailed description of the criteria for myocardial infarction can be found in the study protocol.

  9. Hospitalization for bleeding or cardiovascular event

    Time frame: up to 3 years after randomization

    Hospitalization for bleeding or cardiovascular event

  10. Intracranial bleeding

    Time frame: up to 3 years after randomization

    Intracranial bleeding

Other outcomes

  1. Secondary Safety Endpoints

    Time frame: As indicated within description.

    • 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

Study contacts

Contact information is provided by the study sponsor or research team.

Marcus Winter

CONTACT

[email protected]

+4936419396648

Sven Möbius-Winkler, Prof. Dr.

CONTACT

[email protected]

+4936419324503

Sponsors and collaborators

Lead sponsor

Jena University Hospital

Other

Collaborators

  • KCRI

Registry information

Official study 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.

Acronym: CLEARANCE

Important dates

Study start
2020
Primary completion
2029
Study completion
2029
First posted
Mar 6, 2020
Registry last updated
Sep 2, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.