NCT04298723: CLEARANCE

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.

Recruiting now NA Last updated 25 August 2025

What this trial tests

NA trial testing Percutaneous closure of the LAA (Watchman / Watchman FLX) in Intracranial Hemorrhages in 530 participants. Currently enrolling.

Timeline

16 June 2020

Primary endpoint
1 June 2029

1 December 2029

Quick facts

Lead sponsor	Jena University Hospital
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	prevention
Enrollment	530
Start date	16 June 2020
Primary completion	1 June 2029
Estimated completion	1 December 2029
Sites	33 locations across Germany, Poland

Drugs / interventions tested

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

Conditions studied

• Intracranial Hemorrhages — all drugs for Intracranial Hemorrhages →
• Atrial Fibrillation (AF) — all drugs for Atrial Fibrillation (AF) →
• Atrial Flutter — all drugs for Atrial Flutter →

Sponsor

Jena University Hospital

Who can join

18 and older, any sex, with Intracranial Hemorrhages or Atrial Fibrillation (AF). Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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 hemorrhagi
• 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 nervo
• 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
• 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 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 hemogl

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation.
   Steffel J, Collins R, Antz M, Cornu P, et al · · 2021 · cited 670× · PMID 33895845 · DOI 10.1093/europace/euab065
2. European Stroke Organisation (ESO) and European Association of Neurosurgical Societies (EANS) guideline on stroke due to spontaneous intracerebral haemorrhage.
   Steiner T, Purrucker JC, Aguiar de Sousa D, Apostolaki-Hansson T, et al · · 2025 · cited 41× · PMID 40401775 · DOI 10.1177/23969873251340815
3. Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives.
   Landmesser U, Skurk C, Tzikas A, Falk V, et al · · 2024 · cited 37× · PMID 39027946 · DOI 10.1093/eurheartj/ehae398
4. Percutaneous Left Atrial Appendage Occlusion-Current Evidence and Future Directions.
   Rotta Detto Loria J, Desch S, Pöss J, Kirsch K, et al · · 2023 · cited 6× · PMID 38068344 · DOI 10.3390/jcm12237292
5. Meta-Analysis of Oral Anticoagulants and Adverse Outcomes in Atrial Fibrillation Patients After Intracranial Hemorrhage.
   Liu X, Guo S, Xu Z. · · 2022 · cited 6× · PMID 35911529 · DOI 10.3389/fcvm.2022.961000
6. Watchman vs. Amulet for Left Atrial Appendage Closure: Current Evidence and Future Perspectives.
   Frazzetto M, Sanfilippo C, Costa G, Contrafatto C, et al · · 2024 · cited 5× · PMID 39200792 · DOI 10.3390/jcm13164651
7. Percutaneous Left Atrial Appendage Occlusion Therapy: Evolution and Growing Evidence.
   Han X, Benditt DG. · · 2023 · cited 4× · PMID 39077005 · DOI 10.31083/j.rcm2407211
8. State-of-the-Art of Transcatheter Left Atrial Appendage Occlusion.
   Pastormerlo LE, De Caterina AR, Esposito A, Korsholm K, et al · · 2024 · cited 4× · PMID 38398253 · DOI 10.3390/jcm13040939