Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic StrokE Despite Anticoagulation Therapy

Plain English Summary

Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy is a Not Applicable clinical trial sponsored by Insel Gruppe AG, University Hospital Bern studying Ischemic Stroke, Atrial Fibrillation. This trial tests a procedure to close a small heart pouch called the left atrial appendage (LAA) in addition to blood thinner medication. It is for patients who have atrial fibrillation (AFib) and have recently had an ischemic stroke, even while taking blood thinners. Participants will be randomly assigned to either receive the LAA closure device plus blood thinners, or just blood thinners. Existing treatments for stroke prevention in AFib patients include adjusting blood thinner dosages or adding other medications. The trial aims to enroll 482 participants.

Official Summary

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and cardioembolic stroke due to AF is its major complication. Direct oral anticoagulants (DOAC) reduce the risk of cardioembolism in patients with AF. Despite DOAC therapy, there is a significant residual stroke risk of 1-2%/year. Recent data from the Swiss Stroke Registry found 38% of patients with AF and ischemic stroke were on prior anticoagulant therapy (approximately 400 patients per year in Switzerland). The investigators found in a prior observational study, that patients with AF who have ischemic stroke despite anticoagulation are at increased risk of having another ischemic stroke (HR 1.6; 95% confidence interval, CI 1.1-2.1). Combining observational data from 11 international stroke centres, the investigators found that the majority of ischemic strokes despite anticoagulation in patients with AF is "breakthrough" cardioembolism (76% of patients) and only a minority of 24% is related to other causes unrelated to AF. Optimal secondary prevention strategy is unknown. The investigators have conducted two independent observational studies including together \>4000 patients but did not identify any strategy (e.g. switch to different DOAC, additional antiplatelet therapy) that seems superior. A recent randomized controlled trial on surgical occlusion of the left atrial appendage (LAAO) found that LAAO may provide additional protection from ischaemic stroke in addition to oral anticoagulation. Triggered by this finding, the investigators performed a matched retrospective observational study and found that patients with AF and stroke despite anticoagulation who received a combined mechanical-pharmacological therapy (DOAC therapy + LAAO) had lower rates of adverse outcomes compared to those with DOAC therapy alone. Therefore, the investigators hypothesize that in patients with AF and ischemic stroke despite anticoagulant therapy, LAAO in addition to anticoagulation with a DOAC is superior to DOAC

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older who have been diagnosed with AFib and have had a stroke within the last 3 months. Patients must be currently taking or planning to take a specific type of blood thinner called a Direct Oral Anticoagulant (DOAC). Individuals with certain other heart conditions, severe kidney problems, a life expectancy less than one year, or those who have had recent surgery may not be eligible. This trial is studying Ischemic Stroke, Atrial Fibrillation, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if the combination of a device to close the left atrial appendage and blood thinners reduces the risk of having another stroke, experiencing a systemic embolism, or dying from The specific primary outcome measures are: Composite of recurrent ischemic stroke, systemic embolism, or cardiovascular death (whatever comes first). (6 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial addresses a critical gap in stroke prevention for AFib patients who continue to have strokes despite being on standard blood thinner therapy. This research targets Ischemic Stroke, Atrial Fibrillation, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in stroke prevention for a large AFib patient population, potentially offering a new therapeutic option and impacting the market for cardiovascular devices

Is This Trial Right for Me?

Ask your doctor if you have had a stroke despite taking blood thinners and if this trial might be an option for you. Participation involves a procedure to implant a device and regular follow-up appointments to monitor your health and any potential side effects. You will continue to take your prescribed blood thinner medication throughout the study. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: SINGLE
• Enrollment: 482 participants

Interventions

• PROCEDURE: Left atrial appendage Occlusion — Left atrial appendage Occlusion and therapy with direct oral anticoagulants. Choice of DOAC is at the discretion of the treating physician.
• DRUG: DOAC — Therapy with direct oral anticoagulants. Choice of DOAC is at the discretion of the treating physician.

Primary Outcomes

• Composite of recurrent ischemic stroke, systemic embolism, or cardiovascular death (whatever comes first). (6 months)

Secondary Outcomes

• Recurrent ischemic stroke (6 months)
• Systemic embolism (6 months)
• Cardiovascular death (6 months)
• Symptomatic intracranial hemorrhage (6 months)
• Major extracranial bleeding (ISTH) (6 months)

Full Eligibility Criteria

Inclusion Criteria:

* Age ≥ 18 years
* Written informed consent
* Permanent, persistent, or paroxysmal spontaneous AF previously known or diagnosed during the index hospitalization.
* Recent (≤3 months) symptomatic ischemic stroke.
* Active and ongoing anticoagulation therapy at stroke onset assessed based on medical history (i.e. any therapeutic oral anticoagulation therapy \[Vitamin K antagonist/DOAC according to prescription recommendations for AF; inadequate low-dose DOAC therapy allowed for inclusion\] not stopped/paused for \>48 hours due to any reason, i.e. medical intervention or non-adherence).
* Active or planned long-term therapy with DOAC

Exclusion Criteria:

* Contraindications to DOAC therapy
* Life expectancy \<1 year according to the opinion of the investigator
* Stroke due to: Ipsilateral intra/extracranial high-grade stenosis, Isolated lacunar stroke, Other well-defined stroke aetiologies (i.e., endocarditis, vasculitis, Reversible Cerebral Vasoconstriction Syndrome \[RCVS\], Posterior Reversible Encephalopathy Syndrome \[PRES\], cerebral sinus venous thrombosis)
* Previous persistent foramen ovale or atrial septum defect closure.
* Rheumatic heart disease
* Severe heart valve disease that requires treatment (severe aortic stenosis or regurgitation, severe mitral stenosis or regurgitation).
* Contraindications for TEE (relevant esophageal varices, esophageal stricture, history of esophageal cancer).
* Cardiac or non-cardiac surgical procedure within 30 days of randomization
* Enrolled in another investigation of a cardiovascular device or investigating secondary prevention therapy.
* Severely reduced Left Ventricular Ejection Fraction (LVEF) \<30%.
* Severe renal impairment as described in the summary of medicinal product characteristics for the chosen DOAC (e.g. rivaroxaban, apixaban and edoxaban creatinine clearance \<15 ml/min; dabigatran creatinine clearance \<30 ml/min).
* Hypertrophic cardiomyopathy
* Intracardiac tumor
* Ventricular thrombus
* Acute cardiac decompensation
* LAA is obliterated or surgically ligated
* Persistent proximal LAA thrombus despite 4 weeks of anticoagulation (if a proximal thrombus in the LAA is found, anticoagulation with vitamin K antagonist (INR 2.5-3.5) may be started, and if the thrombus disappears, the patient may be eligible for LAAO)
* Pregnancy or breastfeeding (pregnancy test in urine or blood to be performed at screening for women of childbearing potential)

Trial Locations

• AZ Sint Jan Brugge, Bruges, Belgium
• Brussels University Hospital, Brussels, Belgium
• UCLouvain - Cliniques universitaires Saint-Luc, Brussels, Belgium
• HUmani CHU Charleroi-Chimay, Charleroi, Belgium
• Universitair Ziekenhuis (UZ) Leuven, Leuven, Belgium
• UKSH, Campus Lübeck, Lübeck, Schleswig-Holstein, Germany
• Charité-Universitätsmedizin Berlin, Berlin, Germany
• Universitätsklinikum Bonn, Bonn, Germany
• Universitätsmedizin Göttingen, Göttingen, Germany
• Asklepios Klinik Altona, Hamburg, Germany
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Ischemic Stroke
• Atrial Fibrillation
• Cardioembolic Stroke
• Anticoagulation Therapy
• Blood Thinners
• Left Atrial Appendage Occlusion
• Cardiovascular Disease
• Arrhythmia
• Secondary Stroke Prevention
• Heart Failure

More Ischemic Stroke Trials

View all Ischemic Stroke clinical trials