At a glance
- What the study gets you
- Access to the study treatment being tested
- Type of study
- Interventional (receives a drug or procedure)
- Time in hospital
- In-person visits at study sites — visit count not specified by the sponsor
- Drug or intervention
- Left atrial appendage Occlusion (procedure), DOAC (drug)
- How long the study runs
- Study runs about 49 months (dates as stated)
- About the drug or intervention
- Left atrial appendage Occlusion — procedure: Left atrial appendage Occlusion and therapy with direct oral anticoagulants. · DOAC — drug: Therapy with direct oral anticoagulants.
- Patient visit burden
- Not specified by the sponsor
In plain English
This study looks at whether closing off a small pocket in the heart called the left atrial appendage can help people with atrial fibrillation (an irregular heartbeat) who have had an ischaemic stroke (a stroke caused by a blood clot) even while taking blood-thinning medicine (anticoagulants). The study is run by Insel Gruppe AG, University Hospital Bern.
Who can take part
- Age 18 or over
- Agrees to take part in writing (informed consent)
- Has permanent, persistent or paroxysmal (comes and goes) atrial fibrillation, either already known or found during this hospital stay
- Had a stroke caused by a blood clot (ischaemic stroke) with symptoms in the last 3 months
- Was taking blood-thning medicine (anticoagulants) as prescribed when the stroke happened, without stopping for more than 48 hours
- Is taking or will take long-term blood-thinning medicine (a DOAC — a direct oral anticoagulant)
Who may not be able to
- Cannot take DOAC blood-thinning medicine for health reasons
- Expected to live less than 1 year
- Stroke caused by a narrowed artery on the same side, a small deep stroke (lacunar stroke), or other defined causes such as infection of the heart lining, inflamed blood vessels, or a blood clot in the brain's veins
- Has had a hole in the heart (patent foramen ovale) or atrial septum defect closed before
- Rheumatic heart disease
- Severe heart valve disease needing treatment
- Cannot have a transoesophageal echo (a heart scan using a tube passed down the throat), for example due to swollen veins or narrowing in the food pipe, or past food-pipe cancer
- Heart or other surgery within 30 days of joining the study
- Taking part in another study of a heart device or stroke-prevention treatment
- Heart pumping very weakly (left ventricular ejection fraction below 30%)
- Severe kidney problems (the limits depend on which DOAC is used)
- Thickened heart muscle (hypertrophic cardiomyopathy)
- A tumour or blood clot inside the heart
- Sudden worsening of heart failure (acute cardiac decompensation)
- The left atrial appendage is already closed off or tied off
- A blood clot in the left atrial appendage that remains despite 4 weeks of blood thinners (if it disappears with treatment, joining may still be possible)
- Pregnant or breastfeeding
What taking part involves
- • Not stated — ask the trial team
Time commitment: Not stated — ask the trial team about visits, how long the study lasts, and what taking part involves.
Plain-English summary (AI-generated) from registry data. Not eligibility advice — only the trial team can confirm whether you can take part. Use the eligibility checker to see how your health profile matches this trial.
- Type of study
- Testing a treatment
- Ages
- 18 Years and over
- Who
- All
- Number of participants
- 482
- Started
- 2024-05-01
- Last checked
- 2026-04
Plain English Summary
What is this study?
- • Testing a new treatment for ischemic stroke
- • NA - 482 participants
- • Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and cardioembolic stroke due to AF is its major complication
Who can take part?
- • Ages 18 Years and over
- • Diagnosed with ischemic stroke
Where?
- • London - Charing Cross Hospital
- • London - St Bartholomew's Hospital
- • London - St Thomas' Hospital
- • Worthing - University Hospitals Sessex NHS Trust
This is a simplified summary. Always discuss with your doctor before making any decisions.
About This Trial
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 therapy alone. The investigators propose an international, multi-center randomized controlled two-arm trial to assess the effect of LAAO in patients with AF suffering from strokes despite anticoagulation therapy and without competing stroke etiology. The investigators will use the PROBE design with blinded endpoint assessment. The investigators will enrol patients with non-valvular AF and a recent ischemic stroke despite anticoagulation therapy at stroke onset. Patients will be randomized 1:1 to receive LAAO + DOAC therapy (experimental arm) or DOAC therapy alone (standard treatment arm). The primary endpoint is the first occurrence of a composite outcome of recurrent ischemic stroke, systemic embolism and cardiovascular death during follow-up. Secondary outcomes include individual components of the primary composite outcome, safety outcomes (i.e. symptomatic intracranial haemorrhage, major extracranial bleeding, serious device- or procedure-related complication), functional outcome (modified Rankin Scale) and patient-oriented outcomes. The minimum follow-up is 6 months and all patients will receive follow-ups every 6 months until end of study, the maximal follow-up will be 48 months. Based on prior observational data from the investigators' group and others (5 observational studies, \>5000 patients), the investigators estimate the proportion of patients with the primary outcome in the standard treatment arm to be 18% in the first year and 9% in the second year (=cumulative 27% after 2 years). A relative risk reduction of 40% at 2 years would be clinically relevant. Based on these assumptions and a log-rank test, the investigators would need 98 events for a power of 80% at an alpha-level of 5%. Assuming a recruitment rate of 52, 118, 156 and 156 patients in years 1 to 4, an additional 6 months of follow-up (mean follow-up time of 2.1 years) and a uniform drop-out rate of 7.5% per year, 482 patients would need to be enrolled. How to treat patients with an ischemic stroke despite anticoagulation is a major yet unresolved clinical dilemma. This trial has the potential to answer the question whether LAAO plus DOAC therapy is superior to current standard of care for patients with AF who have ischemic stroke despite anticoagulation.
How this trial compares with your answers
Answer 2 more questions to improve match
What we know so far
Still need:
- • Tell us your age for better matching
- • Tell us your sex for better matching
Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.
Eligibility at a Glance
Key info
- Age: 18 Years and over
- Who can join: All genders
What the study is looking for
- ✓Age ≥ 18 years
- ✓Written agreement to take part
- ✓Permanent, persistent, or paroxysmal spontaneous AF previously known or diagnosed during the index hospitalization.
- ✓Recent (≤3 months) causing symptoms ischemic stroke.
- ✓Active or planned long-term therapy with DOAC
Who cannot take part
- ✗Contraindications to DOAC therapy
- ✗Life expectancy \<1 year according to the opinion of the investigator
- ✗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...
See the full criteria
Where Is This Study? (4 UK sites)
Charing Cross Hospital
London, United Kingdom
St Bartholomew's Hospital
London, United Kingdom
St Thomas' Hospital
London, United Kingdom
University Hospitals Sessex NHS Trust
Worthing, United Kingdom
How to Get in Touch
Lorenz Räber, Prof., MD, PhD
Sponsor contactCONTACT
David Seiffge, Prof., MD
Sponsor contactCONTACT