Closure of the left atrial appendage after a stroke in patients with atrial fibrillation.
Summary description of the study
Strokes are one of the most common complications in patients with atrial fibrillation (a heart rhythm disorder). Standard therapy with anticoagulant medications significantly reduces the risk of stroke. However, despite medication treatment, strokes continue to occur in patients with atrial fibrillation. Additionally, these patients have a significantly increased risk of recurrent strokes, vascular occlusions, and fatal disease progression. New studies in humans suggest that an interventional closure of the left atrial appendage in the heart may prevent recurrent strokes. Therefore, we are investigating in this study whether interventional closure of the left atrial appendage in stroke patients with atrial fibrillation, in combination with anticoagulant medications, is effective and can reduce the risk of recurrent strokes, vascular occlusions, and fatal disease progression.
(BASEC)
Intervention under investigation
The LAA closure refers to the interventional closure of the left atrial appendage, which serves to prevent cardioembolic strokes in patients with atrial fibrillation. The closure of the left atrial appendage is performed via an occlusion system, which is advanced through a catheter via the right femoral vein to the heart. After puncturing the atrial septum, the occlusion system is placed in the left atrial appendage.
(BASEC)
Disease under investigation
This study investigates the efficacy and safety of closure of the left atrial appendage in stroke patients with atrial fibrillation.
(BASEC)
Inclusion criteria: • Age ≥ 18 years • Written consent according to country-specific details • Existing, persistent, or paroxysmal spontaneous atrial fibrillation (AF), previously known or diagnosed during the index hospitalization. Recently occurred (≤3 months) ischemic stroke • Active and ongoing anticoagulation therapy at the time of the stroke, assessed based on the medical history (i.e., any therapeutic oral anticoagulation therapy [vitamin K antagonist/DOAC according to prescription recommendations for AF; insufficient low-dose DOAC therapy for inclusion criteria is allowed], which has not been stopped/interrupted for any reason for >48 hours, whether due to a medical procedure or due to non-compliance). • Active or planned long-term therapy with DOAC. (BASEC)
Exclusion criteria
Exclusion criteria: • Contraindication for DOAC therapy • Life expectancy <1 year according to the investigator's assessment • Stroke due to: • Ipsilateral high-grade stenosis (intra-/extracranial; without simultaneous ipsilateral high-grade stenosis) • Isolated lacunar stroke • Other clearly defined stroke etiologies (e.g., endocarditis, vasculitis, reversible cerebral vasoconstriction syndrome [RCVS], posterior reversible encephalopathy syndrome [PRES], cerebral venous sinus thrombosis) • Previous persistent foramen ovale or atrial septal defect closure • Rheumatic heart disease • Severe valvular heart disease requiring treatment (severe aortic stenosis or insufficiency, severe mitral stenosis or insufficiency) • Contraindications for TEE (large esophageal varices, esophageal stenosis, history of esophageal cancer) • Cardiac or non-cardiac surgical interventions within 30 days after randomization • Participation in another investigation of a cardiovascular device or the investigation of a secondary prevention treatment • Severe renal impairment according to the summary of product characteristics of the chosen DOAC (e.g., rivaroxaban, apixaban, and edoxaban creatinine clearance <15 ml/min; dabigatran creatinine clearance <30 ml/min) • Significantly reduced left ventricular ejection fraction (LVEF) <30%. • 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 is found in the LAA, anticoagulation with warfarin (INR 2.5-3.5) may be initiated, and if the thrombus disappears, the patient may be eligible for LAAO). • Pregnancy or breastfeeding (pregnancy test in urine or blood to be performed in women of childbearing age during screening). (BASEC)
Trial sites
Basel, Bern, Geneva, Lausanne, Lugano, Luzern, St. Gallen
(BASEC)
Sponsor
Insel Gruppe AG, Inselspital Bern
(BASEC)
Contact
Contact Person Switzerland
Prof. Dr. med. Lorenz Räber, PhD
+41 31 632 09 29
lorenz.raeber@clutterinsel.chUniversitätsklinik für Kardiologie Inselspital Bern Herz Gefäss Zentrum Freiburgstrasse CH-3010 Bern
(BASEC)
General Information
Cardiovascular Center, Inselspital Bern,
+41316320929
lorenz.raeber@clutterinsel.ch(ICTRP)
General Information
Cardiovascular Center, Inselspital Bern
+41316320929
lorenz.raeber@clutterinsel.ch(ICTRP)
Scientific Information
Cardiovascular Center, Inselspital Bern,
+41316320929
lorenz.raeber@clutterinsel.ch(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Bern
(BASEC)
Date of authorisation
01.05.2024
(BASEC)
ICTRP Trial ID
NCT05976685 (ICTRP)
Official title (approved by ethics committee)
Frühzeitiger Verschluss des linken Vorhofohrs bei Patienten mit Vorhof-flimmern und ischämischem Schlaganfall trotz Antikoagulationstherapie. (BASEC)
Academic title
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic StrokE Despite Anticoagulation Therapy (ICTRP)
Public title
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy (ICTRP)
Disease under investigation
Ischemic StrokeAtrial Fibrillation (ICTRP)
Intervention under investigation
Procedure: Left atrial appendage OcclusionDrug: DOAC (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Single (Outcomes Assessor). (ICTRP)
Inclusion/Exclusion 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) (ICTRP)
not available
Primary and secondary end points
Composite of recurrent ischemic stroke, systemic embolism, or cardiovascular death (whatever comes first). (ICTRP)
Recurrent ischemic stroke;Systemic embolism;Cardiovascular death;Symptomatic intracranial hemorrhage;Major extracranial bleeding (ISTH);Procedure-related death;Serious device- or procedure-related complication;All-cause hospitalization;Cause-specific hospitalization;Global health;Global safety;Functional neurological outcome (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Lorenz R?ber, Prof., MD;Lorenz R?ber, Prof., MD, PhD, Lorenz.Raeber@insel.ch, +41316320929, Cardiovascular Center, Inselspital Bern, (ICTRP)
Secondary trial IDs
2023-02340 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT05976685 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available