A Phase 4 interventional study of PVI + LAAO, single stage and LAAO in Ischemic Stroke and Atrial Fibrillation, sponsored by Medical University of Silesia. Recruiting at 2 sites in Poland. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-04-13.
Sponsored by Medical University of Silesia · Phase 4, Interventional, and Other
The project is a multicenter, open-label, randomized medical experiment, which was designed to evaluate the efficacy and safety of single-stage pulmonary vein isolation (PVI) and implantation of left atrial appendage occluder (LAAO) in comparison with either isolated LAAO implantation or chronic therapy with non-vitamin K antagonists anticoagulants (NOAC) in patients with recent-onset ischemic stroke and atrial fibrillation (AF). Based on former randomized controlled trials, percutaneous implantation of LAAO was shown to be non-inferior to vitamin K antagonists (VKA), but according to guidelines the use of LAAO is recommended only in patients with absolute contraindication to chronic anticoagulation therapy. PVI constitutes an acknowledged rhythm control management strategy in patients with paroxysmal and persistent AF, which leads to symptomatic relief in about 60% of treated patients, however, its beneficial effect on long-term outcome was demonstrated only in patients with heart failure with reduced ejection fraction. The feasibility and compatibility of both interventions performed as a combined single-stage procedure are warranted by common vascular access via transseptal puncture, which may lead to reduction of procedural cost and shortened overall duration of both interventions. Taking into consideration the preliminary registry data, the combined single-stage PVI and LAAO implantation are thought to be a safe procedure in patients with a high risk of recurrent ischemic stroke and cardiovascular death.
The study will comprise 240 patients who were diagnosed with ischemic stroke within preceding 2-12 weeks, with confirmed paroxysmal or persistent AF and low-to-moderate psychomotor dysfunction in the course of cerebral incident, who completed early neurological rehabilitation and are characterized by high risk of ischemic stroke recurrence (CHA2DS2-VA score ≥2 pts) and who received adequate oral anticoagulation therapy (NOAC/VKA) for ≥4 weeks. After exclusion of thrombus and potential anatomical contraindications to the procedure on transesophageal echocardiography, patients will be randomized in 1:1:1 ratio to study group A treated with combined single-stage PVI + LAAO implantation during 3-day hospitalization or to group B treated with LAAO implantation or control group subject to chronic therapy with NOAC.
Patients in Group A and B will be treated with NOAC until 3 months after procedure. At 3-month visit patients in Group A and B will undergo transesophageal echocardiography so as to confirm procedural success and allow for termination of chronic anticoagulation therapy. If device-related thrombus is excluded and not peri-device leak >=5 mm is present, the patients will be switched from NOAC to aspirin 1x75 mg daily until the end of the trial.
The duration of active enrollment phase will be 12 months. Subsequent follow-up phase will include scheduled outpatient visits (at 3, 12, 48 months) and phone call interview (at 6, 18, 24, 36 months) in order to evaluate the occurrence of clinical and safety endpoints, medical symptoms and signs, quality of life reflected by structured questionnaire, the presence of AF on 24, 7-day or 30-day ECG monitoring (at 12 and 48 months).
Follow-up visits will also include blood laboratory tests analysis, including biomarkers of heart failure and left atrial wall stress, as well as transthoracic echocardiography with tissue Doppler imaging and strain imaging.
Co-primary composite endpoint will comprise cardiovascular death, ischemic stroke, transient ischemic attack, systemic arterial embolism and major non-procedural bleeding, including intracranial bleeding (non-inferiority).
The current project was based on the preliminary results of nonrandomized studies, which delivered evidence for feasibility of combined single-stage PVI and percutaneous left atrial appendage closure and laid ground for future randomized controlled trials. It is expected that the proposed intervention will be non-inferior in terms of composite cerebrovascular events and superior in terms of major nonprocedural bleeding in comparison to chronic NOAC therapy.
Based on the aforementioned inclusion criteria, patients who can be classified into 3. groups will be enrolled in the study:
Exclusion Criteria:
indication for chronic anticoagulant treatment independent of AF:
contraindications to NOAC treatment:
80 patients
Procedure: PVI + LAAO, single stage
80 patients
Procedure: LAAO
80 patients
Drug: NOAC
Treatment with a complex procedure of pulmonary vein isolation (PVI) and left atrial appendage occludder implantation (LAAO) via single transseptal puncture within 4 weeks from randomization. PVI will be performed only by means of radiofrequency (RF) ablation. Other types of PVI will not be allowed (cryoballoon or pulsed field ablation). LAAO implantation will comprise the use of either Amplatzer™ Amulet™ (Abbott) or WATCHMAN FLX™ (Boston Scientific) depending on local center's expertise. The procedure will be carried out within 4 weeks from randomization and will be performed during 3-day hospitalization in cardiology department. The procedure will be preceded by at least 4-week adequate anticoagulation with non-vitamin K antagonists (NOAC). The last dose of NOAC will be administered 12 h (apixaban or dabigatran) or 24 h prior to PVI+LAAO (rivaroxaban). NOAC will be continued for 3 months. Given the exlusion of PDL\>=5 mm or DRT at 3 months, NOAC will be switched to chronic aspirin.
Left atrial appendage occluder implantation (LAAO) will be performed via transseptal puncture under fluoroscopic and TEE guidance. LAAO implantation will comprise the use of either Amplatzer™ Amulet™ (Abbott) or WATCHMAN FLX™ (Boston Scientific) depending on local center's expertise. The procedure will be carried out within 4 weeks from randomization and will be performed during 3-day hospitalization in cardiology department. The procedure will be preceded by at least 4-week adequate anticoagulation with non-vitamin K antagonists (NOAC). The last dose of NOAC will be administered 12 h (apixaban or dabigatran) or 24 h prior to PVI+LAAO (rivaroxaban). NOAC will be continued for 3 months. Given the exlusion of PDL\>=5 mm or DRT at 3 months, NOAC will be switched to chronic aspirin.
Patients will be chronically treated with NOAC including apixaban (2x5 mg or 2x2.5 mg depending on the dose reduction regimen) or dabigatran (2x150 mg or 2x110 mg depending on the dose reduction regimen) or rivaroxaban (1x20 mg or 1x15 mg depending on the dose reduction regimen). The use vitamin K antagonists after the randomization is not allowed.
The rate of cardiovascular deaths, ischemic stroke, transient ischemic attack (TIA), systemic embolism or major bleeding unrelated to the procedure, including intracranial bleeding.
The primary composite endpoint comprises the rate of cardiovascular deaths, ischemic stroke, transient ischemic attack (TIA), systemic embolism or major bleeding unrelated to the procedure, including intracranial bleeding.
Time frame: 12 months
The rate of cardiovascular deaths, ischemic stroke, transient ischemic attack (TIA), systemic embolism or major bleeding unrelated to the procedure, including intracranial bleeding.
The composite primary endpoint comprises the rate of cardiovascular deaths, ischemic stroke, transient ischemic attack (TIA), systemic embolism or major bleeding unrelated to the procedure, including intracranial bleeding.
Time frame: 3, 24 and 48 months
The rate of cardiovascular death
Evaluation of the rate of cardiovascular death
Time frame: 3, 6, 12, 24, 36, 48 months
The rate of ischemic stroke and/or TIA and/or systemic embolism
Evaluation of the rate of ischemic stroke and/or TIA and/or systemic embolism
Time frame: 3, 6, 12, 24, 36, 48 months
The rate of major non-procedural bleeding
Evaluation of the rate of major non-procedural bleeding defined by ISTH
Time frame: 3, 6, 12, 24, 36, 48 months
The rate of all-cause death
Evaluation of the rate of all-cause death
Time frame: 3, 6, 12, 24, 36, 48 months
The proportion of procedural feasibility
Evaluation of the proportion of procedures completed according to prespecified allocation
Time frame: Immediately after intervention
AF burden on Holter ECG monitoring
Proportion of time during 24, 7-day or 30-day monitoring with AF rhythm evaluated by prolonged surface ECG monitoring system.
Time frame: 12 and 48 months
Evaluation of the freedom from AF
Lack of AF episodes on 24-hour, 7-day or 30 day ECG monitoring
Time frame: 12 and 48 months
Change of symptomatic class according to NYHA classification
Evaluation of the change of symptomatic class according to NYHA classification
Time frame: 3, 6, 12, 24, 36 and 48 months
Change of symptomatic class according to EHRA classification
Evaluation of the change of symptomatic class according to EHRA classification
Time frame: 3, 6, 12, 24, 36, 48 months
Evaluation of the change of left ventricular ejection fraction based on transthoracic echocardiography using biplane Simpson's method
Evaluation of the change of left ventricular ejection fraction based on transthoracic echocardiography using biplane Simpson's method
Time frame: 12, 48 months
Evaluation of the change of E/e' based on transthoracic echocardiography
Evaluation of the change of E/e' based on transthoracic echocardiography
Time frame: 12, 48 months
Evaluation of the change of GLS LA strain based on transthoracic echocardiography
Evaluation of the change of GLS LA strain based on transthoracic echocardiography
Time frame: 12, 48 months
Evaluation of the change of segmental LA strain based on transthoracic echocardiography
Evaluation of the change of segmental LA strain based on transthoracic echocardiography
Time frame: 12, 48 months
Change of cardiac biomarker concentration using ELISA method
Change of cardiac biomarker concentration using ELISA method: * NT-proBNP * ST-2 * galectin-3
Time frame: 3 and 12 months
Evaluation of the change of quality of life reflected by EQ-5D questionnaire
Evaluation of the change of quality of life reflected by EQ-5D questionnaire
Time frame: 3, 12 and 48 months
Evaluation of the change of quality of life reflected by KCCQ questionnaire
Evaluation of the change of quality of life reflected by KCCQ questionnaire
Time frame: 3, 12 and 48 months
Evaluation of the change of quality of life reflected by SF-36 questionnaire
Evaluation of the change of quality of life reflected by SF-36 questionnaire
Time frame: 3, 12 and 48 months
Evaluation of the presence of PDL >=5 mm on transesophageal echocardiography at 3 months
Evaluation of the presence of peri-device leak of \>=5 mm on transesophageal echocardiography at 3 months
Time frame: 3 months
Evaluation of the presence of device-related thrombus on transesophageal echocardiography at 3 months
Evaluation of the presence of device-related thrombus on transesophageal echocardiography at 3 months
Time frame: 3 months
Evaluation of short-term procedural safety endpoints
Evaluation of short-term procedural safety endpoints defined as: * pericardial effusion * cardiac tamponade * need for pericardiocentesis * device embolization * procedure-related bleeding * periprocedural ischemic stroke/TIA/systemic embolism * in-hospital death
Time frame: Within 48 hours from the procedure
Evaluation of mid- and long-term procedural safety outcomes
Evaluation of mid-term and long-term safety outcomes: * clinically relevant device-related thrombosis (DRT) * post-procedural pericarditis * pulmonary vein stenosis * atrio-esophageal fistula
Time frame: 3 and 12 months
Plan to share: No — It is forbidden by the Ethics Committee.
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Medical University of Silesia