RecruitingPhase 4NCT06212674

Single-stage Pulmonary Vein Isolation Combined With Percutaneous Left Atrial Appendage Occluder Implantation in Patients With Recent Onset Ischemic Stroke and Atrial Fibrillation

Single-stage Pulmonary Vein Isolation Combined With Percutaneous Left Atrial Appendage Occluder Implantation in Patients With Recent Onset Ischemic Stroke and Atrial Fibrillation (PILOS-AF)

Sponsor

Medical University of Silesia

Enrollment

240 participants

Start Date

Oct 31, 2025

Study Type

INTERVENTIONAL

Conditions

Atrial Fibrillation Ischemic Stroke

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria9

Ischemic stroke within 2-12 weeks after randomization with or without reperfusion therapy, confirmed by imaging studies (CT or MRI) that led to mild to moderate psychomotor dysfunction (mRS 0-3; NIHSS <16 points) and was treated with early neurological rehabilitation or was exempt from neurological rehabilitation on account of excellent psychomotor function. An obligatory criterion is persistence of symptoms for >24 h.
Diagnosis of paroxysmal or persistent atrial fibrillation on the basis of 12-lead ECG recording, ECG Holter monitoring, event-recorder or loop recorder at any time, but before the screening visit.
CHA2DS2-VA risk score ≥2 points
Left atrial anatomy (atrial septum, pulmonary vein orifices and left atrial appendage) suitable for intervention (PVI + LAAO or LAAO)
≥ 4 weeks of adequate anticoagulant treatment in the preceding period
no anatomical or functional contraindications and patient consent for transesophageal echocardiography (TEE)
patients with atrial fibrillation who have been adequately treated with anticoagulation (VKA/NOAC) and have had an ischemic stroke
patients without prior history of atrial fibrillation and without anticoagulation who have an ischemic stroke and the atrial fibrillation is clinically overt (de novo)
patients without a prior history of atrial fibrillation, with an initial diagnosis of so-called cryptogenic stroke, in whom further initial ECG monitoring allowed for the detection of clinically silent atrial fibrillation

Exclusion Criteria39

current participation in another clinical trial
lack of informed written consent to participate in the study
age <18 or >80 years
indication for chronic anticoagulant treatment independent of AF:
history of mechanical valve implantation
history of mitral biological valve implantation within 3 months prior to randomization
history of deep vein thrombosis or pulmonary embolism within preceding 6 months or indication for chronic anticoagulation
genetically or immunologically confirmed thrombophilia
contraindications to NOAC treatment:
eGFR ≤15 ml/min/1.73 m2
mechanical valve prosthesis
moderate or severe mitral valve stenosis of rheumatic etiology
life-threatening bleeding during NOAC therapy
Ischemic stroke of etiology other than AF, including cryptogenic stroke without evidence of AF etiology
valvular AF: presence of moderate to severe aortic stenosis of rheumatic etiology
permanent AF
persistent long-standing AF (>1 year)
presence of a thrombus in the left atrial appendage on TEE examination
significant psychomotor dysfunction defined as a modified Rankin Scale (mRS) score of 4-6 or NIHSS score ≥16
major bleeding as defined by ISTH within 14 days prior to randomization or intracranial bleeding ever
active hyperthyroidism
history of myocardial infarction with or without intervention within 90 days prior to randomization
history of PVI or LAAO implantation
history of surgical closure of left atrial appendage
history of percutaneous or surgical ASD/PFO closure
acute or chronic pericarditis
cardiac tamponade
lack of vascular access for PVI and LAAO implantation
chronic heart failure in NYHA functional class IV
left ventricular ejection fraction (LVEF) <30%
chronic kidney disease stage IV-V (eGFR <30 ml/min/1.73 m2)
Child-Pugh class B or C chronic liver failure
severe valvular heart defect
body mass index (BMI, body mass index) ≥40 kg/m2
woman in her childbearing years planning a pregnancy
pregnancy or lactation period
documented life expectancy < 4 years
active cancer < 5 years after remission
active infection, defined as CRP >30 mg/dL with symptoms of respiratory, urinary or gastrointestinal tract infection

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Interventions

PROCEDUREPVI + LAAO, single stage

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.

PROCEDURELAAO

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.

DRUGNOAC

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.