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

NCT06212674 | Recruiting Phase 4 DMC

• 2 other identifiers: PILOS-AF_v3.02023/ABM/01/00074-00
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Atrial Fibrillation; Ischemic Stroke

Keywords

Pulmonary vein isolation; Occluder implantation; PILOS; PILOS-AF; LAA ocludder implantation; ischemic stroke; atrial fibrillation

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (20)

• The rate of cardiovascular deaths, ischemic stroke, transient ischemic attack (TIA), systemic embolism or major bleeding unrelated to the procedure, including intracranial bleeding.

  3, 24 and 48 months

• The rate of cardiovascular death

  3, 6, 12, 24, 36, 48 months

• The rate of ischemic stroke and/or TIA and/or systemic embolism

  3, 6, 12, 24, 36, 48 months

• The rate of major non-procedural bleeding

  3, 6, 12, 24, 36, 48 months

• The rate of all-cause death

  3, 6, 12, 24, 36, 48 months

Other Outcomes (2)

• Evaluation of short-term procedural safety endpoints

  Within 48 hours from the procedure

• Evaluation of mid- and long-term procedural safety outcomes

  3 and 12 months

Study Arms (3)

PVI+LAAO

EXPERIMENTAL

80 patients

Procedure: PVI + LAAO, single stage

LAAO

EXPERIMENTAL

80 patients

Procedure: LAAO

NOAC

ACTIVE COMPARATOR

80 patients

Drug: NOAC

Interventions

LAAO PROCEDURE

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.

LAAO

NOAC DRUG

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.

NOAC

PVI + LAAO, single stage PROCEDURE

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.

PVI+LAAO

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pomeranian Medical University Szczecin: collaborator
• American Heart of Poland: collaborator
• Leszek Giec Upper-Silesian Medical Centre: collaborator
• Medical University of Silesia: lead
• Medical University of Lodz: collaborator
• Silesian Centre for Heart Diseases: collaborator

Study Sites (2)

Upper-Silesian Medical Center

Katowice, Upper Silesia, 40-635, Poland

RECRUITING

Silesian Center for Heart Disease

Zabrze, Upper Silesia, 41-800, Poland

RECRUITING

Related Publications (1)

• Wybraniec MT, Hoffmann A, Bochenek T, Lelek M, Wita M, Szydlo K, Lasek-Bal A, Gasior M, Kalarus Z, Ptaszynski P, Kazmierczak J, Mizia-Stec K, Wita K. Single-stage pulmonary vein isolation combined with percutaneous implantation of left atrial appendage occluder in patients with recent onset ischemic stroke and atrial fibrillation (PILOS-AF): A study protocol of randomized controlled trial. Cardiol J. 2025;32(4):416-424. doi: 10.5603/cj.104167. Epub 2025 Jun 3. No abstract available.

  PMID: 40459054 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Ischemic Stroke; Atrial Fibrillation

Interventions

N(4)-oleylcytosine arabinoside

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Maciej T. Wybraniec, MD, PhD, Professor

  Medical University of Silesia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maciej T. Wybraniec, MD, PhD, Professor

CONTACT

+48324796065; mwybraniec@sum.edu.pl

Krystian Wita, MD, PhD, Professor

CONTACT

+48323598953; dl@gcm.pl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 19, 2024
• Study Start: October 31, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2)