Pulmonary Vein Isolation Using Stereotactic Radiotherapy System for the Treatment of Refractory Atrial Fibrillation

Study Overview
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Brief Summary
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The study aims to investigate the short-term (3 months) and intermediate-term (12 months) safety and preliminary efficacy of stereotactic radiotherapy for pulmonary vein isolation to treat refractory atrial fibrillation.

Detailed Description
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This is a single center, single arm, prospective and phase 1 clinical trial. Patients with refractory atrial fibrillation (AF) will receive single fraction stereotactic radiotherapy for pulmonary vein isolation. To minimize the potential risks associated with this innovative technique, the study has been designed in a stepwise dose escalation fashion under carefully observation by the investigators. The dose escalation is guided by 3+3 algorithm to ensure more patients will be spared dose limiting toxicities and more patients will be entered on the dose level than will be chosen as optimal dose of maximal effects. Low dosing levels with established safety profile will first be applied before administering higher dosing levels based on preclinical studies. Safety is the primary endpoint of the study. Safety will be assessed by incidence and evaluation of any serious adverse evens using CTCAE V5.0 criteria associated with the procedure through 90 days (short-term) and 12 months (intermediate term). Efficacy will be evaluated by assessing atrial fibrillation recurrence (for paroxysmal AF) or AF burden (for persistent AF) after 90 days of blank period until 12 months post-treatment.

Official Title
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Pulmonary Vein Isolation Using Stereotactic Radiotherapy System for the Treatment of Refractory Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Radiation: Stereotactic Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Paroxysmal or persistent atrial fibrillation. Age 55-89 Symptomatic, refractory to at least 3 antiarrhythmic drugs Failure from the previous catheter ablation of atrial fibrillation, or contraindicate /unwilling to undergo catheter ablation. Anticoagulation for at least 3 months if CHA2DS2-VASc 2 or more. Exclusion Criteria: With concomitant atrial flutter, WPW syndrome or supraventricular tachycardia. With sustained ventricular tachycardia. With sick sinus syndrome or atrioventricular block fulfilling the indication of permanent pacemaker implantation. Stroke or myocardial infarction within 8 weeks. Uncontrolled heart failure or unstable angina pectoris. Severe structral heart diseases. Severe pulmonary hypertension. Uncontrolled hypertension. Severe respiratory disease. Esophageal ulcer. Intracardiac thrombus by TEE. Pregnancy or have a preganancy plan. Others.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: stereotactic body radiotherapy (SBRT)<br>Noninvasive SBRT will be delivered in a single fraction to electrical isolate the pulmonary veins under CT-guidance. | Radiation: Stereotactic Radiotherapy<br>* Stereotactic radiotherapy targets on the pulmonary vein ostium aiming to achieve pulmonary vein electrial isolation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90 days adverse events by CTCA5 | Safety will be assessed by incidence and evaluation of any adverse events using CTCA5 V5.0 criteria that are related to the procedure | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12 months adverse events by CTCA5 | Safety will be assessed by incidence and evaluation of any adverse events using CTCA5 V5.0 criteria that are related to the procedure | 12 months | 
| Recurrence of atrial fibrillation (for paroxysmal atrial fibrillation) | Recurrence of atrial fibrillation after 90 days blanking period post-treatment | 90 days to 12 months | 
| Atrial fibrillation burden reduction (for persistent atrial fibrillation) | Atrial fibriilation burden reduction after 90 days blanking period post-treatment | 90 days to 12 months | 
| All-cause motality | Motality due to any reason | 12 months | 
| Quality of life improvement | Quality of life after the procedure evaluated by the questionnaire | 3 month, 6 month and 12 month |