Ultrasound-Based Renal Sympathetic Denervation as Adjunctive Upstream Therapy During Atrial Fibrillation Ablation

Study Overview
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Brief Summary
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The purpose of the ULTRA-HFIB Pilot is to determine the role of adjunctive renal denervation (RDN) in the prevention of Atrial Fibrillation (AF) recurrence in patients scheduled for an AF ablation procedure. Patients will be randomized to either i) AF ablation (Control) or ii) AF ablation + renal sympathetic denervation (Intervention).

Detailed Description
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The purpose of the ULTRA-HFIB Pilot is to determine the role of adjunctive renal denervation (RDN) in the prevention of AF recurrence in patients scheduled for an AF ablation procedure. Patients will be randomized to either i) AF ablation (Control) or ii) AF ablation + renal sympathetic denervation (Intervention). This is a prospective, controlled, single-blind, randomized trial. The pilot study will be conducted in up to 11 clinical sites in the United States and Europe.

Official Title
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Ultrasound-Based Renal Sympathetic Denervation as Adjunctive Upstream Therapy During Atrial Fibrillation Ablation: A Pilot Study

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Device: renal denervation
* Device: Catheter ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Planned for a first-ever AF ablation procedure (paroxysmal or persistent); (prior to randomization, a technically successful AF ablation procedure, defined as involving pulmonary vein isolation, as well as bidirectional block of any attempted anatomic lesion sets such as cavotricuspid isthmus line, roofline, mitral line and superior vena cava isolation must have been completed) History of hypertension and either: Documented history of SBP ≥ 160 or DBP ≥ 100 (Stage III), or Receiving ≥ 1 antihypertensive medication Willingness to adhere to study restrictions and comply with all post-procedural follow-up requirements Exclusion Criteria: (if any of the following are YES, subject is not eligible) Long-standing persistent AF (> 12 months) Individual with valvular AF or AF due to a reversible cause Prior left atrial catheter or surgical ablation for an atrial arrhythmia (before this index procedure) Prior left atrial surgery (such as mitral valve surgery or surgical ASD repair) Prior treatment with other devices for hypertension including but not limited to ROX Coupler, Mobius stent and/or the CVRx barostimulator device NYHA Class IV Congestive Heart Failure Individual has renal artery anatomy that is ineligible for treatment (as determined by intra-procedural renal angiography). This includes: Main renal artery diameter < 3.0 mm or > 8.0 mm Main renal artery length < 20 mm Presence of renal artery stenosis of any origin ≥ 30% Accessory arteries with diameter ≥ 2 mm and < 3.0 mm Calcification in renal arteries at locations where energy is to be delivered Prior renal denervation procedure Presence of abnormal kidney tumors Renal artery aneurysm Pre-existing renal stent or history of renal artery angioplasty Pre-existing aortic stent or history of aortic aneurysm Fibromuscular disease of the renal arteries Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter Individual has an estimated glomerular filtration rate (eGFR) of less than 40mL/min/1.73m2 Inability to undergo AF catheter ablation (e.g., presence of left atrial thrombus, contraindication to all anticoagulation) Individual with known allergy to contrast medium not amenable to treatment Life expectancy of < 1 year for any medical condition Individual has experienced a myocardial infarction, unstable angina, cerebrovascular accident, or heart failure admission within 3 months of screening visit Documented history of chronic active inflammatory bowel disorders such as Crohn's disease or ulcerative colitis Female participants who are pregnant or nursing Individual has known secondary hypertension Individual has a single functioning kidney (either congenitally or iatrogenically) Individual has a known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements Patients concurrently enrolled in any other investigational drug or device trial that would interfere with the conduction of this trial

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Catheter ablation + renal denervation<br>Catheter ablation + renal denervation | Device: renal denervation<br>* Renal denervation using the Paradise renal denervation system - a dedicated RDN catheter that delivers a circumferential ring of ablative ultrasound energy<br>Device: Catheter ablation<br>* Catheter ablation - one of the most common procedures performed by Cardiac Electrophysiologists for atrial fibrillation<br>|
| Active Comparator: Catheter ablation only<br>Catheter ablation | Device: Catheter ablation<br>* Catheter ablation - one of the most common procedures performed by Cardiac Electrophysiologists for atrial fibrillation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single-procedure freedom from AT/AF/AFL recurrence ≥ 30 seconds | Single-procedure freedom from AT/AF/AFL recurrence ≥ 30 seconds off Class I and III AADs (after the 90-day blanking period), defined by absence of any electrocardiographically documented AT/AF. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from AT/AF/AFL recurrence | Freedom from AT/AF/AFL recurrence through 12 months (excluding a 90-day blanking period from the initial ablation procedure) irrespective of AADs | 12 months | 
| Rate of procedural adverse events | Rate of procedural adverse events | 30 days | 
| The Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire | Quality of life instrument (AFEQT) is a 20-item disease-specific scale developed to capture subjective ratings of AF disease and treatment burden. Full range score from 0-100, with higher score indicating higher level of quality of life. | 12 months | 
| Change in office systolic blood pressure change from baseline to 12 months | Change in office systolic blood pressure change from baseline to 12 months | 12 months | 
| AF burden at 6 months | AF burden at 6 months | 6 months | 
| AF burden at 12 months | AF burden at 12 months | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal denervation, atrial fibrillation, cardiology, electrophysiology