A Feasibility Study to Evaluate the Effect of Concomitant Renal Denervation and Cardiac Ablation on AF Recurrence

Study Overview
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Brief Summary
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The purpose of this post market clinical investigation is to complete preliminary evaluation on whether or not concomitant renal denervation with the EnligHTN™ Renal Denervation System and cardiac ablation will result in improved outcomes as compared to ablation alone in patients with uncontrolled hypertension being treated for Atrial Fibrillation

Detailed Description
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This is a post market, prospective, multicenter, 2:1 randomized study of the EnligHTN™ Renal Denervation System in conjunction with atrial fibrillation ablation. Up to one hundred subjects with paroxysmal or persistent atrial fibrillation and uncontrolled hypertension will be enrolled in the study. All subjects will undergo cardiac ablation for the treatment of atrial fibrillation. Per the 2:1 randomization, a minimum of 50 or 2/3 of the total patient cohort will also undergo renal artery ablation. Subjects will be followed up to years (2) years post procedure.

Official Title
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A Feasibility Study to Evaluate the Effect of Concomitant Renal Denervation and Cardiac Ablation on AF Recurrence

Conditions
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Persistent Atrial Fibrillation, Paroxysmal Atrial Fibrillation, Hypertension

Intervention / Treatment
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* Device: Renal Artery Ablation
* Device: Cardiac Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥ 18 years of age at time of consent Subject must be able and willing to provide written informed consent Subject must be able and willing to comply with the required follow-up schedule Subject is a candidate for catheter ablation for the treatment of paroxysmal or persistent atrial fibrillation as per the hospital standard of care Subject has office Systolic Blood Pressure ≥ 140 mmHg at baseline visit Subject has a daytime mean Systolic Ambulatory Blood Pressure > 135 mmHg within 90 days prior to procedure Subject has established hypertension (diagnosed ≥12 month prior to baseline) and is taking >3 anti-hypertensive medications, including 1 diuretic Subject has been on a stable unchanged anti-hypertensive medication regimen for a minimum of 4 weeks prior to the ablation procedure Exclusion Criteria: Subject has long standing atrial fibrillation Subject has had a previous ablation for atrial fibrillation Subject has had a previous renal denervation procedure Subject has had a CABG procedure within the last 180 days (six months) Subject has a left atrial thrombus Subject has a contraindication to anticoagulation (i.e. heparin or warfarin) Subject has unstable angina Subject has had a myocardial infarction within the previous two months Subject has a left ventricular ejection fraction (LVEF) <40% as determined by pre-procedure TTE Subject has significant renovascular abnormalities such as renal artery stenosis > 30% Subject has undergone prior renal angioplasty, renal denervation, indwelling renal stents, and/or abdominal aortic stent grafts Subject has hemodynamically significant valvular heart disease as determined by study investigator Subject has a life expectancy less than 12 months, as determined by the study investigator Subject is participating in another clinical study which has the potential to impact his/her hypertension or atrial fibrillation management (pharmaceutical/device/homeopathic) Subject is pregnant, nursing, or of childbearing potential and is not using adequate contraceptive methods Subject has active systemic infection Subject has renal arteries < 4 mm in diameter Subject has an estimated GFR <45 mL/min per 1.73 m2 using the Modification of Diet in Renal Disease (MDRD) formula Subject had a renal transplant or is awaiting a renal transplant Subject has blood clotting or bleeding abnormalities Subject has secondary arterial hypertension

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cardiac ablation + renal artery ablation<br>Renal artery ablation with the EnligHTN™ Renal Denervation System | Device: Renal Artery Ablation<br>* Renal artery denervation using the EnligHTN™ Renal Denervation System<br>Device: Cardiac Ablation<br>* Safire BLU™ Duo or Therapy Cool Path Duo Irrigated Ablation Catheter or Therapy Cool Flex Irrigated Ablation Catheter EnSite Velocity System Agilis NxT Guiding Introducer<br>|
| Active Comparator: Cardiac ablation<br>Cardiac ablation | Device: Cardiac Ablation<br>* Safire BLU™ Duo or Therapy Cool Path Duo Irrigated Ablation Catheter or Therapy Cool Flex Irrigated Ablation Catheter EnSite Velocity System Agilis NxT Guiding Introducer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Freedom From Atrial Fibrillation at 12 Month | The freedom from atrial fibrillation was assessed based on electrocardiographic data during nine months following the blanking period including the one week recording coinciding with the 12 month follow-up visit (9 months following the 3 month blanking period). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiac Events (MACE) | Major adverse cardiac events (MACE) were summarized as a percentage based on number of subjects at baseline for each group (RDN+AF group = 39, AF group = 22). | 7 days, 6 months, 12 months, and 24 months post procedure | 
| Percentage of Participants Who Experience Peri-procedural Events | Peri-procedural events within 30 days post procedure were summarized as a percentage based on the number of subjects at baseline for each group (RDN+AF group= 39, AF group=22) | 30 days post procedure | 
| Assessment of Renovascular Safety as Measured by New Renal Artery Stenosis or Aneurysm at the Site of Ablation | Renovascular safety (new renal artery stenosis or aneurysm) was summarized as a percentage based on the number of subjects at baseline for each group (RDN+AF group= 39, AF group=22). | 6 months and 12 months post procedure | 
| Renal Function Change Based on Estimated Glomerular Filtration Rate (eGFR) (Renal Denervation Group Only) at 6 Months |  | Baseline and 6 months | 
| Renal Function Change Based on eGFR (Renal Denervation Group Only) at 12 Months |  | Baseline and 12 months | 
| Recurrence of Atrial Fibrillation (AF) Based on Electrocardiographic Data up to 2 Years Following the Initial Cardiac Ablation Procedure. | Recurrence of AF was summarized as a percentage based on the number of subjects who underwent the procedure (RDN+AF group= 39, AF group=20) | 3 months, 6 months, 12 months, 24 months | 
| Percentage of Participants Achieving Office Systolic Blood Pressure < 140 mmHg |  | 6 months post procedure | 
| Change in Ambulatory Blood Pressure at 12 Months | Change in Ambulatory Blood Pressure was summarized based on subjects with available data at both time points (RDN+AF group= 22, AF group=14) | Baseline and 12 months post procedure | 
| Change in Ambulatory Blood Pressure at 24 Months | Change in Ambulatory Blood Pressure was summarized based on subjects with available data at both time points (RDN+AF group= 17, AF group=12) | Baseline and 24 months post procedure | 
| Change in Office Blood Pressure at 12 Months | Change in Office Blood Pressure was summarized based on subjects with available data at both time points (RDN+AF group= 33, AF group=15) | Baseline and 12 months post procedure | 
| Change in Office Blood Pressure at 24 Months | Change in Office Blood Pressure was summarized based on subjects with available data at both time points (RDN+AF group= 29, AF group=16). | Baseline and 24 months post procedure |