Adjunctive Renal Denervation in the Treatment of Atrial Fibrillation

Study Overview
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Brief Summary
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The objective of the H-FIB trial is to determine the role of renal sympathetic denervation in the prevention of Atrial Fibrillation (AF) recurrence in patients with hypertension for whom a catheter-based AF ablation procedure is planned. Patients will be randomized to either AF catheter ablation (usual therapy) or AF catheter ablation plus renal sympathetic denervation.

Detailed Description
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The purpose of this study is to examine the potential additional benefit of performing renal sympathetic denervation at the same time as an AF ablation procedure, in order to improve the long-term success of the AF procedure. To take part in this study, you must meet all study requirements. Screening visit tests and procedures such as a physical exam, blood pressure, review of medical history, blood sample, and a Transthoracic Echocardiogram (TTE) are done to see if you are eligible to be in the study. Patients who qualify for the study and provide consent will undergo catheter ablation for AF. Very thin electrode catheters, similar to long wires, will be inserted into blood vessels in the groin. Using the ablation catheter, we will ablate or damage the tissue adjacent to your pulmonary veins that is not behaving normally. Immediately following the catheter ablation, patients will undergo a renal angiogram in order to assess suitability for catheter-based renal sympathetic denervation. A renal angiogram is an x-ray study of the blood vessels in the kidney to evaluate for blockage, and abnormalities that could be affecting the blood supply to the kidney. It is performed by injecting contrast dye through a catheter (a tiny tube) into the blood vessels of the kidney.

Official Title
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Adjunctive Renal Denervation to Modify Hypertension and Sympathetic Tone as Upstream Therapy in the Treatment of Atrial Fibrillation

Conditions
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Uncontrolled Hypertension, Atrial Fibrillation

Intervention / Treatment
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* Device: Boston Scientific Vessix Renal Denervation System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria Age ≥ 18 years of age History of AF (paroxysmal or persistent) and planned for a guideline-supported catheter ablation procedure History of significant hypertension (defined as SBP ≥160 mm Hg and/or DBP ≥100 mmHg) and receiving treatment with at least one anti-hypertensive medication OR Clinical History of hypertension and receiving treatment with at least two anti-hypertensive medications (specifically for blood pressure reduction). Renal vasculature is accessible as determined by intra-procedural renal angiography. Ability to understand the requirements of the study Willingness to adhere to study restrictions, comply with all post-procedural follow-up requirements and to sign informed consent Exclusion Criteria Inability to undergo AF catheter ablation (e.g., presence of a left atrial thrombus, contraindication to all anticoagulation) Prior left atrial ablation for an atrial arrhythmia (before this index procedure) Patients with NYHA class IV congestive heart failure Individual has known secondary hypertension Individual has renal artery anatomy that is ineligible for treatment including: Inability to access renal vasculature Main renal arteries < 3 mm in diameter or < 20 mm in length. Hemodynamically or anatomically significant renal artery abnormality or stenosis in either renal artery which, in the eyes of the operator, would interfere with safe cannulation of the renal artery or meets standards for surgical repair or interventional dilation. A history of prior renal artery intervention including balloon angioplasty or stenting that precludes a possibility of ablation treatment. Individual has an estimated glomerular filtration rate (eGFR) of less than 45mL/min/1.73m2, using the MDRD calculation. Individual has a single functioning kidney (either congenitally or iatrogenically). Individual is pregnant or nursing. Life expectancy <1 year for any medical condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Intervention arm<br>These subjects will undergo routine catheter ablation of atrial fibrillation PLUS renal sympathetic denervation with the Boston Scientific Vessix Renal Denervation System. | Device: Boston Scientific Vessix Renal Denervation System<br>* Renal sympathetic denervation is modulation of the nerves which run along the renal arteries (the renal sympathetic nerves) with radiofrequency energy. This is the same energy source used to perform your heart ablation. Boston Scientific Vessix Renal Denervation System, Boston Scientific, Inc., Quincy, Massachusetts<br>* Other names: denervation;|
| No Intervention: Control arm<br>These subjects will undergo routine catheter ablation of atrial fibrillation only. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-arrhythmic Drug (AAD)-Free Single-procedure Freedom From Atrial Fibrillation Recurrence | The primary endpoint of this study is anti-arrhythmic drug (AAD)-free single-procedure freedom from AF recurrence through 12 months (not including a 90 day blanking period). | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AAD-free Single-procedure Freedom From AF Recurrence | AAD-free single-procedure freedom from AF recurrence through 24 months (not-including recurrences within the first 90 days of the initial ablation procedure) | up to 24 months | 
| Freedom From AF Recurrence Despite Taking AADs | Freedom from AF recurrence through 24 months (not-including the pre-defined 90 day blanking period) despite taking AADs | up to 24 months | 
| Blood Pressure Control as Compared to Baseline | Blood pressure control between the two groups as compared to baseline at 6 months, 12 months and 24 months. | baseline, 6 months, 12 months, and 24 months | 
| Number of Participants With Major Adverse Cardiac Events (MACE) | Number of Participants with Major adverse cardiac events (MACE) defined as a non-weighted composite score of: death, stroke, CHF hospitalization, and clinically diagnosed thromboembolic events other than stroke and hemorrhage requiring transfusion within 12 months of randomization | within 12 months of randomization | 
| Number of Participants With Serious Adverse Events (SAE) | SAE-any experience that results in a fatality or is life threatening; results in significant or persistent disability; requires or prolongs hospitalization; results in congenital anomaly/birth defect; or represents other significant hazards or potentially serious harm to research subjects or others, in the opinion of the investigators. Important medical events that may not result in above may be considered a SAE when, based upon appropriate medical judgment, they may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed in this definition | up to 24 months | 
| Left Atrial (LA) Size | LA size by TTE at baseline and at 12 months | at baseline and at 12 months | 
| Ejection Fraction (EF) | Ejection fraction (EF) is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction. A normal heart's ejection fraction may be between 50 and 70 percent. | at baseline and at 12 months | 
| Number of Participants With Procedure Adverse Events | Causality will be defined as adverse events that, after careful medical evaluation, are considered with a high degree of certainty to be related to the intervention (AF ablation ± renal sympathetic denervation). | up to 24 months | 
| Number of Anti-hypertensive Medications | Total number of anti-hypertensive medications at study end, compared between the two treatment arms | baseline and 24 months | 
| Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT) | The change in quality of life (QoL) from baseline to 12 months as measured by AFEQT, a 20- item instrument. Full range from 0 to 100, with higher score indicates higher level of QoL. | baseline, 12 months and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal sympathetic denervation, renal catheter ablation, hypertension