Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension

Study Overview
=================
Brief Summary
-----------------
To demonstrate that non-invasive renal denervation is safe and shows a net difference in blood pressure reduction when compared to sham in subjects with uncontrolled hypertension.

Detailed Description
-----------------
This study is a sham controlled, double blind study of subjects with uncontrolled hypertension consisting of two arms, sham and therapy. Bilateral renal denervation will be performed non-invasively using the Kona Medical Surround Sound System which delivers focused ultrasound therapy to ablate the nerves surrounding the renal artery utilizing real time ultrasound for targeting and tracking.

Official Title
-----------------
Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Device: Investigational Therapy (Surround Sound)
* Device: Sham Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is at least 18 years of age and no more than 90 years of age Average SBP ≥ 160 mmHg 24 hour average ABPM daytime SBP ≥ 135 mmHg. No medication changes for a minimum of 1 months prior to screening. At minimum, subject must be on at least three antihypertensive medications, with one being a diuretic, and each must meet one or more of the following full dose criteria: Highest labeled dose according to medication's labeling; Highest usual dose per clinical guidelines JNC-7; Highest tolerated dose; and/or Highest appropriate dose for the subject per the PI's clinical judgment. Subject has two functioning kidneys. Subject has an eGFR value of ≥ 30 ml/min/1.73 m² (MDRD formula). Exclusion Criteria: Subject has any secondary cause of hypertension Subject has evidence of clinically significant renal artery stenosis as determined by flow rate, velocity and Doppler analysis on ultrasound Subject has kidney stones that are of a size and location that are determined at discretion of the investigator to potentially interfere with treatment Subject has a history of intra-abdominal surgery within the past six months Subject has heterogeneities in the kidney such as large cysts or tumors that are determined at discretion of the investigator to potentially interfere with treatment. Stenotic valvular heart disease for which BP reduction would be hazardous as determined by referring physician. MI, unstable angina, or CVA in the prior 6 months. Known severe primary pulmonary HTN Subject has a history of myocardial infarction, unstable angina pectoris, or cerebrovascular accident within the last six months. Subject has hemodynamically significant valvular heart disease. Subject has BMI over 40 km/m^2 Subject has a target treatment depth over 13 cm. Subject has anatomy that precludes treatment with the Kona Medical Surround Sound System. Subject is pregnant, nursing, or intends to become pregnant during the trial period. Subject is currently enrolled in other potentially confounding research. Subject has any condition that, at the discretion of the investigator, would preclude participation in the trial. Subject is unable, or unwilling, to comply with the protocol-required follow-up schedule

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational Therapy (Surround Sound)<br>Investigational Therapy using external focused ultrasound | Device: Investigational Therapy (Surround Sound)<br> <br> |
| Sham Comparator: Sham Control<br>Blinded Sham Control Arm | Device: Sham Control<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety at 6 weeks follow-up | Safety will be assessed by incidence of Major Adverse Events (MAE), defined as a composite of the following events at 6-weeks follow-up. All cause mortality; End-stage Renal Disease defined as eGFR < 15 ml/min or need for renal replacement therapy Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications as assessed by toxicological and other medical analyses and testing. OR - New renal artery stenosis > 70% confirmed by angiography within 6 months of randomization | 6 weeks | 
| Change in OBP | Change in Office Systolic Blood Pressure (OBP) as measured from screening visit one to the 6 month post randomization follow-up visit. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ABPM | Change in average 24-hour ambulatory blood pressure from screening to the 6 month follow-up visit | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypertension, Renal Denervation