Renal Denervation for Uncontrolled Hypertension

Study Overview
=================
Brief Summary
-----------------
This is a study investigating the safety and usefulness of the Renal Denervation Procedure in reducing high blood pressure in people whose blood pressure is not adequately controlled despite already being treated with 2 blood pressure lowering drugs. This study is designed to compare the effects renal denervation to a usual care group.

Detailed Description
-----------------
This is a phase 4 randomised control trial of renal denervation for the treatment of uncontrolled hypertension. Previous studies have shown that the renal denervation procedure is safe and effective in reducing blood pressure. A total of 100 participants with uncontrolled blood pressure, treated with two blood pressure lowering medications will be recruited into the study. Patients will be assigned to one of two groups. Participants in Group 1 will be assigned to undergo the renal denervation procedure. Participants in group 2 will undergo usual care, receiving additional antihypertensive medication in an attempt to reach blood pressure targets. The duration of this study is 36 months.

Official Title
-----------------
Renal Denervation for Uncontrolled Hypertension

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

Intervention / Treatment
-----------------
* Device: Renal Denervation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BP ≥140/90 mmHg (or ≥130/80 mmHg for patients with diabetes) concurrent treatment with 2 anti-hypertensive drugs Exclusion Criteria: renal artery anatomy ineligible for treatment eGFR <15mL/min/1.73m2 (using MDRD formula) individual has had myocardial infarction, unstable angina or cerebrovascular accident within 6 months of screening visit female participants of child bearing potential must have negative pregnancy test prior to treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual care<br>participants randomised to the usual care group will receive additional antihypertensive medication in an attempt to achieve blood pressure targets | |
| Experimental: Renal Denervation Group<br>participants randomised to undergo the renal denervation procedure | Device: Renal Denervation<br>* Renal Denervation Catheter<br>* Other names: Symplicity Renal Denervation Catheter;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood pressure control | percentage of patients who achieve BP target at 6 months post intervention | 6 months post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of drugs required to reach target blood pressure | number of drugs required to reach target blood pressure | baseline to 6 months | 
| time to achieve blood pressure target | time to achieve blood pressure target | baseline to 6 months | 
| change in sympathetic nerve activity | changes in muscle sympathetic nerve activity (MSNA), renal and whole body Noradrenaline (NA) spillover | baseline to 6 months | 
| Change in left ventricular function | Change in left Ventricular ejection fraction, diastolic filling | baseline to 6 months | 
| Change in Quality of Life | Change in Quality of life as assessed be relevant questionnaires | baseline to 6 months | 
| Change in Serum Biochemistry | Plasma Renin Activity, aldosterone levels, estimated Glomerular Filtration Rate(eGFR), inflammatory markers, fasting glucose, fasting insulin, C-peptide, Homeostasis Model Assessment (HOMA) index, Lipid profile | baseline to 6 months | 
| Change in markers of arterial stiffness | Change in markers of arterial stiffness as assessed by Augmentation Index (AI) and Pulse Wave Velocity (PWV) | baseline to 6 months | 
| Change in left ventricular structure | Change in left ventricular mass index | baseline to 6 months | 
| Change in Urine Biochemistry | Urinary albumin creatinine ratio (UACR), 24 hour urinary creatinine clearance, sodium | baseline to 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
renal denervation, blood pressure, cardiovascular risk, target organ damage, sympathetic activity