Efficacy and Safety of Radiofrequency Renal Denervation in Drug Resistant Hypertension

Study Overview
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Brief Summary
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Single-center, single group study of the efficacy and safety of transcatheter renal denervation for treatment of patients with essential hypertension uncontrolled despite combined pharmacotherapy including 3 or more hypotensive drugs one of which is a diuretic. Bilateral transcatheter renal denervation will be performed on the top of existed pharmacotherapy. Change in blood pressure (BP), left ventricle (LV) mass, carotid artery thickness, renal artery blood flow and renal function, will be assessed at 6 and 12 months of follow-up.

Official Title
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Study of Efficacy and Safety of Radiofrequency Sympathetic Renal Denervation for Treatment of Drug Resistant Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Procedure: Bilateral radiofrequency sympathetic renal denervation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 80 years at time of randomization Informed consent Treatment with full doses of 3 or more anti-hypertensive medications of different classes, of which one is a diuretic. Office Systolic BP (SBP) ≥ 160 mmHg or Diastolic BP (DBP) ≥ 100 mmHg Exclusion Criteria: An estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73 m2 Ambulatory Blood Pressure Monitoring (ABPM) 24 hour average SBP < 135 mmHg or DBP < 85 mmHg Symptomatic(secondary) hypertension Severe renal artery stenosis or renal arteries abnormalities Individual is pregnant, nursing or planning to be pregnant Severe hepatic dysfunction Any other clinically important renal, hematological, metabolic, neurological, gastrointestinal, hepatic or pulmonary disorders or dysfunctions preventing study participation (investigator's assessment)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Renal denervation<br>All eligible patients undergo bilateral radiofrequency sympathetic renal denervation using endocardial ablation system: after standard renal angiography using femoral access a small size endocardial ablation catheter (5-6 F, 4 mm electrode) is inserted into renal artery and 4-8 point ablations are performed consecutively from distal part to aorta with 3-4 mm step and 90 degrees rotation on the upper, lower, front and back aspects of the artery to get circumferential coverage, then the procedure is repeated on the other side. | Procedure: Bilateral radiofrequency sympathetic renal denervation<br>* Bilateral radiofrequency sympathetic renal denervation is performed as percutaneous transluminal radiofrequency (RF) ablation of neural pathways in the renal artery walls and surrounding tissue using standard equipment for RF ablation of cardiac electrical pathways<br>* Other names: Percutaneous radiofrequency ablation of renal nerves;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Office Systolic BP |  | from baseline to 12 months | 
| Number of Serious Adverse Events | A number of first occurrences (within the study period) of any of the following: death, end-stage renal disease, an embolic event resulting in end-organ damage, major bleeding event, renal artery thrombosis, new renal artery stenosis, other serious cardiovascular complications if their relation to the study treatment is assessed at least as possible. | from baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Office Diastolic BP |  | from baseline to 12 months | 
| Change in Mean 24-h Systolic BP |  | from baseline to 12 months | 
| Change in Mean 24-h Diastolic BP |  | from baseline to 12 months | 
| Change in Office Systolic BP |  | from baseline to 6 month | 
| Change in Office Diastolic BP |  | from baseline to 6 month | 
| Change in Mean 24-h Systolic BP |  | from baseline to 6 months | 
| Change in Mean 24-h Diastolic BP |  | from baseline to 6 months | 
| Change in Echocardiographic Left Ventricular Mass |  | from baseline to 6 months | 
| Change in Echocardiographic Left Ventricular Mass |  | from baseline to 12 months | 
| Change in Mean Daytime Systolic BP |  | from baseline to 6 months | 
| Change in Mean Daytime Diastolic BP |  | from baseline to 6 months | 
| Change in Mean Daytime Systolic BP |  | from baseline to 12 months | 
| Change in Mean Daytime Diastolic BP |  | from baseline to 12 months | 
| Change in Mean Nighttime Systolic BP |  | from baseline to 6 months | 
| Change in Mean Nighttime Diastolic BP |  | from baseline to 6 months | 
| Change in Mean Nighttime Systolic BP |  | from baseline to 12 months | 
| Change in Mean Nighttime Diastolic BP |  | from baseline to 12 months | 
| Change in Mean Nighttime Systolic BP Dipping | Mean nighttime BP dipping is a relative difference: absolute difference between mean daytime and mean nighttime BP values divided by mean daytime BP value | from baseline to 6 months | 
| Change in Mean Nighttime Diastolic BP Dipping | Mean nighttime BP dipping is a relative difference: absolute difference between mean daytime and mean nighttime BP values divided by mean daytime BP value | from baseline to 6 months | 
| Change in Mean Nighttime Systolic BP Dipping | Mean nighttime BP dipping is a relative difference: absolute difference between mean daytime and mean nighttime BP values divided by mean daytime BP value | from baseline to 12 months | 
| Change in Mean Nighttime Diastolic BP Dipping | Mean nighttime BP dipping is a relative difference: absolute difference between mean daytime and mean nighttime BP values divided by mean daytime BP value | from baseline to 12 months | 
| Change in Daytime Systolic BP Variability | daytime/nighttime BP variability is a standard deviation of BP values measured respectively during daytime/nighttime periods in course of ambulatory BP monitoring (ABPM) | from baseline to 12 months | 
| Change in Daytime Diastolic BP Variability | daytime/nighttime BP variability is a standard deviation of BP values measured respectively during daytime/nighttime periods in course of ambulatory BP monitoring | from baseline to 12 months | 
| Change in Nighttime Systolic BP Variability | daytime/nighttime BP variability is a standard deviation of BP values measured respectively during daytime/nighttime periods in course of ambulatory BP monitoring | from baseline to 12 months | 
| Change in Nighttime Diastolic BP Variability | daytime/nighttime BP variability is a standard deviation of BP values measured respectively during daytime/nighttime periods in course of ambulatory BP monitoring | from baseline to 12 months | 
| Change in Daytime Systolic BP Variability | daytime/nighttime BP variability is a standard deviation of BP values measured respectively during daytime/nighttime periods in course of ambulatory BP monitoring | from baseline to 6 months | 
| Change in Daytime Diastolic BP Variability | daytime/nighttime BP variability is a standard deviation of BP values measured respectively during daytime/nighttime periods in course of ambulatory BP monitoring | from baseline to 6 months | 
| Change in Nighttime Systolic BP Variability | daytime/nighttime BP variability is a standard deviation of BP values measured respectively during daytime/nighttime periods in course of ambulatory BP monitoring | from baseline to 6 months | 
| Change in Nighttime Diastolic BP Variability | daytime/nighttime BP variability is a standard deviation of BP values measured respectively during daytime/nighttime periods in course of ambulatory BP monitoring | from baseline to 6 months | 
| Change in Serum Creatinine |  | from baseline to 1 week | 
| Change in Serum Creatinine |  | from baseline to 6 months | 
| Change in Serum Creatinine |  | from baseline to 12 months | 
| Change in Casual Proteinuria | Change of protein concentration in morning urine sample | from baseline to 1 week | 
| Change in Casual Proteinuria | Change of protein concentration in morning urine sample | from baseline to 6 months | 
| Change in Casual Proteinuria | Change of protein concentration in morning urine sample | from baseline to 12 months | 
| Change in Specific Gravity of Urine | Change of specific gravity of morning urine sample | from baseline to 1 week | 
| Change in Specific Gravity of Urine | Change of specific gravity of morning urine sample | from baseline to 6 months | 
| Change in Specific Gravity of Urine | Change of specific gravity of morning urine sample | from baseline to 12 months | 
| Change in Renal Resistive Index Measured by Doppler Flowmetry in Left Main Renal Artery | Resistive index calculated as relative difference between assessed by ultrasound Doppler maximal and minimal blood flow velocities, i.e. absolute difference between maximal and minimal blood flow velocities divided by maximal flow velocity | from baseline to 6 months | 
| Change in Renal Resistive Index Measured by Doppler Flowmetry in Right Main Renal Artery | Resistive index calculated as relative difference between assessed by ultrasound Doppler maximal and minimal blood flow velocities, i.e. absolute difference between maximal and minimal blood flow velocities divided by maximal flow velocity | from baseline to 6 months | 
| Change in Resistive Index Measured by Renal Doppler Flowmetry in Left Main Renal Artery | Resistive index calculated as relative difference between assessed by ultrasound Doppler maximal and minimal blood flow velocities, i.e. absolute difference between maximal and minimal blood flow velocities divided by maximal flow velocity | from baseline to 12 months | 
| Change in Resistive Index Measured by Renal Doppler Flowmetry in Right Main Renal Artery | Resistive index calculated as relative difference between assessed by ultrasound Doppler maximal and minimal blood flow velocities, i.e. absolute difference between maximal and minimal blood flow velocities divided by maximal flow velocity | from baseline to 12 months | 
| Change in Ultrasound Intima Media Thickness of Carotid Artery |  | from baseline to 6 months | 
| Change in Ultrasound Intima Media Thickness of Carotid Artery |  | from baseline to 12 months | 
| Change in Arterial Stiffness | Change of cardio-ankle vascular index(CAVI) assessed by vascular screening device VaSera VS1000 (name of the model) | from baseline to 12 months | 
| Change in Arterial Stiffness | Change of cardio-ankle vascular index(CAVI) assessed by vascular screening device VaSera VS1000 | from baseline to 6 months | 
| Change in Morning Surge of BP |  | from baseline to 12 months | 
| Change in Morning Surge of BP |  | from baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Radiofrequency Catheter Ablation, Renal Artery, Sympathetic Nerve Block