Distal Renal Denervation

Study Overview
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Brief Summary
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Objective of this study is to evaluate whether a distal mode of endovascular renal denervation with the treatment performed primarily in segmental branches of renal artery is more effective than conventional mode of the intervention with the treatment equally distributed within its main trunk for the treatment of drug-resistant hypertension.

Detailed Description
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Recent spectacular failure of renal denervation (RDN) therapy in SymplicityHTN-3 trial in fact might be easily predicted from the very beginning. Conventional RDN done as 4-6 point treatments equally distributed within main trunk of renal artery (RA) may only be effective if renal plexus tightly surrounds the artery throughout its whole course with equal longitudinal and circumferential density of the nerve fibers. While this idea itself is unnaturally idealistic also a number of surgical studies demonstrated that proximally majority of renal nerves go at a distance from RA obliquely to its course and join the artery mainly in its distal part (fan-shaped renal plexus with wide base directed toward aorta and apex converging to renal gate). We developed a distal mode of RDN targeting segmental branches of RA and conducted a single-center double-blind randomized controlled parallel group study to compare its efficacy and safety to those of conventional RDN in patients with drug-resistant hypertension.

Official Title
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Anatomically Optimized Distal Renal Denervation for Treatment of Resistant Hypertension

Conditions
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Hypertension, Resistant to Conventional Therapy

Intervention / Treatment
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* Procedure: Distal renal denervation
* Procedure: Conventional renal denervation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: systolic BP is equal or greater than 160 mmHg or diastolic BP is equal or greater than 100 mmHg, stable (>3 months) treatment with full doses of at least 3 antihypertensive drugs including a diuretic, given written informed consent Exclusion Criteria: secondary hypertension 24h-mean systolic BP <135 mmHg, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, extended disease of renal artery, any other clinically important disorders/comorbidities significantly increasing risk of endovascular intervention (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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Distal renal denervation<br>Endovascular denervation of segmental branches of renal artery | Procedure: Distal renal denervation<br>* Percutaneous endovascular intervention when catheter-based electrode (Symplicity Flex; Medtronic, Inc.) is used for stepwise radiofrequency energy delivery to segmental branches of the renal artery in a number of points distributed along the length and circumference of the vessels in order to ablate renal nerve plexus<br>|
| Active Comparator: Conventional renal denervation<br>Endovascular denervation of main trunk of renal artery | Procedure: Conventional renal denervation<br>* Percutaneous endovascular intervention when catheter-based electrode (Symplicity Flex; Medtronic, Inc.) is used for stepwise radiofrequency energy delivery to the main trunk of the renal artery in a number of points equally distributed along its length and circumference in order to ablate renal nerve plexus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of 24h-mean Systolic BP Assessed by Ambulatory Blood Pressure Monitoring (ABPM) |  | From baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events |  | From baseline to 6 months | 
| Number of Adverse Events |  | From baseline to 12 months | 
| Changes of Arterial Resistance Index Measured by Doppler Flowmetry in the Right Segmental Renal Arteries | Resistance index is calculated as the relative difference between a peak systolic and end diastolic blood flow velocities assessed by ultrasound Doppler flowmetry | From baseline to 6 months | 
| Changes of Arterial Resistance Index Measured by Doppler Flowmetry in the Left Segmental Renal Arteries | Resistance index calculated as the relative difference between a peak systolic and end diastolic blood flow velocities assessed by ultrasound Doppler flowmetry | From baseline to 6 months | 
| Changes of Serum Creatinine |  | From baseline to 6 months | 
| Changes of Serum Creatinine |  | From baseline to 12 months | 
| Changes of Estimated Glomerular Filtration Rate (eGFR) |  | From baseline to 6 months | 
| Changes of Estimated Glomerular Filtration Rate (eGFR) |  | From baseline to 12 months | 
| Changes of 24h-mean Diastolic BP |  | From baseline to 6 months | 
| Changes of 24h-mean Systolic BP |  | From baseline to 12 months | 
| Changes of 24h-mean Diastolic BP |  | From baseline to 12 months | 
| Changes of Office Systolic BP |  | From baseline to 6 months | 
| Changes of Office Systolic BP |  | From baseline to 12 months | 
| Changes of Office Diastolic BP |  | From baseline to 6 months | 
| Changes of Office Diastolic BP |  | From baseline to 12 months | 
| Changes of Daytime Systolic BP |  | From baseline to 6 months | 
| Changes of Daytime Mean Systolic BP |  | From baseline to 12 months | 
| Changes of Daytime Mean Diastolic BP |  | From baseline to 6 months | 
| Changes of Daytime Mean Diastolic BP |  | From baseline to 12 months | 
| Changes of Nighttime Mean Systolic BP |  | From baseline to 6 months | 
| Changes of Nighttime Mean Systolic BP |  | From baseline to 12 months | 
| Changes of Nighttime Mean Diastolic BP |  | From baseline to 6 months | 
| Changes of Nighttime Mean Diastolic BP |  | From baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Catheter Ablation, Renal Nerves