Renal Denervation in Hypertension

Study Overview
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Brief Summary
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The DENER-HTN study is a, multicenter, prospective, open, randomized, controlled study of the effectiveness and costs of renal denervation in addition to standardized medical treatment compared to medical treatment alone in subjects with resistant hypertension. Bilateral renal denervation will be performed using the Symplicity Catheter - a percutaneous system that delivers radiofrequency (RF) energy through the luminal surface of the renal artery.

Detailed Description
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The DENER-HTN study is a, multicenter, prospective, open, randomized, controlled study of the efficacy and cost-effectiveness of renal denervation plus standardized optimal antihypertensive treatment compared to standardized optimal antihypertensive treatment alone in patients with proven resistant hypertension. Patients with essential resistant hypertension will first enter a 4-week run-in period during which they will receive a standardized triple combination therapy (diuretic+ ACE inhibitor+ CCB at maximal dose). After 4 weeks of standardized triple therapy patients will be randomized to renal denervation + optimal antihypertensive treatment compared to standardized optimal antihypertensive treatment if daytime ambulatory BP remains ≥ 135 and/or 85 mmHg. Bilateral renal denervation will be performed using the Symplicity Catheter (Medtronic ®) - a percutaneous system that delivers radiofrequency (RF) energy through the luminal surface of the renal artery. Study amendment: Extended follow-up of 48 months for all randomized patients.

Official Title
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Renal Denervation in Patients With Resistant Hypertension

Conditions
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Hypertension, Resistant to Conventional Therapy, Renal Denervation

Intervention / Treatment
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* Procedure: renal denervation and optimized medication regimen
* Procedure: optimized medication regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individual is more than 18 and less than 75 years old at time of randomization Essential hypertension diagnosed during a complete work-up within the past 2 years Office blood pressure ≥140 and/or 90 mmHg despite a stable medication regimen including full tolerated doses of 3 or more anti-hypertensive medications of different classes, including a diuretic 2 functional kidneys sizing ≥ 90 mm; eGFR ≥ 40 mL/min/1.73m² (MDRD formula) Suitable renal anatomy compatible with the endovascular denervation procedure Signed Informed consent Confirmed resistant hypertension defined by diurnal ambulatory blood pressure measurement ≥ 135 and/or 85 mmHg after 4 week standardized triple antihypertensive treatment Exclusion Criteria: Patients with an estimated glomerular filtration rate (eGFR) of less than 40 mL/min/1.73 m2 Patients with secondary hypertension Kaliemia ≥ 6mmol/L Patient with single functioning kidney Patient with contrast media allergy Patient with any implantable device incompatible with radiofrequency energy delivery Patient with contra-indication to the anti-hypertensive standardized medication regimen Patient with transient or fixed cerebral ischemia within 3 months before inclusion Patient with myocardial infarction, unstable angina pectoris, coronary bypass or percutaneous angioplasty within 3 months before inclusion Patient with type 1 diabetes mellitus Patient with malignancy within the 5 past years Patient with atrial fibrillation and/or a brachial circumference of ≥ 42cm

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Renal denervation<br> | Procedure: renal denervation and optimized medication regimen<br>* Patients are treated with the renal denervation plus a standardized optimal antihypertensive treatment which is adapted every month starting two month after randomization on the basis of home BP monitoring results at follow-up visits.<br>* Other names: TMAOS + DR;|
| Other: optimized medication regimen<br>optimized medication regimen | Procedure: optimized medication regimen<br>* Patients are treated with a standardized optimal antihypertensive treatment which is adapted every month starting two month after randomization on the basis of home BP monitoring results at follow-up visits.<br>* Other names: TMAOS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean diurnal systolic blood pressure assessed by ABPM |  | Baseline to 6 months | 
| Cost-effectiveness evaluation |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antihypertensive medication score |  | baseline to 15 months | 
| Adverse events of renal denervation |  | baseline to 48 months | 
| Detailed analysis of blood pressure |  | baseline to 15 months | 
| Change in average 24-hour and nighttime Systolic Blood Pressure by ambulatory blood pressure monitoring |  | baseline to 15 months | 
| Change in average 24-hour, daytime and nighttime diastolic Blood Pressure, pulse pressure and heart rate by ambulatory blood pressure monitoring |  | baseline to 15 months | 
| Change in Systolic/diastolic Blood Pressure by home blood pressure monitoring |  | baseline to 15 months | 
| Change in office Systolic/diastolic Blood Pressure |  | baseline to 15 months | 
| Adherence to antihypertensive Medication |  | baseline to 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistant hypertension, Renal denervation, Standardized medication regimen, Endovascular, Primary hypertension, Cardiovascular diseases, Vascular diseases