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.

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.

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