Study of Catheter Based Renal Denervation Therapy in Hypertension

Study Overview
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Brief Summary
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The DEPART study end points are to provide conclusive evidence, using a randomized, double blinded, sham procedure controlled study design, that radiofrequency renal denervation: reduces daytime ambulatory blood pressure, improves nocturnal dipping in blood pressure at the ambulatory blood pressure recording.

Official Title
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DENERVATION OF RENAL SYMPATHETIC ACTIVITY AND HYPERTENSION STUDY

Conditions
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Resistant Hypertension, Renal Denervation, Ambulatory Blood Pressure, Renal Function

Intervention / Treatment
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* Procedure: Renal angiography followed by renal sympathetic denervation
* Procedure: Renal angiography alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: They have a mandatory > 3 antihypertensive medication therapy, including a thiazide or a loop diuretic (according to the patient's renal function, unless documented side-effects) and at least one attempt to treat with spironolactone, given at usual recommended dose since at least 8 weeks, before inclusion, A mandatory check list of secondary cause of hypertension has been excluded They succeed the pill count test. They have a mandatory ambulatory blood pressure monitoring before inclusion with at least 70% of valid readings during daytime (08:00 am 08:00 pm, using a sampling frequency of 20 minutes, only devices validated according to http://www.dableducational.org are permitted), where daytime ambulatory blood pressure of systolic and/or diastolic blood pressure exceeds 135 mmHg and/or 85 mmHg, respectively. Daytime ambulatory blood pressure of systolic and/or diastolic blood pressure below 135 mmHg and/or 85 mmHg, respectively, is acceptable for inclusion in the study if the patient takes four or more antihypertensive medication (3). Exclusion Criteria: Patients with an eGFR <30ml/min/m² are excluded, patients with known renal atherosclerotic lesions, previous procedures in the renal arteries, known unsuitable anatomy for the procedure, previous nephrectomy, contrast agent allergy, hyperthyroidia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Renal angiography followed by renal sympathetic denervation<br>Catheter based therapy for renal denervation using the Simplicity (TM) catheter (Ardian/Medtronic) | Procedure: Renal angiography followed by renal sympathetic denervation<br>* Radiofrequency catheter based therapy for renal denervation: Symplicity catheter will be advanced into the renal artery and connected to a radiofrequency generator. As previously described, four-to-six discrete, low-power radio frequency treatments will be applied along the length of both main renal arteries. At least four radiofrequency applications will be delivered in each renal artery, unless this is not feasible for anatomical reasons.<br>|
| Sham Comparator: Renal angiography alone<br>Renal selective angiography using standardized method: Local anesthesia of the femoral site to allow the placement of a 4-Fr sheath in the femoral artery. Using JR-4 or similar diagnostic catheter, a selective renal angiography will be realized. | Procedure: Renal angiography alone<br>* Procedure will start with a local anesthesia of the femoral site to allow the placement of a 4-Fr sheath in the femoral artery, which allows a minimal risk of bleeding to the patient. Using JR-4 or similar diagnostic catheter, a selective renal angiography will be realized.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glomerular filtration rate | Isotopic and 24h urine sample measure of glomerular filtration rate. | 6 month | 
| Ambulatory systolic and diastolic blood pressure | Ambulatory systolic and diastolic blood pressure measured on 24h ABPM device | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baroreflex sensitivity | Migroneugraphy recording of sympathetic nerve activity and testing of baroreflex sensitivity | 6 month | 
| Biological markers of acute kidney injury | Urine sample for NGAL, L-FABP and Cystatine C at baseline, H2, H6, 1, 3 and 6 months | baseline, H2, H6, 1, 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistant hypertension, Renal denervation, Ambulatory blood pressure, Renal function, Simplicity catheter, Sham procedure