Clinical trial NCT01570777: Renal Denervation in Hypertension
Official title: Renal Denervation in Patients With Resistant Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension, Resistant to Conventional Therapy
Renal Denervation
Keywords: Resistant hypertension
Renal denervation
Standardized medication regimen
Endovascular
Primary hypertension
Cardiovascular diseases
Vascular diseases
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2012-04-04
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean diurnal systolic blood pressure assessed by ABPM
timeFrame: Baseline to 6 months
measure: Cost-effectiveness evaluation
timeFrame: 1 year
Secondary outcomes:
measure: Antihypertensive medication score
timeFrame: baseline to 15 months
measure: Adverse events of renal denervation
timeFrame: baseline to 48 months
measure: Detailed analysis of blood pressure
timeFrame: baseline to 15 months
measure: Change in average 24-hour and nighttime Systolic Blood Pressure by ambulatory blood pressure monitoring
timeFrame: baseline to 15 months
measure: Change in average 24-hour, daytime and nighttime diastolic Blood Pressure, pulse pressure and heart rate by ambulatory blood pressure monitoring
timeFrame: baseline to 15 months
measure: Change in Systolic/diastolic Blood Pressure by home blood pressure monitoring
timeFrame: baseline to 15 months
measure: Change in office Systolic/diastolic Blood Pressure
timeFrame: baseline to 15 months
measure: Adherence to antihypertensive Medication
timeFrame: baseline to 15 months
Other outcomes:
Locations:
city: Paris
country: France
facility: CIC Hopital europeen george pompidou
Study officials:
affiliation: departement of interventional radiology
name: Marc SAPOVAL, PD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hamdidouche I, Gosse P, Cremer A, Lorthioir A, Delsart P, Courand PY, Denolle T, Halimi JM, Girerd X, Ormezzano O, Rossignol P, Pereira H, Azizi M; DENERHTN Investigators. Clinic Versus Ambulatory Blood Pressure in Resistant Hypertension: Impact of Antihypertensive Medication Nonadherence: A Post Hoc Analysis the DENERHTN Study. Hypertension. 2019 Nov;74(5):1096-1103. doi: 10.1161/HYPERTENSIONAHA.119.13520. Epub 2019 Sep 23.
citation: Courand PY, Pereira H, Del Giudice C, Gosse P, Monge M, Bobrie G, Delsart P, Mounier-Vehier C, Lantelme P, Denolle T, Dourmap C, Halimi JM, Girerd X, Rossignol P, Zannad F, Ormezzano O, Vaisse B, Herpin D, Ribstein J, Bouhanick B, Mourad JJ, Ferrari E, Chatellier G, Sapoval M, Azarine A, Azizi M; DENERHTN Investigators. Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial. J Am Heart Assoc. 2017 Oct 10;6(10):e007062. doi: 10.1161/JAHA.117.007062.
citation: Gosse P, Cremer A, Pereira H, Bobrie G, Chatellier G, Chamontin B, Courand PY, Delsart P, Denolle T, Dourmap C, Ferrari E, Girerd X, Michel Halimi J, Herpin D, Lantelme P, Monge M, Mounier-Vehier C, Mourad JJ, Ormezzano O, Ribstein J, Rossignol P, Sapoval M, Vaisse B, Zannad F, Azizi M. Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation: The DENERHTN Study (Renal Denervation for Hypertension). Hypertension. 2017 Mar;69(3):494-500. doi: 10.1161/HYPERTENSIONAHA.116.08448. Epub 2017 Jan 23.
citation: Azizi M, Pereira H, Hamdidouche I, Gosse P, Monge M, Bobrie G, Delsart P, Mounier-Vehier C, Courand PY, Lantelme P, Denolle T, Dourmap-Collas C, Girerd X, Michel Halimi J, Zannad F, Ormezzano O, Vaisse B, Herpin D, Ribstein J, Chamontin B, Mourad JJ, Ferrari E, Plouin PF, Jullien V, Sapoval M, Chatellier G; DENERHTN Investigators. Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial. Circulation. 2016 Sep 20;134(12):847-57. doi: 10.1161/CIRCULATIONAHA.116.022922. Epub 2016 Aug 30.
citation: Azizi M, Sapoval M, Gosse P, Monge M, Bobrie G, Delsart P, Midulla M, Mounier-Vehier C, Courand PY, Lantelme P, Denolle T, Dourmap-Collas C, Trillaud H, Pereira H, Plouin PF, Chatellier G; Renal Denervation for Hypertension (DENERHTN) investigators. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet. 2015 May 16;385(9981):1957-65. doi: 10.1016/S0140-6736(14)61942-5. Epub 2015 Jan 26.
citation: Persu A, Sapoval M, Azizi M, Monge M, Danse E, Hammer F, Renkin J. Renal artery stenosis following renal denervation: a matter of concern. J Hypertens. 2014 Oct;32(10):2101-5. doi: 10.1097/HJH.0000000000000323. No abstract available.