title: Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 Trial.
abstract: Hypertension represents a significant global public health concern, contributing to vascular and renal morbidity, cardiovascular mortality, and economic burden. The opportunity to influence clinical outcomes through hypertension management is therefore paramount. Despite adherence to multiple available medical therapies, a significant proportion of patients have persistent blood pressure elevation, a condition termed resistant hypertension. Recent recognition of the importance of the renal sympathetic and somatic nerves in modulating blood pressure and the development of a novel procedure that selectively removes these contributors to resistant hypertension represents an opportunity to provide clinically meaningful benefit across wide and varied patient populations. Early clinical evaluation with catheter-based, selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity, increased renal plasma flow, and has demonstrated clinically significant, sustained reductions in blood pressure. The SYMPLICITY HTN-3 Trial is a pivotal study designed as a prospective, randomized, masked procedure, single-blind trial evaluating the safety and effectiveness of catheter-based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes (at least one of which is a diuretic) at maximal tolerable doses. The primary effectiveness endpoint is measured as the change in office-based systolic blood pressure from baseline to 6 months. This manuscript describes the design and methodology of a regulatory trial of selective renal denervation for the treatment of hypertension among patients who have failed pharmacologic therapy.
authors.affiliation: Piedmont Heart Institute, Atlanta, GA, USA. david.kandzari@piedmont.org
authors.forename: David E
authors.initials: DE
authors.lastname: Kandzari
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sobotka
authors.forename: William W
authors.initials: WW
authors.lastname: O'Neill
authors.forename: Murray
authors.initials: M
authors.lastname: Esler
authors.forename: John M
authors.initials: JM
authors.lastname: Flack
authors.forename: Barry T
authors.initials: BT
authors.lastname: Katzen
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.forename: Manuela
authors.initials: M
authors.lastname: Negoita
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: Krishna
authors.initials: K
authors.lastname: Rocha-Singh
authors.forename: Craig
authors.initials: C
authors.lastname: Straley
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.forename: George
authors.initials: G
authors.lastname: Bakris
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D057785:Catheters; D006801:Humans; D006973:Hypertension / Q000601:surgery*; D007668:Kidney / Q000294:innervation / Q000601:surgery*; D008875:Middle Aged; D012077:Renal Artery / Q000601:surgery*; D012107:Research Design; D016037:Single-Blind Method; D013562:Sympathectomy / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult