title: The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications.
abstract: Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal denervation efficacy. The 2 initial trials of the program focus on the effect of renal denervation using the Symplicity Spyral multielectrode renal denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal denervation or sham procedure. Both studies allow renal denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal denervation.
authors.affiliation: Piedmont Heart Institute, Atlanta, GA. Electronic address: david.kandzari@piedmont.org.
authors.forename: David E
authors.initials: DE
authors.lastname: Kandzari
authors.affiliation: Department of Cardiovascular Medicine, Jichi Medical University School of Medicine, Tochigi, Japan.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
authors.affiliation: Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Mahfoud
authors.affiliation: Department of Clinical Research, Medtronic, Santa Rosa, CA; Cardiovascular Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Sidney A
authors.initials: SA
authors.lastname: Cohen
authors.affiliation: Department of Clinical Research, Medtronic, Santa Rosa, CA.
authors.forename: Garrett
authors.initials: G
authors.lastname: Pilcher
authors.affiliation: Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Pocock
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Townsend
authors.affiliation: SUNY Downstate College of Medicine, Brooklyn, NY.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weber
authors.affiliation: Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017763:Autonomic Denervation / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000628:therapy*; D007668:Kidney / Q000294:innervation*; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents