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Phase II randomized sham-controlled study of renal denervation for individuals with uncontrolled hypertension – WAVE IV

Schmieder, Roland, E.a; Ott, Christiana; Toennes, Stefan, W.b; Bramlage, Peterc; Gertner, Michaeld; Dawood, Omare; Baumgart, Peterf; O’Brien, Benjaming,h; Dasgupta, Indranili; Nickenig, Georgj; Ormiston, Johnk; Saxena, Manishg; Sharp, Andrew, S.P.l; Sievert, Horstm; Spinar, Jindrichn,o; Starek, Zdenekp; Weil, Joachimq; Wenzel, Ulrichr; Witkowski, Adams; Lobo, Melvin, D.g

doi: 10.1097/HJH.0000000000001584
ORIGINAL PAPERS: Therapeutic aspects
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Objectives: The aim of this double-blind, randomized, sham-controlled study was to verify the blood pressure (BP)-lowering efficacy of externally delivered focused ultrasound for renal denervation (RDN).

Background: Nonrandomized, first proof-of-concept study and experimental evidence suggested that noninvasive techniques of RDN emerged as an alternative approach of RDN to invasive technologies.

Methods: WAVE IV, an international, randomized (1 : 1) sham-controlled, double-blind prospective clinical study, was prematurely stopped. Patients were enrolled if office BP was at least 160 mmHg and 24-h ambulatory BP was at least 135 mmHg, while taking three or more antihypertensive medications. The treatment consisted of bilateral RDN using therapeutic levels of ultrasound energy and the sham consisted of bilateral application of diagnostic levels of ultrasound energy.

Results: In the 81 treated patients neither changes in office BP at 12 and 24 weeks, nor changes in 24-h ambulatory BP at 24-week follow-up visit differed between the two groups significantly. Of note, no safety signal was observed. Adherence analysis disclosed full adherence in 77% at baseline and 82% at 6 months’ follow-up visit. Post hoc analysis revealed that stricter criteria for stabilization of BP at baseline were associated with a numerically greater change in 24-h ambulatory BP in the RDN group than in the sham group.

Conclusion: Our data did not prove that antihypertensive efficacy of the externally delivered focused ultrasound for RDN was greater than the sham effect. Stabilization of BP at baseline was identified as an important determinant of BP changes.

aDepartment of Nephrology and Hypertension, University Hospital of the Friedrich-Alexander University Erlangen-Nürnberg, Erlangen

bInstitute of Legal Medicine, Forensic Toxicology Department, Goethe University, Frankfurt/Main

cInstitute for Preventive Medicine, Mahlow, Germany

dKona Medical, Department of Surgery, Stanford School of Medicine, Stanford, California

eKona Medical, Bellevue, Washington, USA

fMedizinische Klinik I, Clemenshospital GmbH, Münster, Germany

gNIHR Barts Cardiovascular Biomedical Research Unit, William Harvey Research Institute

hSt Bartholomew's Hospital, London

iRenal Unit, Heart of England NHS Foundation Trust, Birmingham, UK

jKardiologie, Angiologie und Pneumologie, Universitätsklinikum Bonn, Bonn, Germany

kMercy Angiography, Auckland, New Zealand

lRoyal Exeter and Devon Hospital, Exeter, UK

mCardioVascular Center, Sankt Katharinen Hospital, Frankfurt, Germany

nCardiology Department, University Hospital Brno

oMedical Faculty, Masaryk University Brno

pI. International Clinical Research Center, St. Anne's University Hospital, 1st Department of Internal Medicine/Cardioangiology, Brno, Czech Republic

qMedizinische Klinik II, Kardiologie und Angiologie, Sana Kliniken Lübeck, Lübeck

rUniversitätsklinikum Hamburg-Eppendorf, III. Medizinische Klinik und Poliklinik Hamburg, Germany

sDepartment of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland

Correspondence to Roland E. Schmieder, University Hospital of the Friedrich-Alexander-University Erlangen-Nürnberg, Nephrology and Hypertension, Ulmenweg 18, Erlangen 91054, Germany. Tel: +9131 85 36245; fax: +9131 85 36215; e-mail: Roland.Schmieder@uk-erlangen.de, roland.schmieder@fau.de

Abbreviations: ABPM, ambulatory BP monitoring; BP, blood pressure; eGFR, estimated glomerular filtration rate; ITT, intention to treat; MI, myocardial infarction; RDN, therapeutic renal denervation; SEM, standard error of the mean; SNS, sympathetic nervous system; TRH, treatment-resistant hypertension

Received 12 May, 2017

Revised 15 August, 2017

Accepted 4 September, 2017

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