Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials
Authors: Kirtane Ajay J. , Sharp Andrew S. P. , Mahfoud Felix , Fisher Naomi D. L. , Schmieder Roland E. , Daemen Joost , Lobo Melvin D. , Lurz Philipp , Basile Jan , Bloch Michael J. , Weber Michael A. , Saxena Manish , Wang Yale , Sanghvi Kintur , Jenkins J. Stephen , Devireddy Chandan , Rader Florian , Gosse Philippe , Sapoval Marc , Barman Neil C. , Claude Lisa , Augustin Dimitri , Thackeray Lisa , Mullin Christopher M. , Azizi Michel ,   RADIANCE Investigators and Collaborators, McClure Candace K. , Chertow Glenn , Chandra Venita , Dauerman Harold , Kahan Thomas , Ullery Steven , Beohar Nirat , Dogan Ozgen , Mokrzycki Michelle , Mullaney Scott , Redfors Bjorn , Vefali Huseng , Abbott J. Dawn , Loening Andreas , Zagoria Ron , Skeik Nedaa , Bae Richard , McMeans Amy , Goldman JoAnne , Peterson Rose , Jay Desmond , Schwartz Robert , Reilly John , Cash Micheal , Tutor Isabelle , Harrison Michael , Williams Shannon Williams , Jarvis Maria , Penning Angel , Lea Janice , Fiebach Amanda , Merlin Claudia , Wells Bryan , Dohad Suhail , Tran Anne , Bhatia Kirin , Kim Hyun-Min , Rashid Mohammad , Victor Ronald , Sobieszczyk Piotr , Halliday Ian , Munson Tay , Mauri Laura , Smith Alex , Aseltine Laura , Williams Jonathan , Lindsey Jason , Laster Steven , Bunte Mathew , Hart Anthony , King Dana , Hall Jamie , Costello Josh , Krathen Courtney , Lewis Luot , McElvarr Andrew , Willitts Ashley , Todoran Thomas , Powers Eric , Palmer Casey , Hodskins Emily , Paladugu Vijay , Tecklenburg Anna , Schindler John , Pacella John , Muldoon Matthew , Albright MaryJo , Nicholson Tracy , Flack John , Chami Youseff , Hafiz Abdul Moiz , Starkey Emily , Adams Kristal , Bernardo Nelson , Veis Judith , Hashim Hayder , Singh Suman , Whitman Donna , Stouffer Rick , Hinderliter Alan , Allen Meghan , Scholl Tatum , Pauley Eric , Wade Tyrone , Fong Pete , Laffer Chery , Gainer James , Robbins Mark , Crook Sherron , Hatchcock Ellen , Maddel Sarita , Cohen Debbie , Giri Jay , Kobayashi Taisei , Neubauer Robin , Naidu Suveeksha , Vo Thu , Radhakrishnan Jai , Batres Candido , Edwards Suzanne , Khuddus Matheen , Zentko Suzanne , Touchton Abby , Roberson Marti , O'Meara James , Barb Ilie , Foster Abby , Boyette Alice , Akinapelli Abhilash , English Lisa , Neumann Bridget , Roongsritong Chanwit , Nelson Priscilla , Mendelsohn Farrel , Brantley Hutton , Cawthon Thomas , DeRamus Susan , Wade Wesley , Fishman Robert , Tuohy Edward , LeBlanc Jessica , McCurry Tina , Krishnaswamy Amar , Laffin Luke , Bajzer Christopher , Boros Marilyn , Branche Monica , Abraham Josephine , Abraham Anu , Stijleman  Inge , Lavasani Iran , Neilson Hailey , Owan Theophilus , Hsi David , Martin Scott , Portnay Edward , Ducey Maryanne , Fiebach Maryann , Rose Suzanne , DelMasro Elizabeth , Garavito Carolina , Adams Todd , Teklinski Andrew , Leech Adam , Drilling Patrick , Tulik Lynda , Benzuly Keith , Paparello James , Fintel Dan , Ramirez Haydee , Kats Lauren , Huang Paul , Biswas Santanu , Risher Serena , Pratt Kristina , Ibebuogu Uzoma , Johnson Karen , Cushman William , Jones Lisa , Jackson Leigh , Landers David , Pasala Tilak , Salazer Thomas , Canino Peter , Arakelian Patricia , Yang Yi-Ming , Khaliq Asma , Weinberg Mitchell , Abetu Yihenew , Gulliver Alana , Garasic Joseph , Drachman Doug , Zusman Randy , Rosenfield Keneth , Do Danny , Chugh Atul , Bertolet Barry , Go Brian , Gallapudi Raghava , Cohn Joel , Rogers Kevin , Bangalore Sripal , Williams Stephan , Cabos Stanley , Rodriguez Alvarez Carolina , Calhoun David , McElderry Thomas , Maddox William , Oparil Suzanne , Kinder Sheila , Goldman Jessie , Ledley Gary , Katof Nancy , Aggarwal Sandeep , Potluri Sriivasa , Biedermann Scott , Ward Jacquelyn , White Megan , Zidar David , Shishehbor Mehdi , Effron Barry , Costa Marco , Semenec Terence , Huang Pei-Hsiu , Jose Powell , Jones Micheal , Mathur Anthony , Jain Ajay , Balawon Armida , Zongo Oliver , Topham Christine , Anderson Richard , Thompson Elizabeth , Spiro Nikki , Hodges Elizabeth , Holder Jaqueine , D'Souza Richard J. , Statton Sarah , Wilkes Lindsay , Joseph Anil , Ellam Timothy , Bagnall Alan , Jackson Ralph , Bridgett Victoria , Wilson Peter , Das Neelanjan , Doulton Timothy , Loader David , Hector Gemma , Levy Terry , Bent Clare , Kodoth Vivek , Horler Stephanie , Nix Sara , Beckett David , Lakeman Nicki , Kennard Sarah , Patel Amit , Robinson Nicholas , Al-Janabi Faris , Sayer Jeremy , Iyer Sudha Ganesh , Redman Emily , Ramirez Jonaifah , Sevillano Annaliza , Ocampo Madelaine , Ali Edroos Sadat , Padmanabhan Sandosh , Gerber Robert , Faris Mohamad , Marshall Andrew John , Sinclair Janet , Pepper Hayley , Elorz Cristina , David Justin , Chapman Neil , Burak Paula , Carvelli Paula , Shun Shin Matthew , Howard James , Jadhav Sachin , Quinn Jane , Sharif Faisal , Alhmoudi Aishah , Lunardi Mattia , Coen Eileen , Glynn Nicola , Böhm Michael , Lauder Lucas , Kulenthiran Saarraaken , Koch Christina , Wachter Angelika , Ewen Sebastian , Lucic Jelena , Schmid Axel , Kannenkeril Dennis , Ott Christian , Uder Michael , Heinritz Ulrike , Fröhlich-Endres Kerstin , Rommel Karl -Philipp , Fengler Karl  , Höllriegel Robert , Petzold Martin , Büttner Margit , Trautmann Kai , Weil Joachim , Agdirlioglu Tolga , Köllner Tanja , Stephan Jeannine , Hafer Lukas , Dagkonakis Nikolaos , Hamann Frank , Reimer Peter , Hausberg Martin , Ettl Ute , Petzsche Ulrike , Hinrichs Ralf , Di Ponio-Voit Isabella , Lutz Matthias , Rump Lars Christian , Stegbauer Johannes , Schimmöller Lars , Potthoff Sebastian , Schmid Claudia , Roeder Sylvia , Kröpil Patric , Genth-Zotz Sabine , Kämpfner Denise , Grawe Armin , Höhne Johannes , Kaesberger Bärbel , von zur Mühlen Constantin , Wolf Dennis , Welzel Markus , Heinrichs Gudrun , Trabitzsch Barbara , Cremer Antoine , Papadopoulos Panteleimon , Gaudissard Julie , Maire Florent , Trillaud Hervé , Livrozet Marine , Regrag Asma , Paquet Valerie , Cornu Erika , Fouassier David , Lorthioir Aurélien , Delsart Pascal , Hennicaux Justin , Longere Benjamin , Bailly-Sommeville Coralie , Bertrand Fabien , Ledieu Guillaume , Pontana François , Pathak Atul , Honton Benjamin , Cottin Marianne , Petit Frédéric , Lantelme Pierr , Berge Constance , Courand Pierre-Yves , Langevin Fatou , Lafeber Melvin , Zeijen Victor , Ruiter Arno , Huijskens Elisabeth , Feyz Lida , van Ramshorst Jan , Blankestijn Peter , Voskuil Michiel , Rittersma Zwaantina , Dolmans Helma , Kroon A.A. , van Zwam W.H. , Vranken Jeannique , de Haan Claudia , Xaplanteris Panagiotis , Briki Rachid , de Hemptinne Quentin , Pascal Severine , Renard Katty , Lefebvre Pascal , Ferdinande Bert , Persu Alexandre , Renkin Jean , Maes Frédéric , Beauloye Christophe , Lengelé Jean-Philippe , Huyberechts Dominique , Bouvier Anne , Iglesias Juan F. , Ehret Georg , Gallego Laetitia , Dobretz Kevin , Bottone Sylviane , Witkowski Adam , Januszewicz Andrzej , Kądziela Jacek Kądziela , Prejbisj Aleksander , Hering Dagmara , Ciecwierz Dariusz , Jaguszewski Milosz J. , Owczuk Radoslaw 
Published: February 2023

Importance

Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important.

Objective

To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy.

Data Sources

A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials.

Study Selection

Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up.

Data Extraction and Synthesis

Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials.

Main Outcomes and Measures

The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups.

Results

A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, −5.9; 95% CI, −8.1 to −3.8 mm Hg; P &amp;lt; .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: −10.4 mm Hg vs −3.4 mm Hg; mean difference, −6.4 mm Hg; 95% CI, −9.1 to –3.6 mm Hg; home SBP: −8.4 mm Hg vs −1.4 mm Hg; mean difference, −6.8 mm Hg; 95% CI, −8.7 to −4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups.

Conclusions and Relevance

Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups.

Trial Registration

ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260