Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program
Authors: Azizi Michel , Sharp Andrew S.P. , Fisher Naomi D.L. , Weber Michael A. , Lobo Melvin D. , Daemen Joost , Lurz Philipp , Mahfoud Felix , Schmieder Roland E. , Basile Jan , Bloch Michael J. , Saxena Manish , Wang Yale , Sanghvi Kintur , Jenkins J. Stephen , Devireddy Chandan , Rader Florian , Gosse Philippe , Claude Lisa , Augustin Dimitri A. , McClure Candace K. , Kirtane Ajay J. , Wang Yale , Skeik Nedaa , Bae Richard , McMeans Amy , Goldman JoAnne , Peterson Rose , Stephen Jenkins James , Tutor Isabelle , Harrison Michael , Penning Angel , Devireddy Chandan , Lea Janice , Fiebach Amanda , Merlin Claudia , Rader Florian , Dohad Suhail , Tran Anne , Bhatia Kirin , Fisher Naomi D.L. , Sobieszczyk Piotr , Halliday Ian , Munson Tay , Lindsey Jason , Laster Steven , Bunte Mathew , Hart Anthony , King Dana , Hall Jamie , Sanghvi Kintur , Krathen Courtney , Lewis Luot , Willitts Ashley , Todoran Thomas , Basile Jan , Awkar Anthony , Palmer Casey , 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 , Fong Pete , Gainer James , Crook Sherron , Hatchcock Ellen , Cohen Debbie , Giri Jay , Kobayashi Taisei , Neubauer Robin , Naidu Suveeksha , Kirtane Ajay J. , Radhakrishnan Jai , Batres Candido , Edwards Suzanne , Khuddus Matheen , Zentko Suzanne , Touchton Abby , Roberson Marti , Bloch Michael J. , Akinapelli Abhilash , English Lisa , Neumann Bridget , 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 , Hsi David , Martin Scott , Portnay Edward , Fiebach Maryann , 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 , Reilly J.P. , Garasic Joseph , Chugh Atul , Bertolet Barry , Go Brian , Gallapudi Raghava , Cohn Joel , Rogers Kevin , Saxena Manish , Mathur Anthony , Jain Ajay , Balawon Armida , Zongo Oliver , Topham Christine , Sharp Andrew , Anderson Richard , Thompson Elizabeth , Spiro Nikki , Hodges Elizabeth , Holder Jaqueline , 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 , Robinson Nicholas , Al-Janabi Firas , Sayer Jeremy , Ganesh Iyer Sudha , Redman Emily , Ramirez Jonaifah , Padmanabhan Sandosh , Sharif Faisal , Alhmoudi Aishah , Lunardi Mattia , Coen Eileen , Glynn Nicola , Mahfoud Felix , Lauder Lucas , Kulenthiran Saarraaken , Koch Christina , Wachter Angelika , Schmieder Roland , Schmid Axel , Kannenkeril Dennis , Heinritz Ulrike , Endres-Frohlich Kerstin , Lurz Philipp , Rommel Karl , Fengler  , Petzold Martin , Büttner Margit , Weil Joachim , Agdirlioglu Tolga , Köllner Tanja , Stephan Jeannine , Dagkonakis Nikolaos , Hamann Frank , Ettl Ute , Petzsche Ulrike , Reimer Peter , Hausberg Martin , Hinrichs Ralf , Di Ponio-Voit Isabella , Lutz Matthias , Gosse Philippe , Cremer Antoine , Papadopoulos Panteleimon , Gaudissard Julie , Maire Florent , Azizi Michel , Sapoval Marc , Livrozet Marine , Regrag Asma , Paquet Valerie , Delsart Pascal , Hennicaux Justin , Sommeville Coralie , Bertrand Fabien , Daemen Joost , Lafeber Melvin , Zeijen Victor , Ruiter Amo , Huijskens Elisabeth , van Ramshorst Jan , Xaplanteris Panagiotis , Briki Rachid , de Hemptinne Quentin , Pascal Severine , Renard Katty , Ferdinande Bert , Iglesias Juan F. , Ehert Georg , Gallego Laetitia , Dobretz Kevin , Bottone Sylviane , Sanghvi Kintur , Costello Josh , Krathan Courtney , Lewis Luot , McElvarr Andrew , Reilly John , Jenkins Stephen , Cash Michael , Williams Shannon , Jarvis Maria , Fong Pete , Laffer Cheryl , Gainer James , Robbins Mark , Crook Sherron , Maddel Sarita , Hsi David , Martin Scott , Portnay Edward , Ducey Maryanne , Rose Suzanne , DelMastro Elizabeth , Bangalore Sripal , Williams Stephen , Cabos Stanley , Rodriguez Alvarez Carolina , Todoran Thomas , Basile Jan , Powers Eric , Hodskins Emily , Paladugu Vijay , Tecklenburg Anna , Devireddy Chandan , Lea Janice , Wells Bryan , Fiebach Amanda , Merlin Claudia , Rader Florian , Dohad Suhail , Kim Hyun-Min , Rashid Mohammad , Abraham Josephine , Owan Theophilus , Abraham Anu , Lavasani Iran , Neilson Hailey , Calhoun David , McElderry Thomas , Maddox William , Oparil Suzanne , Kinder Sheila , Kirtane Ajay J. , Radhakrishnan Jai , Batres Candido , Edwards Suzanne , Garasic Joseph , Drachman Doug , Zusman Randy , Rosenfield Kenneth , Do Danny , Khuddus Matheen , Zentko Suzanne , O’Meara James , Barb Ilie , Foster Abby , Boyette Alice , Wang Yale , Jay Desmond , Skeik Nedaa , Schwartz Robert , Peterson Rose , Goldman Jo Anne , Goldman Jessie , Ledley Gary , Katof Nancy , Potluri Srinivasa , Biedermann Scott , Ward Jacquelyn , White Megan , Fisher Naomi D.L. , Mauri Laura , Sobieszczky Piotr , Smith Alex , Aseltine Laura , Stouffer Rick , Hinderliter Alan , Pauley Eric , Wade Tyrone , Zidar David , Shishehbor Mehdi , Effron Barry , Costa Marco , Semenec Terence , Bloch Michael J. , Roongsritong Chanwit , Nelson Priscilla , Neumann Bridget , Cohen Debbie , Giri Jay , Neubauer Robin , Vo Thu , Chugh Atul R. , Huang Pei-Hsiu , Jose Powell , Flack John , Fishman Robert , Jones Michael , Adams Todd , Bajzer Christopher , Saxena Manish , Lobo Melvin D. , Mathur Anthony , Jain Ajay , Balawon Armida , Zongo Olivier , Levy Terry , Bent Clare , Beckett David , Lakeman Nicki , Kennard Sarah , Sharp Andrew , D’Souza Richard J. , Statton Sarah , Wilkes Lindsay , Anning Christine , Sayer Jeremy , Ganesh Iyer Sudha , Robinson Nicholas , Sevillano Annaliza , Ocampo Madelaine , Gerber Robert , Faris Mohamad , John Marshall Andrew , Sinclair Janet , Pepper Hayley , Davies Justin , Chapman Neil , Burak Paula , Carvelli Paula , Jadhav Sachin , Quinn Jane , Christian Rump Lars , Stegbauer Johannes , Schimmöller Lars , Potthoff Sebastian , Schmid Claudia , Roeder Sylvia , Weil Joachim , Hafer Lukas , Agdirlioglu Tolga , Köllner Tanja , Mahfoud Felix , Böhm Michael , Ewen Sebastian , Kulenthiran Saarraaken , Wachter Angelika , Koch Christina , Lurz Philipp , Fengler Karl , Rommel Karl-Philipp , Trautmann Kai , Petzold Martin , Schmieder Roland E. , Ott Christian , Schmid Axel , Uder Michael , Heinritz Ulrike , Fröhlich-Endres Kerstin , Genth-Zotz Sabine , Kämpfner Denise , Grawe Armin , Höhne Johannes , Kaesberger Bärbel , von zur Mühlen Constantin , Wolf Dennis , Welzel Markus , Gosse Philippe , Cremer Antoine , Trillaud Hervé , Papadopoulos Panteleimon , Maire Florent , Gaudissard Julie , Azizi Michel , Sapoval Marc , Cornu Erika , Fouassier David , Livrozet Marine , Lorthioir Aurélien , Paquet Valérie , Pathak Atul , Honton Benjamin , Cottin Marianne , Petit Frédéric , Lantelme Pierre , Berge Constance , Courand Pierre-Yves , Langevin Fatou , Delsart Pascal , Longere Benjamin , Ledieu Guillaume , Pontana François , Sommeville Coralie , Bertrand Fabien , Daemen Joost , Feyz Lida , Zeijen Victor , Ruiter Arno , Huyskens Elisabeth , Blankestijn Peter , Voskuil Michiel , Rittersma Zwaantina , Dolmans Helma , Kroon A.A. , van Zwam W.H. , Vranken Jeannique , de Haan Claudia , Persu Alexandre , Renkin Jean , Maes Frédéric , Beauloye Christophe , Lengelé Jean-Philippe , Huyberechts Dominique , Bouvier Anne , Witkowski Adam , Januszewicz Andrzej , Kądziela Jacek , Prejbisj Aleksander , Hering Dagmara , Ciecwierz Dariusz , Jaguszewski Milosz J. , Owczuk Radoslaw , Ciecwierz Dariusz , Jaguszewski Milosz J. , Wang Yale , Jay Desmond , Skeik Nedaa , Schwartz Robert , Rader Florian , Dohad Suhail , Victor Ronald , Sanghvi Kintur , Costello Josh , Walsh Courtney , Abraham Josephine , Owan Theophilus , Abraham Anu , Fisher Naomi D.L. , Mauri Laura , Sobieszczky Piotr , Williams Jonathan , Bloch Michael J. , Roongsritong Chanwit , Todoran Thomas , Basile Jan , Powers Eric , Hodskins Emily , Fong Pete , Laffer Cheryl , Gainer James , Robbins Mark , Reilly John , Cash Michael , Goldman Jessie , Aggarwal Sandeep , Ledley Gary , Hsi David , Martin Scott , Portnay Edward , Calhoun David , McElderry Thomas , Maddox William , Oparil Suzanne , Huang Pei-Hsiu , Jose Powell , Khuddus Matheen , Zentko Suzanne , O’Meara James , Barb Ilie , Garasic Joseph , Drachman Doug , Zusman Randy , Rosenfield Kenneth , Devireddy Chandan , Lea Janice , Wells Bryan , Stouffer Rick , Hinderliter Alan , Pauley Eric , Potluri Srinivasa , Biedermann Scott , Bangalore Sripal , Williams Stephen , Zidar David , Shishehbor Mehdi , Effron Barry , Costa Marco , Kirtane Ajay J. , Radhakrishnan Jai , Lobo Melvin D. , Mathur Anthony , Jain Ajay , Sayer Jeremy , Ganesh Iyer Sudha , Robinson Nicholas , Ali Edroos Sadat , Levy Terry , Patel Amit , Beckett David , Bent Clare , Davies Justin , Chapman Neil , Shun Shin Matthew , Howard James , Sharp Andrew S.P. , Joseph Anil , D’Souza Richard , Gerber Robert , Faris Mohamad , John Marshall Andrew , Elorz Cristina , Lurz Philipp , Höllriegel Robert , Fengler Karl , Rommel Karl-Philipp , Mahfoud Felix , Böhm Michael , Ewen Sebastian , Lucic Jelena , Schmieder Roland E. , Ott Christian , Schmid Axel , Uder Michael , Rump Christian , Stegbauer Johannes , Kröpil Patric , Azizi Michel , Sapoval Marc , Cornu Erika , Fouassier David , Gosse Philippe , Cremer Antoine , Trillaud Hervé , Papadopoulos Panteleimon , Pathak Atul , Honton Benjamin , Lantelme Pierre , Berge Constance , Courand Pierre-Yves , Daemen Joost , Feyz Lida , Blankestijn Peter , Voskuil Michiel , Rittersma Zwaantina , Kroon A.A. , van Zwam W.H. , Persu Alexandre , Renkin Jean 
Published: October 2023

BACKGROUND:
The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials.

METHODS:
Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used.

RESULTS:

Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (
P
=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (
P
=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was −3.0 mm Hg (95% CI, −5.7, −0.2;
P
=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were −5.4 mm Hg (−6.8, −4.0;
P
<0.001) and −5.2 mm Hg (−7.1, −3.3;
P
<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups.

CONCLUSIONS:
This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT02649426 and NCT03614260.