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. 2023 May 1;8(5):464-473.
doi: 10.1001/jamacardio.2023.0338.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials

Ajay J Kirtane  1   2 , Andrew S P Sharp  3 , Felix Mahfoud  4   5 , Naomi D L Fisher  6 , Roland E Schmieder  7 , Joost Daemen  8 , Melvin D Lobo  9 , Philipp Lurz  10 , Jan Basile  11 , Michael J Bloch  12 , Michael A Weber  13 , Manish Saxena  9 , Yale Wang  14 , Kintur Sanghvi  15 , J Stephen Jenkins  16 , Chandan Devireddy  17 , Florian Rader  18 , Philippe Gosse  19 , Marc Sapoval  20   21   22 , Neil C Barman  23 , Lisa Claude  23 , Dimitri Augustin  23 , Lisa Thackeray  24 , Christopher M Mullin  24 , Michel Azizi  20   21   22 ; RADIANCE Investigators and Collaborators
Collaborators, Affiliations

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials

Ajay J Kirtane et al. JAMA Cardiol. .

Erratum in

  • Error in Supplement.
    [No authors listed] [No authors listed] JAMA Cardiol. 2023 Aug 1;8(8):797. doi: 10.1001/jamacardio.2023.1717. JAMA Cardiol. 2023. PMID: 37314758 Free PMC article. No abstract available.

Abstract

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 < .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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kirtane reported receiving grants from ReCor Medical, Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, Amgen, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, Shockwave Medical, and Merck; consulting fees from IMDS; and travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron during the conduct of the study. Dr Sharp reported receiving consultant fees from ReCor Medical, Medtronic, Philips, Boston Scientific, and Penumbra. Dr Mahfoud reported receiving grants from Medtronic, ReCor, Ablative Solutions; support from Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft and Deutsche Herzstiftung; and speaker honoraria from Medtronic, ReCor, Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Merck, Servier, and Terumo outside the submitted work. Dr Fisher reported receiving grant support and personal fees from ReCor Medical and personal fees from Medtronic outside the submitted work. Dr Schmieder reported receiving grant support and personal fees from ReCor Medical, Medtronic, and Ablative Solutions. Dr Daemen reported receiving institutional grant/research support from AstraZeneca, Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Microport, Pie Medical, and ReCor Medical; and consultancy and speaker fees from Abbott Vascular, Abiomed, ACIST Medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, ReCor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care, and Medtronic. Dr Lobo reported receiving personal fees from Ablative Solutions, Medtronic, ReCor Medical, and Vascular Dynamics and grant support from Medtronic during the conduct of the study. Dr Lurz reported receiving grants from ReCor Medical, Edwards Lifesciences and grant and personal fees from Abbott Medical outside the submitted work. Dr Basile reported receiving grants and consultant fees ReCor Medical and grants from Ablative Solutions during the conduct of the study. Dr Bloch reported receiving personal fees from ReCor Medical and Medtronic outside the submitted work. Dr Weber reported receiving personal fees from Medtronic, ReCor Medical, and Ablative Solutions outside the submitted work. Dr Saxena reported receiving grants from ReCor Medical, Ablative Solutions, Applied Therapeutics, Vascular Dynamics, and MSD and personal fees from ReCor Medical, Esperion, Daiichi Sankyo, Vifor Pharma, and Novartis outside the submitted work. Dr Sanghvi reported receiving grant support and consultant fees from ReCor Medical and Medtronic and has received grant support from CSI. Dr Jenkins reported receiving grants from Medtronic, Abbott, Abiomed and ReCor Medical and speaker honoraria from Abbott, ReCor Medical, and Medtronics. Dr Devireddy reported receiving personal fees from ReCor Medical, Medtronic, Edwards Lifesciences, and Shockwave Medical. Dr Rader has received personal fees from ReCor Medical, Medtronic, and Bristol Myers Squibb. Dr Gosse reported receiving research grants from ReCor Medical and Ablative Solutions. Dr Sapoval reported receiving personal fees from ReCor Medical and Medtronic and grants from Recor research grant during the conduct of the study, grants from Merit, and consulting fees from Boston Scientific outside the submitted work. Dr Barman, Ms Claude, and Dr Augustin reported being employees of ReCor Medical, and Dr Barman reported having a patent for multiple renal denervation patents issued during the conduct of the study. Ms Thackeray and Mr Mullin reported being employees of NAMSA, a contractor for ReCor Medical, and receiving consulting fees from ReCor Medical outside the submitted work. Dr Azizi reported receiving research grants from the European Horizon 2020 program and ReCor Medical, grant and nonfinancial support from ReCor Medical and Idorsia, and personal fees from Alnylam Pharmaceutical, Poxel Pharma, Medtronic, and Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Design of the 3 Studies Included in the Pooled Analysis
The studies included in the pooled analysis are 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. ABP indicates ambulatory blood pressure; BP, blood pressure; CTA, computed tomography angiography; HTN, hypertension; meds, medications; MRA, magnetic resonance angiography; uRDN, ultrasound-based renal denervation.
Figure 2.
Figure 2.. Pooled Results for Systolic Blood Pressure (SBP) Readings and SBP Curves Over a 24-Hour Period
A, Patient-level pooled results for SBP readings including daytime ambulatory (primary end point), 24-hour ambulatory, home, and office. Results include available data for each group (daytime ambulatory: ultrasound-based renal denervation [uRDN], 281; sham, 211; home: uRDN, 271; sham, 205; office: uRDN, 275; sham, 209). Between-group comparisons include multiple imputation for missing data. B, Ambulatory systolic BP curves over the 24-hour period at baseline and 2 months for uRDN and sham groups. Curves include available data (uRDN, 280; sham, 209) and impute for patients meeting escape criteria.
Figure 3.
Figure 3.. Between-Group Differences in 2-Month Daytime Ambulatory Systolic Blood Pressure (ASBP) Change for Prespecified Subgroups
AHR, indicates ambulatory heart rate; APP, ambulatory pulse pressure; BMI, body mass index; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; uRDN, ultrasound-based renal denervation. aCalculated as weight in kilograms divided by height in meters squared.
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