Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial

Michel Azizi; Kintur Sanghvi; Manish Saxena; Philippe Gosse; John P Reilly; Terry Levy; Lars C Rump; Alexandre Persu; Jan Basile; Michael J Bloch; Joost Daemen; Melvin D Lobo; Felix Mahfoud; Roland E Schmieder; Andrew S P Sharp; Michael A Weber; Marc Sapoval; Pete Fong; Atul Pathak; Pierre Lantelme; David Hsi; Sripal Bangalore; Adam Witkowski; Joachim Weil; Benjamin Kably; Neil C Barman; Helen Reeve-Stoffer; Leslie Coleman; Candace K McClure; Ajay J Kirtane

doi:10.1016/S0140-6736(21)00788-1

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial

Michel Azizi, Kintur Sanghvi, Manish Saxena, Philippe Gosse, John P Reilly, Terry Levy, Lars C Rump, Alexandre Persu, Jan Basile, Michael J Bloch, Joost Daemen, Melvin D Lobo, Felix Mahfoud, Roland E Schmieder, Andrew S P Sharp, Michael A Weber, Marc Sapoval, Pete Fong, Atul Pathak, Pierre LantelmeDavid Hsi, Sripal Bangalore, Adam Witkowski, Joachim Weil, Benjamin Kably, Neil C Barman, Helen Reeve-Stoffer, Leslie Coleman, Candace K McClure, Ajay J Kirtane,

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications.

METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426.

FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups.

INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension.

FUNDING: ReCor Medical.

Original language	English
Pages (from-to)	2476-2486
Number of pages	11
Journal	Lancet (London, England)
Volume	397
Issue number	10293
DOIs	https://doi.org/10.1016/S0140-6736(21)00788-1
Publication status	Published - 26 Jun 2021

Keywords

Angiotensin Receptor Antagonists/therapeutic use
Blood Pressure Monitoring, Ambulatory
Calcium Channel Blockers/therapeutic use
Denervation/methods
Drug Resistance
Endovascular Procedures/methods
Female
Humans
Hypertension/therapy
Kidney/blood supply
Male
Middle Aged
Renal Artery/innervation
Single-Blind Method
Sodium Chloride Symporter Inhibitors/therapeutic use
Ultrasonic Surgical Procedures/methods

Access to Document

10.1016/S0140-6736(21)00788-1

Cite this

Azizi, M., Sanghvi, K., Saxena, M., Gosse, P., Reilly, J. P., Levy, T., Rump, L. C., Persu, A., Basile, J., Bloch, M. J., Daemen, J., Lobo, M. D., Mahfoud, F., Schmieder, R. E., Sharp, A. S. P., Weber, M. A., Sapoval, M., Fong, P., Pathak, A. (2021). Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. Lancet (London, England), 397(10293), 2476-2486. https://doi.org/10.1016/S0140-6736(21)00788-1

@article{258c2dcf1e2e4083965331dffa676d91,

title = "Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial",

abstract = "BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications.METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426.FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups.INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension.FUNDING: ReCor Medical.",

keywords = "Angiotensin Receptor Antagonists/therapeutic use, Blood Pressure Monitoring, Ambulatory, Calcium Channel Blockers/therapeutic use, Denervation/methods, Drug Resistance, Endovascular Procedures/methods, Female, Humans, Hypertension/therapy, Kidney/blood supply, Male, Middle Aged, Renal Artery/innervation, Single-Blind Method, Sodium Chloride Symporter Inhibitors/therapeutic use, Ultrasonic Surgical Procedures/methods",

author = "Michel Azizi and Kintur Sanghvi and Manish Saxena and Philippe Gosse and Reilly, {John P} and Terry Levy and Rump, {Lars C} and Alexandre Persu and Jan Basile and Bloch, {Michael J} and Joost Daemen and Lobo, {Melvin D} and Felix Mahfoud and Schmieder, {Roland E} and Sharp, {Andrew S P} and Weber, {Michael A} and Marc Sapoval and Pete Fong and Atul Pathak and Pierre Lantelme and David Hsi and Sripal Bangalore and Adam Witkowski and Joachim Weil and Benjamin Kably and Barman, {Neil C} and Helen Reeve-Stoffer and Leslie Coleman and McClure, {Candace K} and Kirtane, {Ajay J} and Michiel Voskuil",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2021",

month = jun,

day = "26",

doi = "10.1016/S0140-6736(21)00788-1",

language = "English",

volume = "397",

pages = "2476--2486",

journal = "Lancet (London, England)",

issn = "0140-6736",

publisher = "Elsevier",

number = "10293",

}

Azizi, M, Sanghvi, K, Saxena, M, Gosse, P, Reilly, JP, Levy, T, Rump, LC, Persu, A, Basile, J, Bloch, MJ, Daemen, J, Lobo, MD, Mahfoud, F, Schmieder, RE, Sharp, ASP, Weber, MA, Sapoval, M, Fong, P, Pathak, A, Lantelme, P, Hsi, D, Bangalore, S, Witkowski, A, Weil, J, Kably, B, Barman, NC, Reeve-Stoffer, H, Coleman, L, McClure, CK, Kirtane, AJ 2021, 'Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial', Lancet (London, England), vol. 397, no. 10293, pp. 2476-2486. https://doi.org/10.1016/S0140-6736(21)00788-1

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. / Azizi, Michel; Sanghvi, Kintur; Saxena, Manish et al.
In: Lancet (London, England), Vol. 397, No. 10293, 26.06.2021, p. 2476-2486.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO)

T2 - a randomised, multicentre, single-blind, sham-controlled trial

AU - Azizi, Michel

AU - Sanghvi, Kintur

AU - Saxena, Manish

AU - Gosse, Philippe

AU - Reilly, John P

AU - Levy, Terry

AU - Rump, Lars C

AU - Persu, Alexandre

AU - Basile, Jan

AU - Bloch, Michael J

AU - Daemen, Joost

AU - Lobo, Melvin D

AU - Mahfoud, Felix

AU - Schmieder, Roland E

AU - Sharp, Andrew S P

AU - Weber, Michael A

AU - Sapoval, Marc

AU - Fong, Pete

AU - Pathak, Atul

AU - Lantelme, Pierre

AU - Hsi, David

AU - Bangalore, Sripal

AU - Witkowski, Adam

AU - Weil, Joachim

AU - Kably, Benjamin

AU - Barman, Neil C

AU - Reeve-Stoffer, Helen

AU - Coleman, Leslie

AU - McClure, Candace K

AU - Kirtane, Ajay J

AU - Voskuil, Michiel

PY - 2021/6/26

Y1 - 2021/6/26

N2 - BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications.METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426.FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups.INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension.FUNDING: ReCor Medical.

AB - BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications.METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426.FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups.INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension.FUNDING: ReCor Medical.

KW - Angiotensin Receptor Antagonists/therapeutic use

KW - Blood Pressure Monitoring, Ambulatory

KW - Calcium Channel Blockers/therapeutic use

KW - Denervation/methods

KW - Drug Resistance

KW - Endovascular Procedures/methods

KW - Female

KW - Humans

KW - Hypertension/therapy

KW - Kidney/blood supply

KW - Male

KW - Middle Aged

KW - Renal Artery/innervation

KW - Single-Blind Method

KW - Sodium Chloride Symporter Inhibitors/therapeutic use

KW - Ultrasonic Surgical Procedures/methods

U2 - 10.1016/S0140-6736(21)00788-1

DO - 10.1016/S0140-6736(21)00788-1

M3 - Article

C2 - 34010611

SN - 0140-6736

VL - 397

SP - 2476

EP - 2486

JO - Lancet (London, England)

JF - Lancet (London, England)

IS - 10293

ER -

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial

Abstract

Keywords

Access to Document

Fingerprint

Cite this