研究组招募年龄在18-75岁之间，尽管服用了三种及以上的降压药（包括利尿剂），但办公室血压仍至少为140/90 mmHg的患者。将这些患者的用药方案改为钙通道阻滞剂、血管紧张素受体阻滞剂和噻嗪类利尿剂的每日一次固定剂量单片组合。经过4周的标准化治疗后，白天动态血压至少为135/85 mmHg的患者被1：1随机分配（按中心分层）接受超声肾去神经术或假手术。主要终点是意向治疗人群术后2个月的日间动态收缩压的变化。
2016年3月11日至2020年3月13日，研究组共招募了989名参与者，其中136名受试者被随机分组，肾去神经术组69例，假手术组67例。两组患者在2个月时对联合用药的完全依从性相似，均为82%。肾去神经术组的白天动态收缩压平均降低了8 mmHg，降幅显著大于假手术组（降低3 mmHg）。两组的安全性结果没有差异。
Title: Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial
Author: 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, Kintur Sanghvi, Josh Costello, Courtney Krathan, Luot Lewis, Andrew McElvarr, John Reilly, Stephen Jenkins, Michael Cash, Shannon Williams, Maria Jarvis, Pete Fong, Cheryl Laffer, James Gainer, Mark Robbins, Sherron Crook, Sarita Maddel, David Hsi, Scott Martin, Edward Portnay, Maryanne Ducey, Suzanne Rose, Elizabeth DelMastro, Sripal Bangalore, Stephen Williams, Stanley Cabos, Carolina Rodriguez Alvarez, Thomas Todoran, Jan Basile, Eric Powers, Emily Hodskins, Vijay Paladugu, Anna Tecklenburg, Chandan Devireddy, Janice Lea, Bryan Wells, Amanda Fiebach, Claudia Merlin, Florian Rader, Suhail Dohad, Hyun-Min Kim, Mohammad Rashid, Josephine Abraham, Theophilus Owan, Anu Abraham, Iran Lavasani, Hailey Neilson, David Calhoun, Thomas McElderry, William Maddox, Suzanne Oparil, Sheila Kinder, Ajay J Kirtane, Jai Radhakrishnan, Candido Batres, Suzanne Edwards, Joseph Garasic, Doug Drachman, Randy Zusman, Kenneth Rosenfield, Danny Do, Matheen Khuddus, Suzanne Zentko, James OMeara, Ilie Barb, Abby Foster, Alice Boyette, Yale Wang, Desmond Jay, Nedaa Skeik, Robert Schwartz, Rose Peterson, Jo Anne Goldman, Jessie Goldman, Gary Ledley, Nancy Katof, Srinivasa Potluri, Scott Biedermann, Jacquelyn Ward, Megan White, Naomi DL Fisher, Laura Mauri
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.
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.
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.
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.