Xinmai Medical's SMART Study: First-in-Class Sympathetic Mapping and Selective Renal Denervation Clinical Trial for Hypertension Designed by Chinese Scholars Published in International Cardiovascular Journal
SyMap
Innovative Device R&D Manufacturer in Cardiovascular and Respiratory Fields
SuzhouSeptember 26, 2022PR Newswire -- Recently, the registration clinical trial protocol (SMART Study: Sympathetic Mapping/Ablation Renal nerves for Treatment of hypertension Trial; NCT02761811, hereinafter referred to as the "SMART trial") for the world's first innovative / globally leading renal nerve mapping/selective ablation system for treating hypertension, developed by SyMap (Suzhou) Co., Ltd. ("SyMap"), was published in the internationally renowned cardiovascular translational research journal, *Journal of Cardiovascular Translational Research* (JCTR).[1]。
Co-Corresponding Author"SyMap" Founder: Jiangsu Provincial People's HospitalProfessor Wang Jie, Peking University First HospitalProfessor Yong Huo
Co-author: Academician of the Chinese Academy of Sciences, Zhongshan Hospital Affiliated to Fudan UniversityAcademician Ge Junbo, Peking University People's HospitalProfessor Sun Ningling、A leading authority in the cardiovascular/statistics field in ChinaProfessor Yao Chen, Professor Chen Minglong, Professor Yin Yuehui, Professor Jiang Hong, Professor Yan Xiaoyan
SyMap's Renal Nerve Mapping/Selective Ablation System is the first original clinical trial design published in an internationally renowned cardiovascular journal by Chinese scholars in the field of renal denervation using percutaneous renal artery radiofrequency ablation (RDN) for treating hypertension. The SMART trial is led by Professor Yong Huo, Professor Ningling Sun, and Academician Junbo Ge as the principal investigators.
Professor Yong Huo
Professor Yong Huo
"The SMART trial is the world's first study in the field of RDN treatment for hypertension that combines mapping with ablation. It features advanced concepts and rigorous design, utilizing devices and equipment originally developed in China, and will lead research and industrial development in this field globally."
Professor Sun Ningling
Professor Sun Ningling
"The SMART trial designed a drug composite index as the primary endpoint to address the significant clinical question of whether patients' use of antihypertensive medications changes after device-based treatment for hypertension. The trial strictly monitored participants' medication adherence; an electronic blood pressure measurement system with traceable uploads ensured the reliability of clinic blood pressure data. The academic foresight, scientific advancement, and the rigor and reliability of this trial are beyond question."
Academician Ge Junbo
Academician Ge Junbo
"Undoubtedly, SyMap's renal nerve mapping/selective ablation technology is world-leading, and we hope it will become an international benchmark for utilizing RDN to treat uncontrolled hypertension while evaluating the effectiveness of RDN during the procedure."
Renal Nerve Mapping/Theoretical Basis and Research Evidence of Selective Ablation
Currently, the overall clinical efficacy rate of RDN treatment for hypertension using any energy source is approximately 60%-65%. This is because different types of nerves are distributed around the renal arteries, but current clinical practice for RDN treatment of hypertension cannot accurately map the renal sympathetic nerves that may cause blood pressure to rise. It is precisely based on this important and unmet clinical need,"SyMap" Professor Wang Jie's team invented renal nerve mapping/Selective ablation technology, building a solid and rigorous patent system and developing a renal nerve mapping/selective ablation system to match it.
Anatomical studies have confirmed[2]Approximately 73.5% of the nerves around the renal artery are sympathetic nerves, referred to as "Hot Spots" in mapping; about 17.9% are parasympathetic nerves (also known as "sympathetic inhibitory nerves"), termed "Cold Spots"; and another 8.7% are "Neutral Spots." The relevant research findings by Professor Yin Yuehui and Professor Wang Jie's team have been published in several internationally renowned professional journals, such as Hypertension, Journal of Human Hypertension, and Current Hypertension Reports.[3,4,5], and was cited in the State-Of-Art Review on RDN published by internationally renowned authorities in JACC (Journal of the American College of Cardiology).[6]。
Further physiological studies have found that electrical stimulation of these different types of sites leads to an increase in blood pressure when stimulating the Hot Spot, a decrease in blood pressure when stimulating the Cold Spot, and no significant change in blood pressure when stimulating the Neutral Spot.
Histological studies have also demonstrated that the nerve distribution around the renal arteries is directly related to Strong Response Sites (SRS, sites where electrical stimulation of the renal nerves increases systolic blood pressure by more than 10 mmHg) and Weak Response Sites (WRS, sites where electrical stimulation of the renal nerves increases systolic blood pressure by no more than 10 mmHg). The number of nerves and the total cross-sectional area of nerves in regions adjacent to SRS are significantly greater than those surrounding WRS.
AboutSMART Trial
The renal artery mapping and radiofrequency ablation catheter developed by "SyMap" and the accompanying mapping and radiofrequency ablation device (Renal Nerve Mapping/Selective Ablation System SyMapCath®™ /SymPioneer®™), integrating functions such as guidance, imaging, stimulation, temperature-controlled ablation, and manual perfusion. The renal nerve mapping/selective ablation procedure starts from the distal renal artery and implements the surgical steps point by point: electrical stimulation/mapping - ablation - re-stimulation/confirmation. Blood pressure/heart rate changes are monitored when electrical stimulation is applied within the renal artery. If blood pressure/heart rate increases, it is considered a hotspot for ablation; otherwise, the procedure moves to the next site. After each ablation, post-stimulation is performed to confirm whether the ablation is complete. Through the above method, mapping and ablation are carried out site by site from the distal to the proximal renal artery to achieve targeted removal of renal sympathetic nerves, preserve other types of nerves, and allow for immediate verification of the surgical effect on the operating table.
Based on the above innovative concepts, theoretical foundations, experimental evidence, equipment, and methods,Professor Wang Jie's team and Professors Huo Yong, Ge Junbo, Sun Ningling, Chen Minglong, Jiang Hong, Yao Chen, Yin Yuehui, Lu Chengzhi, Yan XiaoyanCollaborated, designed, and led the organization of the SMART trial.
The SMART trial is a prospective, multicenter, single-blind, randomized controlled study designed to validate the safety and efficacy of a novel renal nerve mapping/selective ablation system for treating hypertension as part of a clinical registry trial. The renal nerve mapping/selective ablation system used in the trial can map renal sympathetic/parasympathetic nerve sites and selectively remove renal sympathetic nerves, allowing immediate determination of surgical outcomes during the procedure and confirmation of whether renal sympathetic nerves have been effectively removed. A total of 220 patients whose blood pressure remained uncontrolled after taking at least two antihypertensive medications for 28 days were randomly assigned to either the RDN surgery group (n=110) or the Sham surgery group (n=110). The trial employs a dual clinical endpoint design, with primary endpoints including the office systolic blood pressure (SBP) target achievement rate (<140mmHg) and a composite index of antihypertensive medication use at 6 months post-surgery. The SMART study is currently the only prospective large-scale clinical study in the RDN field that can answer how many fewer antihypertensive medications hypertensive patients can take after undergoing RDN surgery. This advanced concept was first proposed worldwide by SyMap, and this innovative academic concept and design have been adopted by European and American scholars and international large-scale clinical research in recent years. Medtronic also introduced the Drug Burden Index to analyze the results of its SPYRAL HTN-ON MED study.[7]SyMap once invited renowned experts from China's cardiovascular and statistical fields to analyze Medtronic's use of "win ratio" and the introduction of drug index in "Spyral On-Med".The research results have been interpreted (click to view).The breakthrough clinical primary endpoint design concept of the drug index is highly compatible with China's clinical needs, as medication adherence among hypertensive patients in China is generally poor. It is extremely challenging to control participants' self-adjustment of antihypertensive drugs in clinical trials. If Medtronic’s trial protocol were directly copied, the feasibility would be weak and pose significant risks. The SMART trial’s clinical protocol was designed based on real-world complex clinical practice scenarios. It specifies the types, dosages, and manufacturers (all drugs supplied by SyMap) of antihypertensive medications taken by patients during the trial, along with clear rules for adjusting medications when necessary (see figure below). Additionally, LC-MS/MS methods were used to rigorously monitor participants’ medication adherence throughout the trial.[8], thereby eliminating the interference of antihypertensive drugs on the efficacy of RDN procedures. The rigorous and scientifically designed protocol, which aligns with clinical realities, along with stringent operational guidelines, ensured the exceptionally high quality of the SMART trial.
The SMART trial, which lasted for about six years, completed the enrollment of all 220 patients in February this year with the strong support of more than ten top tertiary hospitals in China, and finished the six-month postoperative follow-up for all patients in August. We look forward to the early publication of the results of the SMART trial, further solidifying and improving the evidence chain for RDN treatment of hypertension based in China, showcasing high-quality original research results from China to the world, and bringing new, safe, and effective treatment options to hypertension patients worldwide!
The publication of the SMART trial clinical protocol in JCTR represents that "SyMap" has further gained international academic recognition for the clinical research conducted in the field of RDN treatment for hypertension. It consolidates the status of the SMART trial in anatomy, physiology, histology, and clinical evidence-based medicine, marking a solid step forward in perfecting the evidence chain for renal artery mapping/selective ablation in the treatment of hypertension. This holds significant importance in the clinical research of RDN treatment for hypertension and stands as another contribution made by Chinese scholars in this field.
Made in China,The Leader in Evidence-Based Development of RDN
In the current stage of RDN academic development, many areas of relevant evidence-based medicine are still "uncharted territories." The design and implementation of the SMART trial once again demonstrate Chinese doctors' and scholars' ability to pioneer new fields and concepts.
From the construction of the technology platform, clinical research design to surgical methods, every step and every detail of the SMART trial has been led by Chinese doctors and experts. The successful progress of this study demonstrates that Chinese hypertension diagnosis and treatment experts are making their voices heard in the RDN field and establishing new concepts based on Chinese research.Not only at the forefront of the world, but also establishing a solid scientific evidence base for Chinese scholars to take a leading position in this field., hoping that in the future, European and American peers will cite the work, data, evidence, and guidelines based on clinical research in China in this field.
References:
[1]. Wang J, Sun N, Ge J, Jiang H et al：Rationale and Design of Sympathetic Mapping/Ablation of Renal Nerves Trial For Treatment of Hypertension (SMART Study): A Prospective, Multicenter, Single Blind, Randomized and Sham Procedure Controlled Study. J Cardiovascular Translational Res 2022, Aug 30. doi: 10.1007/s12265-022-10307-z. Online ahead of print.
[2]. van Amsterdam WA, Blankestijn PJ, Goldschmeding R, et al. The morphological substrate for renal denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study. Ann Anat. 2016；204: 71-79.
[3]. Fudim M, Sobotka AA, Yin YH, et al. Selective vs. global Renal Denervation: a case for less is more. Curr Hypertension Rep. 2018；20: 37.
[4]. Liu H, Chen W, Lai Y, et al. Selective Renal Denervation guided by renal nerve stimulation in canine: a method for identification of optimal ablation target. Hypertension. 2019；74: 536-545.
[5]. Tan K, Lai Y, Chen W, et al. Selective renal denervation guided by renal nerve stimulation: mapping renal nerves for unmet clinical needs. J Hum Hypertension. 2019；33: 716-724.
[6]. Kiuchi MG, Esler MD, Fink GD, et al. Renal denervation update from the international sympathetic nervous system summit: JACC State-of-the-Art review. J Am Coll Cardiol. 2019；73: 3006-3017.
[7]. Kandzari DE et al: EuroIntervention 2021;16(18): e1496-e1502
[8]. Wang Y, Wang JW, Wang Y et al: Monitoring Antihypertensive Medication Adherence by LC-MS/MS: Method Establishment and Clinical Application. J Cardiovasc Pharmacol 2021; 78(4): 581–596
To read the full text of this paper, click to download.
About SyMap
"SyMap" is an internationally leading company focused on the research, development, and application of breakthrough innovative minimally invasive interventional technologies to treat major diseases in the cardiovascular and respiratory fields. It has a robust product pipeline at various stages of development: its world-first/global-leading renal nerve mapping/selective ablation system, SyMapCath, is designed for treating hypertension.®™/SymPioneer®™, which is expected to be approved by NMPA in 2023 through the special approval process for innovative medical devices. Its bronchoscopic radiofrequency ablation system Elation is used for treating severe asthma.®™It is the only product in this field approved by the NMPA to enter the special review process for innovative medical devices and is expected to be approved for marketing in 2024. The world's first Precisely Controlled, Hypertonic Solution Assisted RF System ("Zedan" system) developed for the treatment of early-stage lung cancer via bronchoscopy has completed the First in Human (FIH) clinical study in Australia. Recently, preliminary efficacy and safety results of the "Zedan" system in treating early-stage lung tumors were announced at the 32nd European Respiratory Society (ERS) Annual Congress.
"SyMap" relies on a team of professional talents with internationally advanced levels and collaborates with world-renowned clinical scientists and researchers through disruptive minimally invasive interventional treatment technologies. "Leveraging China to impact the world," it aims to serve global patients with China's original disruptive products and has become an international leader in treating major cardiovascular and respiratory diseases using active minimally invasive interventional methods.
Further Reading
For Study·RDN｜Application of Renal Nerve Mapping Before, During, and After Renal Denervation: SyMap
Seeking Truth·RDN | How to Design RDN Clinical Trials That Meet International Standards?