Transcatheter Renal Artery Sympathetic Denervation Observational Study

NCT05744986 | Unknown

• 1 other identifier: 2022.273
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

Hypertension is a common health problem that affects millions of people in the world. Poorly controlled blood pressure (BP) leads to cardiovascular, cerebrovascular and renal complications. Despite the availability of multitudes of anti-hypertensive drugs, the percentage of patients achieving optimal control of hypertension has remained disappointingly low. Resistant hypertension (rHT) is defined as the failure to achieve target BP despite concurrent use of antihypertensive drugs of different classes, with one of them being diuretics. The reported prevalence of this condition ranged from 5 to 30%. Lifestyle modification, enhancing drug compliance, treating of secondary causes, or adding mineralocorticoid receptor antagonist such as spironolactone or eplerenone are well established strategies to treat resistant hypertension. Besides factors such as, activated sympathetic nervous system (SNS) and increased sympathetic outflow was thought to contribute to the development of rHT as well. Autonomic sympathectomy by way of endovascular renal denervation (RDN) was once a hopeful candidate as an adjuvant treatment for patients with rHT and it had shown signals of efficacy in early trials. However, the blood-pressure lowering efficacy was not demonstrated in the larger-scaled, randomized, sham- controlled SYMPLICITY HTN-3 trial. One possible explanation of the lack of efficacy of RDN in this trial was the lower-than-expected BP responses in the RDN group and higher than-expected BP reduction in the control group which raised the speculation that some of the patients recruited were not true rHT as the trial intended to include. The suboptimal anti-hypertensive efficacy of RDN in HTN-3 was also partly attributed to the design of the first-generation RDN catheter, in which only a single electrode is deployed and might not offer sufficient sympathetic denervation as less than half of patients in the SYMPLICITY HTN-3 received 4 quadrants ablation. The second generation SYMPLICITY RDN catheterTM has 4 times electrodes that are arranged in spirally in 90-degree intervals. Theoretically, the newer generation catheter can provide more efficient and extensive denervation in a shorter period of time. Its efficacy was confirmed in SYMPLICITY HTN ON-MED and OFF-MED trial, which confirmed a consistent and durable BP reduction that lasted into 36 months with or without adjuvant anti-hypertensive drugs. BP reduction is only one of the effects of RDN. Previous observational studies of the first generation RDN catheter have shown an inconsistent effect of RDN in left ventricular (LV) remodelling, arrythmia modulation, arterial de-stiffening and quality of life. No report of these effects has been published with the newer generation catheter. Furthermore, vigorous efforts have been put into searching for clinical predictors that can identify patients in whom the BP reduction effect of RDN is most significant. This study aims to investigate the systemic effects of RDN using the new generation SYMLICITY RDN catheterTM in patients with rHT.

Conditions

Hypertension, Renal

Keywords

Resistant hypertension (rHT); sympathetic nervous system (SNS); endovascular renal denervation (RDN)

Outcome Measures

Primary Outcomes (4)

• Changes in SBP and DBP as measured by office BP measurement and by 24 hours ABPM

  24 hours

• Changes in Echocardiographic parameters including LV wall thickness, LV mass, LV dimension, LV systolic function, LV diastolic function, LV global longitudinal strain, LA volume, LA strain, descending aortic circumferential strain, and RV function.

  24 hours

• Changes in arterial stiffness as measured by brachial pulse wave velocity.

  24 hours

• Changes in serum renin/aldosterone level and 24 hours urine metanephrines

  24 hours

Secondary Outcomes (8)

• Change in number and dose of anti-hypertensives

  6-months

• Change in renal function as measured by estimated GFR and urine albumin creatine ratio.

  6-months

• Change in Patient's SF 36 survey

  6-months

• Change in Hba1c

  6-months

• MACE including occurrence of new myocardial infarction or stroke.

  6-months

Interventions

SYMPICITY Spyral RENAL DENERVATION (RDN) SYSTEMTM DEVICE

The second generation SYMPLICITY RDN catheterTM has 4 times electrodes that are arranged in spirally in 90-degree intervals. Theoretically, the newer generation catheter can provide more efficient and extensive denervation in a shorter period of time16. Its efficacy was confirmed in SYMPLICITY HTN ON-MED and OFF-MED trial, which confirmed a consistent and durable BP reduction that lasted into 36 months with or without adjuvant anti-hypertensive drugs

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a feasibility study, small sample size serves as a proof of concept

You may qualify if:

• Subject age \>18.
• Subject (or legal guardian) understands the study procedures and provides written informed consent.
• Subject is recruited for Transcatheter Renal Denervation Procedure.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (2)

Prince of Wales Hospital

Hong Kong, Shatin, 0000, Hong Kong

RECRUITING

Prince of Wales Hospital

Hong Kong, Shatin, 0000, Hong Kong

RECRUITING

Related Publications (27)

• Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. doi: 10.1016/S0140-6736(05)17741-1.

  PMID: 15652604 RESULT

• Whitworth JA; World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003 Nov;21(11):1983-92. doi: 10.1097/00004872-200311000-00002.

  PMID: 14597836 RESULT

• Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):1269-1324. doi: 10.1161/HYP.0000000000000066. Epub 2017 Nov 13. No abstract available.

  PMID: 29133354 RESULT

• Carey RM, Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR, Egan BM, Flack JM, Gidding SS, Judd E, Lackland DT, Laffer CL, Newton-Cheh C, Smith SM, Taler SJ, Textor SC, Turan TN, White WB; American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. 2018 Nov;72(5):e53-e90. doi: 10.1161/HYP.0000000000000084.

  PMID: 30354828 RESULT

• Carey RM, Sakhuja S, Calhoun DA, Whelton PK, Muntner P. Prevalence of Apparent Treatment-Resistant Hypertension in the United States. Hypertension. 2019 Feb;73(2):424-431. doi: 10.1161/HYPERTENSIONAHA.118.12191.

  PMID: 30580690 RESULT

• Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM; American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008 Jun 24;117(25):e510-26. doi: 10.1161/CIRCULATIONAHA.108.189141.

  PMID: 18574054 RESULT

• Anderson EA, Sinkey CA, Lawton WJ, Mark AL. Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. Hypertension. 1989 Aug;14(2):177-83. doi: 10.1161/01.hyp.14.2.177.

  PMID: 2759678 RESULT

• SMITHWICK RH, THOMPSON JE. Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc. 1953 Aug 15;152(16):1501-4. doi: 10.1001/jama.1953.03690160001001. No abstract available.

  PMID: 13061307 RESULT

• Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011 May;57(5):911-7. doi: 10.1161/HYPERTENSIONAHA.110.163014. Epub 2011 Mar 14.

  PMID: 21403086 RESULT

• Symplicity HTN-2 Investigators; Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010 Dec 4;376(9756):1903-9. doi: 10.1016/S0140-6736(10)62039-9. Epub 2010 Nov 17.

  PMID: 21093036 RESULT

• Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, Leon MB, Liu M, Mauri L, Negoita M, Cohen SA, Oparil S, Rocha-Singh K, Townsend RR, Bakris GL; SYMPLICITY HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014 Apr 10;370(15):1393-401. doi: 10.1056/NEJMoa1402670. Epub 2014 Mar 29.

  PMID: 24678939 RESULT

• Tam GM, Yan BP, Shetty SV, Lam YY. Transcatheter renal artery sympathetic denervation for resistant hypertension: an old paradigm revisited. Int J Cardiol. 2013 Apr 15;164(3):277-81. doi: 10.1016/j.ijcard.2012.01.048. Epub 2012 Feb 14.

  PMID: 22336259 RESULT

• Bakris GL, Townsend RR, Flack JM, Brar S, Cohen SA, D'Agostino R, Kandzari DE, Katzen BT, Leon MB, Mauri L, Negoita M, O'Neill WW, Oparil S, Rocha-Singh K, Bhatt DL; SYMPLICITY HTN-3 Investigators. 12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: the SYMPLICITY HTN-3 trial. J Am Coll Cardiol. 2015 Apr 7;65(13):1314-1321. doi: 10.1016/j.jacc.2015.01.037.

  PMID: 25835443 RESULT

• Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, Flack JM, Katzen BT, Lea J, Lee DP, Leon MB, Ma A, Massaro J, Mauri L, Oparil S, O'Neill WW, Patel MR, Rocha-Singh K, Sobotka PA, Svetkey L, Townsend RR, Bakris GL. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J. 2015 Jan 21;36(4):219-27. doi: 10.1093/eurheartj/ehu441. Epub 2014 Nov 16.

  PMID: 25400162 RESULT

• Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, Ewen S, Tsioufis K, Tousoulis D, Sharp ASP, Watkinson AF, Schmieder RE, Schmid A, Choi JW, East C, Walton A, Hopper I, Cohen DL, Wilensky R, Lee DP, Ma A, Devireddy CM, Lea JP, Lurz PC, Fengler K, Davies J, Chapman N, Cohen SA, DeBruin V, Fahy M, Jones DE, Rothman M, Bohm M; SPYRAL HTN-OFF MED trial investigators*. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017 Nov 11;390(10108):2160-2170. doi: 10.1016/S0140-6736(17)32281-X. Epub 2017 Aug 28.

  PMID: 28859944 RESULT

• Bohm M, Kario K, Kandzari DE, Mahfoud F, Weber MA, Schmieder RE, Tsioufis K, Pocock S, Konstantinidis D, Choi JW, East C, Lee DP, Ma A, Ewen S, Cohen DL, Wilensky R, Devireddy CM, Lea J, Schmid A, Weil J, Agdirlioglu T, Reedus D, Jefferson BK, Reyes D, D'Souza R, Sharp ASP, Sharif F, Fahy M, DeBruin V, Cohen SA, Brar S, Townsend RR; SPYRAL HTN-OFF MED Pivotal Investigators. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020 May 2;395(10234):1444-1451. doi: 10.1016/S0140-6736(20)30554-7. Epub 2020 Mar 29.

  PMID: 32234534 RESULT

• Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, Tsioufis K, Tousoulis D, Choi JW, East C, Brar S, Cohen SA, Fahy M, Pilcher G, Kario K; SPYRAL HTN-ON MED Trial Investigators. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018 Jun 9;391(10137):2346-2355. doi: 10.1016/S0140-6736(18)30951-6. Epub 2018 May 23.

  PMID: 29803589 RESULT

• Mahfoud F, Kandzari DE, Kario K, Townsend RR, Weber MA, Schmieder RE, Tsioufis K, Pocock S, Dimitriadis K, Choi JW, East C, D'Souza R, Sharp ASP, Ewen S, Walton A, Hopper I, Brar S, McKenna P, Fahy M, Bohm M. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet. 2022 Apr 9;399(10333):1401-1410. doi: 10.1016/S0140-6736(22)00455-X. Epub 2022 Apr 4.

  PMID: 35390320 RESULT

• Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, Hoppe UC. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012 Mar 6;59(10):901-9. doi: 10.1016/j.jacc.2011.11.034.

  PMID: 22381425 RESULT

• Schirmer SH, Sayed MM, Reil JC, Ukena C, Linz D, Kindermann M, Laufs U, Mahfoud F, Bohm M. Improvements in left ventricular hypertrophy and diastolic function following renal denervation: effects beyond blood pressure and heart rate reduction. J Am Coll Cardiol. 2014 May 13;63(18):1916-23. doi: 10.1016/j.jacc.2013.10.073. Epub 2013 Dec 4.

  PMID: 24315919 RESULT

• Mahfoud F, Urban D, Teller D, Linz D, Stawowy P, Hassel JH, Fries P, Dreysse S, Wellnhofer E, Schneider G, Buecker A, Schneeweis C, Doltra A, Schlaich MP, Esler MD, Fleck E, Bohm M, Kelle S. Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial. Eur Heart J. 2014 Sep 1;35(33):2224-31b. doi: 10.1093/eurheartj/ehu093. Epub 2014 Mar 6.

  PMID: 24603307 RESULT

• Ukena C, Bauer A, Mahfoud F, Schreieck J, Neuberger HR, Eick C, Sobotka PA, Gawaz M, Bohm M. Renal sympathetic denervation for treatment of electrical storm: first-in-man experience. Clin Res Cardiol. 2012 Jan;101(1):63-7. doi: 10.1007/s00392-011-0365-5. Epub 2011 Sep 29.

  PMID: 21960416 RESULT

• Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger HR, Wirth K, Bohm M. Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea. Hypertension. 2012 Jul;60(1):172-8. doi: 10.1161/HYPERTENSIONAHA.112.191965. Epub 2012 May 14.

  PMID: 22585944 RESULT

• Peters CD, Mathiassen ON, Vase H, Bech Norgaard J, Christensen KL, Schroeder AP, Rickers HJVH, Opstrup UK, Poulsen PL, Langfeldt S, Andersen G, Hansen KW, Botker HE, Engholm M, Bertelsen JB, Pedersen EB, Kaltoft A, Buus NH. The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial). Blood Press. 2017 Dec;26(6):366-380. doi: 10.1080/08037051.2017.1368368. Epub 2017 Aug 23.

  PMID: 28830251 RESULT

• Berukstis A, Navickas R, Neverauskaite-Piliponiene G, Ryliskyte L, Misiura J, Vajauskas D, Misonis N, Laucevicius A. Arterial Destiffening Starts Early after Renal Artery Denervation. Int J Hypertens. 2019 Mar 3;2019:3845690. doi: 10.1155/2019/3845690. eCollection 2019.

  PMID: 30941209 RESULT

• Krawczyk-Ozog A, Tokarek T, Moczala K, Siudak Z, Dziewierz A, Mielecki W, Gorecki T, Gerba K, Dudek D. Long-term quality of life and clinical outcomes in patients with resistant hypertension treated with renal denervation. Postepy Kardiol Interwencyjnej. 2016;12(4):329-333. doi: 10.5114/aic.2016.63633. Epub 2016 Nov 17.

  PMID: 27980546 RESULT

• Mitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, Horton K, Ogunyankin KO, Palma RA, Velazquez EJ. Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults: Recommendations from the American Society of Echocardiography. J Am Soc Echocardiogr. 2019 Jan;32(1):1-64. doi: 10.1016/j.echo.2018.06.004. Epub 2018 Oct 1. No abstract available.

  PMID: 30282592 RESULT

MeSH Terms

Conditions

Hypertension, Renal

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 27, 2023
• Study Start: November 22, 2022
• Primary Completion: November 22, 2024
• Study Completion: January 22, 2025
• Last Updated: February 27, 2023

Record last verified: 2023-02

Locations

HK (2)