Transcatheter Renal Artery Sympathetic Denervation Observational Study

Hypertension, Renal Clinical Trial

Official title:

The Systemic Effects of Transcatheter Renal Artery Sympathetic Denervation Using a Second- Generation Radiofrequency Ablation Catheter: A Multicenter Observational Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05744986
• Other study ID #: 2022.273
• Status: Recruiting
• Start date: November 22, 2022
• Est. completion date: January 22, 2025

Study information

• Verified date: February 2023
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 22, 2025
• Est. primary completion date: November 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. Subject age >18.

2. Subject (or legal guardian) understands the study procedures and provides written informed consent.

3. Subject is recruited for Transcatheter Renal Denervation Procedure.

Exclusion Criteria:

There is no exclusion criteria.

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Renal

Intervention

Device:
• SYMPICITY Spyral RENAL DENERVATION (RDN) SYSTEMTM
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

Locations

Country	Name	City	State
Hong Kong	Prince of Wales Hospital	Hong Kong	Shatin
Hong Kong	Prince of Wales Hospital	Hong Kong	Shatin

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (27)

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. — View Citation

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 a — View Citation

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. eC — View Citation

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 hype — View Citation

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' — View Citation

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. d — View Citation

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 t — View Citation

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/Publi — View Citation

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. — View Citation

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 — View Citation

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 o — View Citation

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. — View Citation

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. — View Citation

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/HYPERTENSI — View Citation

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 denerva — View Citation

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 functio — View Citation

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 Societ — View Citation

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 — View Citation

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 C — View Citation

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. — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

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, Fen — View Citation

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. — View Citation

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 — View Citation

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. d — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in SBP and DBP as measured by office BP measurement and by 24 hours ABPM		24 hours
Primary	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
Primary	Changes in arterial stiffness as measured by brachial pulse wave velocity.		24 hours
Primary	Changes in serum renin/aldosterone level and 24 hours urine metanephrines		24 hours
Secondary	Change in number and dose of anti-hypertensives		6-months
Secondary	Change in renal function as measured by estimated GFR and urine albumin creatine ratio.		6-months
Secondary	Change in Patient's SF 36 survey		6-months
Secondary	Change in Hba1c		6-months
Secondary	MACE including occurrence of new myocardial infarction or stroke.		6-months
Secondary	All course morality		6-months
Secondary	Change in renal function as measured by urine albumin creatine ratio.		6-months
Secondary	Change in LDL and HDL		6-months