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Transcatheter Renal Artery Sympathetic Denervation Observational Study

Recruiting
Conditions
Hypertension, Renal
Registration Number
NCT05744986
Lead Sponsor
Chinese University of Hong Kong
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.

Detailed 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 & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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.
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Exclusion Criteria

There is no exclusion criteria.

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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Changes in SBP and DBP as measured by office BP measurement and by 24 hours ABPM24 hours
Changes in arterial stiffness as measured by brachial pulse wave velocity.24 hours
Changes in serum renin/aldosterone level and 24 hours urine metanephrines24 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
Secondary Outcome Measures
NameTimeMethod
Change in Patient's SF 36 survey6-months
Change in LDL and HDL6-months
All course morality6-months
Change in number and dose of anti-hypertensives6-months
Change in renal function as measured by estimated GFR and urine albumin creatine ratio.6-months
Change in Hba1c6-months
MACE including occurrence of new myocardial infarction or stroke.6-months
Change in renal function as measured by urine albumin creatine ratio.6-months

Trial Locations

Locations (1)

Prince of Wales Hospital

🇭🇰

Hong Kong, Shatin, Hong Kong

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