Clinical trial NCT05744986: Transcatheter Renal Artery Sympathetic Denervation Observational Study
Official title: The Systemic Effects of Transcatheter Renal Artery Sympathetic Denervation Using a Second- Generation Radiofrequency Ablation Catheter: A Multicenter Observational Study.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hypertension, Renal
Keywords: Resistant hypertension (rHT)
sympathetic nervous system (SNS)
endovascular renal denervation (RDN)
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2023-02-27
Enrollment: 100
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a feasibility study, small sample size serves as a proof of concept

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in SBP and DBP as measured by office BP measurement and by 24 hours ABPM
timeFrame: 24 hours
measure: 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.
timeFrame: 24 hours
measure: Changes in arterial stiffness as measured by brachial pulse wave velocity.
timeFrame: 24 hours
measure: Changes in serum renin/aldosterone level and 24 hours urine metanephrines
timeFrame: 24 hours
Secondary outcomes:
measure: Change in number and dose of anti-hypertensives
timeFrame: 6-months
measure: Change in renal function as measured by estimated GFR and urine albumin creatine ratio.
timeFrame: 6-months
measure: Change in Patient's SF 36 survey
timeFrame: 6-months
measure: Change in Hba1c
timeFrame: 6-months
measure: MACE including occurrence of new myocardial infarction or stroke.
timeFrame: 6-months
measure: All course morality
timeFrame: 6-months
measure: Change in renal function as measured by urine albumin creatine ratio.
timeFrame: 6-months
measure: Change in LDL and HDL
timeFrame: 6-months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: Shatin
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: Shatin
Study officials:
References:
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