Renal Nerve Stimulation in Uncontrolled Hypertensive Patients Undergoing Renal Denervation (RND)

National Taiwan University

Status and phase: Enrolling; Phase 4

Conditions: Hypertension

Treatments: Procedure: nerve stimulation guided renal denervation procedure

Study type: Interventional

Funder types: Other

Identifiers

NCT05421767

201902040RINC

Details and patient eligibility

About

Study design: Investigator initiated, single center The study is aimed

1. To investigate the blood pressure (BP) change to renal nerve stimulation(RNS), and subsequently perform a renal denervation(RDN) procedure

2. to verify the cutoff value (RNS-induced systolic BP change <20 mmHg in post-RDN patients) could be a useful clinical endpoint in RDN therapy, and test the hypothesis that intense RDN could improve the efficacy of RDN.

Full description

Hypertension has become a global public health concern and associated with considerable risk of cardiovascular, cerebrovascular and kidney diseases. Although pharmacological blood pressure (BP) control can reduce these risks, BP control rates remain suboptimal. Resistant hypertension affects 10% to 15% of patients with hypertension and adequate BP control is associated with better clinical outcome of resistant hypertension. Percutaneous renal denervation system (RDN) is designed to disrupt renal afferent and efferent sympathetic nerves to modulate central sympathetic outflow and renal physiology, achieving sustained BP reduction. Although the randomized, sham-controlled trial, SYMPLICITY HTN-3 in 2014, failed to prove the effectiveness of RDN in reducing BP compared to sham procedure, three carefully designed, randomized sham-controlled RDN trials (SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, and RADIANCE-HTN SOLO), all of which showed similar and clinically meaningful BP reductions without serious adverse events. RDN, therefore, has been approved and well utilized in clinical practice to treat resistant hypertension. However,15-30% of the patients are non-responders. The reason for this is unknown. Experimental data show that renal nerve stimulation (RNS) may serve as a functional endpoint to assess completeness of the RDN procedure. Our preliminary observation study showed low RNS-induced SBP change in post-RDN patients were associated with better BP lowering response.

Our study objectives are

1. to investigate the BP change to RNS, and subsequently perform a RDN procedure

2. to verify the cutoff value (RNS-induced systolic BP change <20mmHg in post-RDN patients) could be a useful clinical endpoint in RDN therapy.

Hypotheses:

We hypothesize that an RNS-induced SBP increase of <20 mmHg in bilateral proximal main renal arteries immediately after RDN was associated with significant BP reductions 6 months following RDN. RNS-induced SBP changes could predict RDN response and even guide RDN strategies

Study design: Investigator initiated, single center, prospective study Patient population: 60 patients (20 - 80 years old) Patients with HTN.

1. 24-hour ambulatory blood pressure monitoring (ABPM) was >130 or DBP >80 mmHg

Exclusion criteria:

1. Unsuitable renal artery anatomy (main renal artery lumen diameter ≤3 mm or a total length <20 mm of the main arteries).
2. Secondary hypertension, including hyperaldosteronism, pheochromocytoma, renal artery stenosis(>50% stenosis in one or both arteries)
3. Pregnancy

Intervention:

RNS-guided RDN will be performed

1. Group A (N=35): RNS-induced SBP increase of <20 mmHg in bilateral proximal main renal arteries immediately after RDN
2. Group B(N=25): RNS-induced SBP increase of >20 mmHg in bilateral proximal main renal arteries immediately after RDN Then we will further divided Group B into Group C (N=8): observation group Group D(N=17): intensive intervention group (intensive -RDN again and the goal was post RNS-induced SBP change <20 mmHg)

Primary end-points:

The primary end points were the low RNS-induced systolic BP changes after RDN, was associated with the lower 24-hour SBP.

Enrollment: 60 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients with hypertension (HTN), including

1. 24-hour ambulatory blood pressure >130/ 80 mmHg
2. Age 20-80 years
3. Glomerular filtration rate >45 mL/min

Exclusion criteria

1. Unsuitable renal artery anatomy computed tomographic angiography (main renal artery lumen diameter ≤3 mm or a total length <20 mm of the main arteries).
2. untreated secondary HTN, including hyperaldosteronism, pheochromocytoma, renal artery stenosis(>50% stenosis)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups, including a placebo group

Low RNS-induced SBP change group

Active Comparator group

Description:

25 patients with the RNS-induced systolic BP change \<20mmHg immediately after RDN

Treatment:

Procedure: nerve stimulation guided renal denervation procedure

High RNS-induced SBP change group

Placebo Comparator group

Description:

8 patients with the RNS-induced systolic BP change \>20mmHg immediately after RDN

Treatment:

Procedure: nerve stimulation guided renal denervation procedure

intensive RDN group

Experimental group

Description:

17 patients with the initial RNS-induced systolic BP change \>20mmHg immediately after RDN, received intensive RDN therapy and let the second RNS-induced systolic BP change \< 20mmHg

Treatment:

Procedure: nerve stimulation guided renal denervation procedure