Clinical trial NCT05421767: Renal Nerve Stimulation in Uncontrolled Hypertensive Patients Undergoing Renal Denervation
Official title: National Tawan University Hospital
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hypertension
Keywords: renal nerve stimulation
renal nerve denervation
Sympathetic nerve activity
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2022-06-16
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RNS checked RDN
Primary purpose: TREATMENT

Brief summary: 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

1) 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.

Detailed 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

1) 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.

Eligibility criteria: 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)

Primary outcomes:
measure: arterial blood pressure response
timeFrame: during procedure
Secondary outcomes:
measure: blood pressure at 6 months
timeFrame: 6 months after the intervention
measure: blood pressure at 12 months
timeFrame: 12 months after the intervention
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References:
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