Safety and Efficacy of Ultrasound Renal Denervation in Kidney Transplantation Patients With Uncontrolled Hypertension

Official title

Safety and Efficacy of Ultrasound Renal Denervation in Kidney Transplantation Patients With Uncontrolled Hypertension: the RESTART Study

Overview

This prospective, single-arm, interventional study is designed to assess the short-term and long-term safety and efficacy of bilateral ultrasound renal sympathetic denervation (RDN) of the native kidneys in renal transplant patients with uncontrolled hypertension. Objectives: * To assess the short-term and long-term changes in ambulatory and office blood pressure (BP) following native kidney RDN in renal transplant patients * To assess the long-term safety of native kidney RDN in renal transplant patients * To assess the short-term and long-term change in antihypertensive drug prescriptions following native kidney RDN in renal transplant patients * To assess the short-term and long-term change in adherence to antihypertensive drugs following native kidney RDN in renal transplant patients

Detailed description

The RESTART study is an investigator-initiated, prospective, single-center, single-arm interventional study investigating the safety and efficacy of bilateral native kidney RDN in 40 renal transplant patients with uncontrolled hypertension despite antihypertensive medication (or with a documented intolerance to antihypertensive drugs).

Previously, RDN demonstrated to safely reduce BP as compared to sham-control in multiple randomized clinical trials, both in patients with and without concomitant antihypertensive medication. Up until now, patients with a history of renal failure or kidney transplantation have been excluded from these studies. As the pathophysiology of hypertension is considered different in hypertensive renal transplant patients as compared to the previously studied populations (without kidney transplantation), the effect of native kidney RDN in hypertensive patients with a history of kidney transplantation remains unknown. The current study aims to provide novel insights on the safety and efficacy of RDN in this particular population. Adjustment for routine therapy adherence will also be performed as this proved to be an important confounding factor in previous research.

Interventions

• Device Paradise® ultrasound renal denervation system.
  Bilateral renal sympathetic denervation of the native kidneys using the Paradise® ultrasound renal denervation system.

Primary outcome measures

• Efficacy: change in mean 24-hour ambulatory systolic blood pressure [Time frame: Baseline vs. 3-month follow-up]
• Safety: occurrence of the composite endpoint [Time frame: Baseline vs. 3-month follow-up]

Secondary outcome measures (12)

• Efficacy: change in mean 24-hour ambulatory diastolic blood pressure [Time frame: Baseline vs. 3-month follow-up]
• Efficacy: change in daytime ambulatory systolic and diastolic blood pressure [Time frame: Baseline vs. 3-month follow-up]
• Efficacy: change in nighttime ambulatory systolic and diastolic blood pressure [Time frame: Baseline vs. 3-month follow-up]
• Efficacy: change in office systolic and diastolic blood pressure [Time frame: Baseline vs. 3-month follow-up]
• Efficacy: changes in ambulatory (mean 24-hour, daytime, nighttime) systolic and diastolic blood pressure [Time frame: Baseline vs. 3-month follow-up]
• Efficacy: changes in office systolic and diastolic blood pressure [Time frame: Baseline vs. 3-month follow-up]
• Efficacy: changes in the number of prescribed defined daily dosages and number of classes of antihypertensive drugs [Time frame: Baseline vs. 3-month follow-up]
• Efficacy: change in the percentage therapy adherence [Time frame: Baseline vs. 3-month follow-up]
• Efficacy: annual changes in ambulatory (mean 24-hour, daytime, nighttime) systolic and diastolic blood pressure [Time frame: Baseline up until and including 5-year follow-up]
• Efficacy: annual changes in office systolic and diastolic blood pressure [Time frame: Baseline up until and including 5-year follow-up]
• Efficacy: annual changes in in the number of prescribed defined daily dosages and number of classes of antihypertensive drugs [Time frame: Baseline up until and including 5-year follow-up]
• Efficacy: annual change in the percentage therapy adherence [Time frame: Baseline up until and including 5-year follow-up]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Kidney transplantation ≥ 12 months ago with stable immunosuppressive drug treatment
• Estimated Glomerular Filtration Rate (eGFR) ≥ 40 ml/min/1.73m2
• Office systolic BP ≥ 140 mmHg and a mean 24-hour ambulatory systolic BP ≥ 130 mmHg at screening
• Antihypertensive medication regimen:

• Stable regimen of at least two antihypertensive drugs of different classes, including a diuretic (defined a thiazide diuretic, loop diuretic or mineralocorticoid receptor antagonist), for at least three months, or
• Documented intolerance to three classes of antihypertensive drugs, and
• A change in antihypertensive drug regimen is not anticipated within the oncoming three months.
• Patient is willing and able to provide written informed consent

Exclusion criteria

• Native renal artery anatomy not eligible for RDN, defined as at least one of the following conditions:

• History of renal artery stenting or angioplasty
• History of renal denervation
• History of kidney tumors
• Renal artery diameter < 3 mm or > 8 mm
• Renal artery length < 20 mm
• Fibromuscular disease (FMD) of the native renal arteries
• Renal artery aneurysm
• Renal artery stenosis > 30%
• Presence of a remnant transplant kidney after re-transplantation or absence of native kidneys
• Solitary native kidney
• History of intravenous contrast dye allergy or nephropathy
• Iliac/femoral artery stenosis precluding insertion of the Paradise catheter
• Uncorrected, treatable secondary cause of hypertension
• Pregnancy
• Life expectancy < one year at the discretion of the investigator

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• Erasmus University Medical Center — Rotterdam

Identifiers

NCT: NCT05934383 · RESTART - renal denervation

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗