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

Hypertension Clinical Trial

— RESTART  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05934383
• Other study ID #: RESTART
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2023
• Est. completion date: September 2030

Study information

• Verified date: July 2023
• Source: Erasmus Medical Center
• Contact: Joost Daemen, MD PhD
• Phone: +31107040704
• Email: j.daemen[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: September 2030
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Kidney Transplantation

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	ReCor Medical, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: change in mean 24-hour ambulatory systolic blood pressure		Baseline vs. 3-month follow-up
Primary	Safety: occurrence of the composite endpoint	Consisting of (whichever occurs first): All-cause mortality; New onset (acute) end-stage renal disease (eGFR< 15 mL/min/m2 or need for renal replacement therapy); Significant embolic event resulting in end-organ damage; Renal artery perforation requiring an invasive intervention; Renal artery dissection requiring an invasive intervention; Major vascular complications; Hospitalization for hypertensive or hypotensive crisis	Baseline vs. 3-month follow-up
Secondary	Efficacy: change in mean 24-hour ambulatory diastolic blood pressure		Baseline vs. 3-month follow-up
Secondary	Efficacy: change in daytime ambulatory systolic and diastolic blood pressure		Baseline vs. 3-month follow-up
Secondary	Efficacy: change in nighttime ambulatory systolic and diastolic blood pressure		Baseline vs. 3-month follow-up
Secondary	Efficacy: change in office systolic and diastolic blood pressure		Baseline vs. 3-month follow-up
Secondary	Efficacy: changes in ambulatory (mean 24-hour, daytime, nighttime) systolic and diastolic blood pressure	In a subpopulation of patients with an equal level of therapy adherence at both timepoints	Baseline vs. 3-month follow-up
Secondary	Efficacy: changes in office systolic and diastolic blood pressure	In a subpopulation of patients with an equal level of therapy adherence at both timepoints	Baseline vs. 3-month follow-up
Secondary	Efficacy: changes in the number of prescribed defined daily dosages and number of classes of antihypertensive drugs		Baseline vs. 3-month follow-up
Secondary	Efficacy: change in the percentage therapy adherence	The percentage adherence will be calculated as the proportion of drugs that could be detected using dried blood spot testing out of all drugs prescribed to the patient at the time of the testing.	Baseline vs. 3-month follow-up
Secondary	Efficacy: annual changes in ambulatory (mean 24-hour, daytime, nighttime) systolic and diastolic blood pressure		Baseline up until and including 5-year follow-up
Secondary	Efficacy: annual changes in office systolic and diastolic blood pressure		Baseline up until and including 5-year follow-up
Secondary	Efficacy: annual changes in in the number of prescribed defined daily dosages and number of classes of antihypertensive drugs		Baseline up until and including 5-year follow-up
Secondary	Efficacy: annual change in the percentage therapy adherence	The percentage adherence will be calculated as the proportion of drugs that could be detected using dried blood spot testing out of all drugs prescribed to the patient at the time of the testing.	Baseline up until and including 5-year follow-up
Secondary	Safety: the number of patients in whom no successful bilateral renal denervation procedure can be performed	E.g. due to anatomical difficulties	Periprocedural
Secondary	Safety: change in renal function (estimated Glomerular Filtration Rate)		Baseline vs. 3-month follow-up
Secondary	Safety: change in renal function (urine protein/creatinine ratio)		Baseline vs. 3-month follow-up
Secondary	Safety: occurrence of the individual components of the primary safety outcome	All-cause mortality; New onset (acute) end-stage renal disease (eGFR< 15 mL/min/m2 or need for renal replacement therapy); Significant embolic event resulting in end-organ damage; Renal artery perforation requiring an invasive intervention; Renal artery dissection requiring an invasive intervention; Major vascular complications; Hospitalization for hypertensive or hypotensive crisis	Baseline up until and including 5-year follow-up
Secondary	Safety: occurrence of any major adverse cardiovascular and cerebrovascular event (MACCE)	Including myocardial infarction, coronary revascularization, stroke and cardiovascular mortality	Baseline up until and including 5-year follow-up
Secondary	Safety: occurrence of the individual components of major adverse cardiovascular and cerebrovascular event (MACCE)	Including myocardial infarction, coronary revascularization, stroke and cardiovascular mortality	Baseline up until and including 5-year follow-up
Secondary	Safety: annual change in renal function (estimated Glomerular Filtration Rate)		Baseline up until and including 5-year follow-up
Secondary	Safety: annual change in renal function (urine protein/creatinine ratio)		Baseline up until and including 5-year follow-up