A Study of Non-Vascular Renal Denervation Using the Verve Medical Phoenix ™ System (TUSK)

Trans Ureteral Sympathectomy of the Kidney Study Using the Verve Medical Phoenix ™ System

The aim of the study is to assess the safety and effectiveness of a novel device for renal denervation to lower blood pressure in people with uncontrolled hypertension. Prior studies demonstrate the potential benefit of renal denervation in hypertension, though these studies primarily denervate the kidneys by passing catheters through the arteries in the groin into the renal arteries. The TUSK study utilizes the Phoenix system to perform denervation by advancing the device (a thin electrode) through the urinary tract into the kidneys where radiofrequency energy is briefly applied to denervate the kidneys.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension; Uncontrolled Hypertension
• Intervention / Treatment: Device: Renal Pelvic Denervation (bilateral)

Detailed Description

Up to 20 patients with uncontrolled hypertension will be treated with the PhoenixTM renal pelvic denervation system, whether or not receiving background medical therapy.

Qualification will be based on documented uncontrolled hypertension by 24-hour ambulatory blood pressure monitoring. Those qualifying will be expected to maintain their medical therapy without changes until after the primary effectiveness assessment two months later.

Following baseline testing, patients will undergo renal pelvic denervation under anesthesia and remain in the hospital overnight. The denervation device is inserted through the urethra into each kidney and all devices are removed at the completion of the procedure. Radiofrequency energy is administered for a single 2-minute treatment period in each kidney.

Follow up visits will extend to one year. Patients will complete medication logs along with repeat assessment of blood pressure in office and via 24-hour ambulatory blood pressure monitor. Follow up testing will also include imaging studies of the kidneys.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia
    • Pineo Medical Ecosystem
  • Tbilisi, Georgia
    • Israeli-Georgian Medical Research Clinic Helsicore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Off-med group: (1) Ambulatory mean daytime SBP ≥140 mmHg in patients never treated for hypertension or after being taken off anti-hypertension medications for 4 weeks before ambulatory blood pressure assessment. (2) Ambulatory daytime SBP and DBP less than 170/105 mmHg. (3) Subjects will not be on ANY anti-hypertension medications or will be willing to discontinue current anti-hypertension medications.
• On-med group: (1) Subjects who are currently taking 1, 2, or 3 anti-hypertensive medications. (2) Ambulatory mean daytime SBP ≥135 mmHg. (3) Ambulatory daytime SBP and DBP less than 170/105 mmHg.

Exclusion Criteria:

• Females who are either pregnant or breastfeeding.
• Office SBP or DBP ≥180/110 mmHg.
• Untreated urinary tract infection.
• Renal collecting system is compromised, and subject cannot undergo routine cystoscopy and retrograde pyelogram.
• Dialysis patients.
• Renal transplant patients.
• Subjects on the following medications, clonidine, guanfacine and methyldopa.
• Known secondary causes of hypertension such as adrenal disease, renal artery stenosis, renovascular hypertension.
• Subjects with glomerulonephritis or interstitial nephritis or eGFR < 45 ml/min/1.73m2.
• Type I diabetes mellitus.
• Stenotic valvular heart disease for which reduction of blood pressure would be hazardous.
• Subjects with orthostatic hypotension.
• Myocardial infarction, unstable angina, or stroke in the prior 6 months.
• Any medical condition (including psychiatric disease) that would interfere with conducting the study or would not be in the best interest of the subject.
• Inability of the subject to provide informed consent.
• Subjects with sleep apnea.
• Patients taking any drugs that affect blood pressure through off target effects
• Patients with any clinical condition that can affect blood pressure or require the use of drugs that can affect blood pressure. e.g. NSAIDs, steroids, cold remedies.
• Patients who may require any procedure that can affect blood pressure.
• Patients who work a night shift.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Renal Pelvic Denervation; Using the natural orifice of the urethra, the ureters are accessed (bilaterally and in sequence), to allow for an ablation device to be placed into the renal pelvis where RF energy is delivered to ablate renal nerves.	Device: Renal Pelvic Denervation (bilateral); Using the natural orifice of the urethra, the ureters are accessed (bilaterally and in sequence), to allow for an ablation device to be placed into the renal pelvis where RF energy is delivered to ablate renal nerves.; Other Names: renal nerve ablation; renal sympathectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean daytime systolic blood pressure	Mean daytime systolic blood pressure determined from ambulatory blood pressure monitoring	Month 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean 24-hour systolic blood pressure	Mean 24-hour systolic blood pressure determined from ambulatory blood pressure monitoring	Month 2
Change in automated office systolic blood pressure	Automated office blood pressure measured after resting and in triplicate	Month 2
Safety of renal pelvic denervation	Number of subjects with serious adverse events, treatment-emergent adverse events and adverse events assessed, including evidence for acute kidney injury and hypertension-related morbidity	Month 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on renal function	Effects on serum creatinine	Month 2
Effect on index of renal function	Effects on estimated glomerular filtration rate	Month 2
Effects on ABPM at month 6 (durability of effects)	ABPM performed during follow-up	Through month 6
Effects on ABPM month 12 (durability of effects)	ABPM performed during follow-up	Through month 12
Effects on OBM at month 6 (durability of effects)	OBP performed during follow-up	Through month 6
Effects on OBP at month 12 (durability of effects)	OBP performed during follow-up	Through month 12
Safety of renal pelvic denervation	Number of subjects with serious adverse events, treatment-emergent adverse events and adverse events assessed, including evidence of acute kidney injury	Through month 6
Safety of renal pelvic denervation	Number of subjects with serious adverse events, treatment-emergent adverse events and adverse events assessed, including evidence of acute kidney injury	Through month 12

Collaborators and Investigators

• Sponsor: Verve Medical, Inc
• Collaborators: Clinical Accelerator (CRO); Israeli-Georgian Medical Research Clinic Helsicore; Pineo Medical Ecosystem

Publications and helpful links

General Publications

• Hering D, Hubbard BS, Weber MA, Heuser RR. Impact of Renal Pelvic Denervation on Systemic Hemodynamics and Neurohumoral Changes in a Porcine Model. Am J Nephrol. 2021;52(5):429-434. doi: 10.1159/000516186. Epub 2021 May 26.
• Hering D, Nikoleishvili D, Imedadze A, Dughashvili G, Klimiashvili Z, Bekaia E, Shengelia T, Kobalava M, Goguadze O, Emukhvari T, Druker V, Sackner-Bernstein J, Weber MA. Transurethral Renal Pelvic Denervation: A Feasibility Trial in Patients with Uncontrolled Hypertension. Hypertension. 2022 Dec;79(12):2787-2795. doi: 10.1161/HYPERTENSIONAHA.122.20048. Epub 2022 Oct 18.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Actual): February 5, 2022
• Study Completion (Anticipated): December 15, 2022

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 28, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CP0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes