Therapeutic Intravascular Ultrasound (TIVUS) Renal Denervation System for the Adjunctive Treatment of Hypertension

What is the Purpose of this Study?

The purpose of this study is to evaluate the safety and effectiveness of an experimental device called the TIVUS System to treat people who have hypertension (high blood pressure) that is not controlled despite treatment with blood pressure medications. Individuals with controlled blood pressure who are willing to come off their blood pressure medications for the purpose of being in this study may also participate. The study aims to determine whether the device, which uses sound waves (ultrasonic energy) to heat up and impair some of the nerves around the arteries leading to the kidneys, will control blood pressure as well as or better than using medication. The information collected from this study will be used to evaluate how well participants do when treated with the TIVUS system both immediately after treatment and over a longer period of time (3 years). Procedures include angiograms, ultrasounds, blood and urine collection, and a possible procedure in which an ultrasound catheter is placed in the kidney’s main artery to deliver a short pulse of heat. Participants will be randomly assigned to either the treatment group using the TIVUS system or to the sham group (no treatment). For every 2 patients treated with TIVUS system, 1 will be assigned to the sham group; participants will have approximately a 67% chance of receiving treatment with the TIVUS system. Blood pressure-lowering medications will eventually be restarted during the study, and participants who received the sham procedure may have the chance to receive renal denervation with the TIVUS system after approximately 6 months of study participation.

Eligibility

1. Appropriately signed and dated informed consent
2. Male and female adults with age between ≥22 and ≤75 years at time of consent
3. Documented history of hypertension
4. Previously or currently prescribed antihypertensive therapy

Inclusion Criteria:

1. Appropriately signed and dated informed consent
2. Male and female adults with age between ≥22 and ≤75 years at time of consent
3. Documented history of hypertension
4. Previously or currently prescribed antihypertensive therapy
5. Subject has an office BP (average of 3 seated measurements) of:
1. Uncontrolled BP: ≥ 140/90 mmHg \<180/110 mmHg at Screening Visit (V0) while stable for at least 4 weeks on 0-2 anti-hypertensive medications of different classes\* and willing to stop anti-hypertensive medication(s) for 4 weeks wash-out and 2-months post-procedure, (subjects with a history of treatment with anti-hypertensive medications but are not currently taking any at screening will undergo a 4-week run-in period) or,
2. Controlled BP: \< 140/90 mmHg while stable for at least 4 weeks on 1-2 antihypertensive medications of different classes and willing to stop anti-hypertensive medication(s) for 4 weeks wash-out and 2-months post-procedure
6. Able and willing to comply with all study procedures
7. Subject is willing to have and is a good candidate for conscious sedation
Subjects who meet the following criteria will be considered eligible for randomization:
* Documented daytime systolic ABP ≥ 135 mmHg and \< 180 mmHg after 4-week washout/run-in period.\*\*
* Suitable renal anatomy compatible with the renal denervation procedure, documented by renal CTA or MRA of good quality performed within one year prior to consent (a CTA or MRA will be obtained in subjects without a recent (≤1 year) cross-sectional renal imaging). The renal angiogram procedure done in the cath lab prior to randomization will serve as the final anatomy compatibility check.
* Potassium-sparing diuretics such as Amiloride hydrochloride and Triamterene may be prescribed in combination with another diuretic (e.g. a thiazide or loop diuretic) for their potassium conservation properties. In this situation, the diuretic combination is considered as a single class of anti-hypertensive.

Exclusion Criteria:

2. Uncorrected causes of secondary hypertension other than sleep apnea (including, but not limited to): aldosteronism, renal parenchymal disease, renovascular disease, excess catecholamines, Cushing's syndrome, erythropoietin use, pheochromocytoma, hypo/hyperthyroidism, hyperparathyroidism, acromegaly)
3. Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma HbA1c ≥ 9.0%)
4. eGFR of \<40 mL/min/1.73 m2 CKD-EPI as calculated using the CKD-EPI 2021 equation
5. Cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident) within 6 months prior to consent
6. History of severe cardiovascular event (e.g. myocardial infarction, unstable angina, CABG, acute heart failure requiring hospitalization (NYHA III-IV) within 12 months prior to consent
7. Subject has severe valvular stenosis or insufficiency
8. Documented repeat (\>1) hospitalization for hypertensive crisis within the prior 12 months and/or any hospitalization for hypertensive crisis within three (3) months prior to consent
9. Prescribed to any standard antihypertensive cardiovascular medication (e.g. beta blockers) for other chronic conditions (e.g. ischemic heart disease) such that discontinuation might pose serious risk to health in the opinion of the investigator
10. Subject with rapid, uncontrolled, symptomatic atrial fibrillation
11. Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; baroreflex stimulator)
12. Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea.
13. Subject has a planned major surgery (any procedure requiring general anesthesia) in the next 12 months.
14. Subject on anticoagulant therapy that cannot be temporarily withheld for study procedure.
15. Primary pulmonary hypertension
16. Documented contraindication or allergy to contrast medium not amenable to treatment
17. Limited life expectancy of \< 1 year at the discretion of the Investigator
18. Night shift worker
19. Subject has frequent intermittent or chronic pain that results in treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for two or more days per week over the month prior to enrollment.
20. Subject is taking immunosuppressive therapy for diseases featuring vasculitis
21. Any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements or whose participation may result in data analysis confounders
22. Pregnant, nursing or planning to become pregnant within 12 months post procedure.
Negative pregnancy test required, documented within a maximum of 7 days prior to procedure for all women of childbearing potential. Documentation of effective contraception is also required for women of childbearing potential
23. Subject has a planned major surgery or cardiovascular intervention in the next 6 months
24. Subject with history of renal transplantation
25. Evidence of active infection within 7 days of procedure (based on positive lab test and requiring therapy).
26. Subject has hypertrophic cardiomyopathy or amyloidosis.
27. Prior renal denervation procedure
28. Concurrent enrollment in any other investigational drug or device trial (participation in non-interventional studies/registries is acceptable)
29. Subject on a beta blocker for a condition other than antihypertension
The following characteristics identified either on the renal artery CT scan or MRI or on the Eligibility II Renal artery Angiogram will prevent the subject from being included:
1. Main renal arteries lumen diameter \< 4 mm.
2. Main renal treatable artery length \<20mm (may include proximal branching).
3. Accessory renal arteries that supplies ≥ 25% of the parenchyma, and \< 4 mm in lumen diameter.
4. Aorto-renal angle that prevents a safe cannulation of the renal artery.
5. Severe common femoral artery, common and/or external iliac artery, renal, iliac or aortic calcification or tortuosity that may compromise the safe performance and completion of the TIVUS™ procedure.
6. Hemodynamically or anatomically significant renal artery abnormality or stenosis in either renal artery which, would interfere with safe cannulation of the renal artery or meets local standards for surgical repair or interventional dilation (NOTE: vessel areas with calcification and fibromuscular dysplasia (FMD) should be avoided as intended treatment areas).
7. Any renal artery stenosis \> 30% by visual assessment.
8. Any renal artery aneurysm (\>50% of the main renal artery reference vessel diameter by visual estimate).
9. Presence of fibromuscular dysplasia of the renal arteries
10. Significant renal artery atheroma, aneurysm, calcification in the target vessel identified on CT Angiogram

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A Pivotal, Prospective, Multicenter, 2:1 Randomized, Double Blind, Controlled, Study Comparing the Therapeutic Intravascular Ultrasound Renal Denervation System vs. Sham for the Adjunctive Treatment of Hypertension .

Study Details

Disease Type/Condition

Hypertension

Principal Investigator

Rader, Florian

Age Group

Adult

Phase

N/A

IRB Number

STUDY00003691

ClinicalTrials.gov ID

NCT06559891

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org