THRIVE- THerapeutic IntravasculaR Ultrasound (TIVUS™) REnal Denervation System Versus Sham for the Adjunctive Treatment of Hypertension

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:

6. Uncontrolled BP: ≥ 140/90 mmHg <180/110 mmHg at Screening Visit (V0) whilestable for at least 4 weeks on 0-2 anti-hypertensive medications of differentclasses* and willing to stop anti-hypertensive medication(s) for 4 weekswash-out and 2-months post-procedure, (subjects with a history of treatmentwith anti-hypertensive medications but are not currently taking any atscreening will undergo a 4-week run-in period) or,

7. Controlled BP: < 140/90 mmHg while stable for at least 4 weeks on 1-2antihypertensive medications of different classes and willing to stopanti-hypertensive medication(s) for 4 weeks wash-out and 2-monthspost-procedure

8. Able and willing to comply with all study procedures

9. 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-weekwashout/run-in period.**

• Suitable renal anatomy compatible with the renal denervation procedure, documentedby renal CTA or MRA of good quality performed within one year prior to consent (aCTA or MRA will be obtained in subjects without a recent (≤1 year) cross-sectionalrenal imaging). The renal angiogram procedure done in the cath lab prior torandomization will serve as the final anatomy compatibility check.

• Potassium-sparing diuretics such as Amiloride hydrochloride and Triamterene maybe prescribed in combination with another diuretic (e.g. a thiazide or loopdiuretic) for their potassium conservation properties. In this situation, thediuretic combination is considered as a single class of anti-hypertensive.

Exclusion Criteria:

1. Subject has been previously diagnosed with abnormal renal artery anatomy and/orrenal anatomy such as a single kidney, ectopic or horseshoe kidney, polycystickidney disease, kidney tumors or other findings precluding renal denervation therapyas detailed in the angiographic exclusion criteria

2. Uncorrected causes of secondary hypertension other than sleep apnea (including, butnot 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, cerebrovascularaccident) 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 monthsprior to consent

7. Subject has severe valvular stenosis or insufficiency

8. Documented repeat (>1) hospitalization for hypertensive crisis within the prior 12months and/or any hospitalization for hypertensive crisis within three (3) monthsprior to consent

9. Prescribed to any standard antihypertensive cardiovascular medication (e.g. betablockers) for other chronic conditions (e.g. ischemic heart disease) such thatdiscontinuation 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/spinalstimulator; baroreflex stimulator)

12. Chronic oxygen support or mechanical ventilation other than nocturnal respiratorysupport for sleep apnea.

13. Subject has a planned major surgery (any procedure requiring general anesthesia) inthe next 12 months.

14. Subject on anticoagulant therapy that cannot be temporarily withheld for studyprocedure.

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 withnonsteroidal anti-inflammatory drugs (NSAIDs) for two or more days per week over themonth 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 abilityto comprehend or follow instructions, or for any reason in the opinion of theinvestigator, would be unlikely or unable to comply with study protocol requirementsor 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 toprocedure for all women of childbearing potential. Documentation of effectivecontraception is also required for women of childbearing potential

23. Subject has a planned major surgery or cardiovascular intervention in the next 6months

24. Subject with history of renal transplantation

25. Evidence of active infection within 7 days of procedure (based on positive lab testand 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

Angiographic Exclusion Criteria:

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 lumendiameter.

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 oraortic calcification or tortuosity that may compromise the safe performance andcompletion of the TIVUS™ procedure.

6. Hemodynamically or anatomically significant renal artery abnormality or stenosis ineither renal artery which, would interfere with safe cannulation of the renal arteryor meets local standards for surgical repair or interventional dilation (NOTE:vessel areas with calcification and fibromuscular dysplasia (FMD) should be avoidedas 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 diameterby visual estimate).

9. Presence of fibromuscular dysplasia of the renal arteries

10. Significant renal artery atheroma, aneurysm, calcification in the target vesselidentified on CT Angiogram