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

NCT ID: NCT06559891

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

261 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-03

Study Completion Date

2028-08-15

Brief Summary

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The primary objective of the THRIVE Pivotal study is to demonstrate the adjunctive effectiveness and the safety of the TIVUS system in:

1. subjects with hypertension (HTN) receiving up to 2 anti-hypertensive drugs of different classes in whom the anti-hypertensive medications will be stopped for a 4-week wash-out period before RDN/Sham procedure and during 2 months after procedure.
2. subjects with controlled hypertension receiving up to 2 anti-hypertensive drugs of different classes and who accept to be off-medications for a 4-week wash-out period before RDN/Sham procedure and 2 months after the procedure

Detailed Description

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THRIVE is an international, multicenter, randomized, double blind, sham-controlled study, designed to demonstrate the adjunctive effectiveness and safety of the TIVUS System in hypertensive subjects while subjects are maintained off-antihypertensive medications for a 4-week wash-out period before RDN/Sham procedure and 2 months after procedure. At two months after procedure, subjects with uncontrolled hypertension are put back on antihypertensive medication according to a medication escalation protocol. Unblinding will be performed at 6 months. Uncontrolled sham subjects can cross-over to RDN procedure at 6-months. The sham procedure will be minimally invasive to reduce risk to subjects. All subjects treated with TIVUS will be followed for a maximum of 36 months post procedure.

Conditions

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Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

2:1 randomization will be used to assign subjects to treatment (RDN) or control (sham). Randomization will occur immediately after the renal angiogram.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
The subjects and all study personnel taking follow-up blood pressure measurements will be blinded to the randomization up to 6 months post-randomization. Subjects will complete a blinding assessment prior to hospital discharge, at 2M and 6M FU. Study unblinding will occur at 6-months FU.

ABPM measurements will be sent to an independent core lab for data cleaning and analysis and will be blinded to the randomization assignment.

Study Groups

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TIVUS™ Renal Denervation System

Following angiogram, subjects found anatomically eligible and randomized to the renal denervation arm will be treated with the TIVUS™ Renal Denervation System.

Group Type EXPERIMENTAL

TIVUS™ Renal Denervation System

Intervention Type DEVICE

Renal artery catheterization procedure used to denervate the renal sympathetic nerves in the perivascular space using ultrasound energy.

Sham

For those subjects randomized to the sham control, the angiogram will serve as the sham procedure.

Group Type SHAM_COMPARATOR

Sham

Intervention Type OTHER

For those subjects randomized to the sham control, the angiogram will serve as the sham procedure.

Interventions

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TIVUS™ Renal Denervation System

Renal artery catheterization procedure used to denervate the renal sympathetic nerves in the perivascular space using ultrasound energy.

Intervention Type DEVICE

Sham

For those subjects randomized to the sham control, the angiogram will serve as the sham procedure.

Intervention Type OTHER

Other Intervention Names

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Renal Denervation

Eligibility Criteria

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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
Minimum Eligible Age

22 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NAMSA

OTHER

Sponsor Role collaborator

European Cardiovascular Research Center

NETWORK

Sponsor Role collaborator

SoniVie Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ajay Kirtane, MD

Role: STUDY_CHAIR

Columbia University

Michel Azizi, MD

Role: STUDY_CHAIR

George Pompidou Hospital

Felix Mahfoud, MD

Role: STUDY_CHAIR

University of Basel

Locations

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Cardiology, PC

Birmingham, Alabama, United States

Site Status RECRUITING

Honor Health Research Institue

Scottsdale, Arizona, United States

Site Status RECRUITING

St. Bernard's Medical Center

Jonesboro, Arkansas, United States

Site Status RECRUITING

Arkansas Heart Hospital

Little Rock, Arkansas, United States

Site Status RECRUITING

Cedar-Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Stanford University

Stanford, California, United States

Site Status RECRUITING

Bridgeport

Bridgeport, Connecticut, United States

Site Status RECRUITING

University of South Florida

Tampa, Florida, United States

Site Status RECRUITING

Ascension Alexian Brothers

Elk Grove Village, Illinois, United States

Site Status RECRUITING

St. John's Prairie Heart

Springfield, Illinois, United States

Site Status RECRUITING

Southern Illinois University, School of Medicine

Springfield, Illinois, United States

Site Status RECRUITING

Cardiovascular Institute of the South

Houma, Louisiana, United States

Site Status RECRUITING

Ochsner Medical Center

New Orleans, Louisiana, United States

Site Status RECRUITING

Gulfport Memorial Hospital

Gulfport, Mississippi, United States

Site Status RECRUITING

Jackson Heart

Jackson, Mississippi, United States

Site Status RECRUITING

St. Luke's Hospital

Kansas City, Missouri, United States

Site Status RECRUITING

Renown Regional Medical Center

Reno, Nevada, United States

Site Status RECRUITING

Virtua Health

Camden, New Jersey, United States

Site Status RECRUITING

Nyph/Cumc

New York, New York, United States

Site Status NOT_YET_RECRUITING

NC Heart and Vascular

Raleigh, North Carolina, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Medical City

Fort Worth, Texas, United States

Site Status RECRUITING

Houston Medical Center

Houston, Texas, United States

Site Status RECRUITING

St Marks Hospital

Salt Lake City, Utah, United States

Site Status RECRUITING

Chippenham Hospital

Richmond, Virginia, United States

Site Status RECRUITING

Hopital Saint André

Bordeaux, , France

Site Status RECRUITING

Hôpital Européen Georges-Pompidou

Paris, , France

Site Status RECRUITING

Universitätsklinikum Erlangen

Erlangen, , Germany

Site Status RECRUITING

Frankfurt Sankt Katharinen Krankenhaus

Frankfurt, , Germany

Site Status RECRUITING

Freiburg Herzzenrtum

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Marienkrankenhaus Hamburg

Hamburg, , Germany

Site Status RECRUITING

Herne Marien Hospital

Herne, , Germany

Site Status RECRUITING

Herzzentrum Leipzig

Leipzig, , Germany

Site Status RECRUITING

Sana Kliniken Lubeck

Lübeck, , Germany

Site Status RECRUITING

Athens Hippokration

Athens, , Greece

Site Status RECRUITING

University of Crete

Heraklion, , Greece

Site Status RECRUITING

Thessaloniki Hippokration General Hospital

Thessaloniki, , Greece

Site Status RECRUITING

Clinica Montevergine

Mercogliano, , Italy

Site Status RECRUITING

Ospedale Sant'Andrea

Roma, , Italy

Site Status RECRUITING

Countries

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United States France Germany Greece Italy

Central Contacts

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Janelle Noble

Role: CONTACT

Phone: 612-598-4368

Email: [email protected]

Facility Contacts

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Susan DeRamus

Role: primary

Taral Patel, MD

Role: primary

Maximilliano Arroyo, MD

Role: primary

Sasha Potter

Role: backup

Andre Paixao, MD

Role: primary

Leybi Ramirez-Kelly, PhD

Role: backup

Florian Radar, M.D.

Role: primary

Maria Thottam

Role: backup

David Lee, MD

Role: primary

Florian Rader, MD

Role: primary

Fadi Mater, MD

Role: primary

Avinash Murthy, MD

Role: primary

John Flack, MD

Role: primary

Craig Walker

Role: primary

James Jenkins, MD

Role: primary

Wayne Latack, MD

Role: primary

Grey Bennett, MD

Role: primary

Steven Laster, MD

Role: primary

Michael Bloch, MD

Role: primary

Kintur Sanghvi, MD

Role: primary

Ajay Kirtane, MD

Role: primary

Suzanne Edwards, PhD

Role: backup

James Pierre-Louis

Role: primary

Deborah Cohen, MD

Role: primary

Farhan Ali, M.D.

Role: primary

Arnav Kumar, M.D.

Role: primary

Vamsee Yaganti, M.D.

Role: primary

Nayef Abouzaki, MD

Role: primary

Antoine Cremer, MD

Role: primary

Michel Azizi, MD, PhD

Role: primary

Roland Schmieder, MD, PhD

Role: primary

Horst Sievert, MD

Role: primary

Elias Noory, MD

Role: primary

Jury Schewel, MD

Role: primary

Christian Ukena, MD, PhD

Role: primary

Karl Fengler, MD

Role: primary

Joachim Weil, MD

Role: primary

K Tsioufis, MD, PhD

Role: primary

Maria Marketou, MD, PhD

Role: primary

Michalis Doumas, MD

Role: primary

Luigi Salemme, MD

Role: primary

Emanuele Barbato, MD, PhD

Role: primary

Other Identifiers

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CLNS07-001

Identifier Type: -

Identifier Source: org_study_id