TIVUS Renal Denervation for High Blood Pressure

(THRIVE Trial)

Recruiting at 14 trial locations

Overseen By Jason G Jones, MS, CCRP RAC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: SoniVie Inc.

Must not be taking: Beta blockers, Anticoagulants, Immunosuppressives, NSAIDs

Disqualifiers: Diabetes, Cardiovascular events, Renal issues, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

261 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

Yes, participants will need to stop taking their anti-hypertensive medications for a 4-week period before the procedure and remain off them for 2 months after the procedure.

Is the TIVUS Renal Denervation System safe for humans?

Renal denervation, including systems like TIVUS, has been studied for safety in treating high blood pressure, and research suggests it is generally safe, though its effectiveness varies. Some studies have shown it does not cause significant harm to the renal arteries, but results on its benefits compared to standard treatments are mixed. ^{1 2 3 4 5}

How does the TIVUS Renal Denervation treatment for high blood pressure differ from other treatments?

TIVUS Renal Denervation is a unique treatment for high blood pressure that involves a procedure called renal denervation, which targets the nerves in the kidneys using a catheter-based system. Unlike traditional medications, this treatment uses radiofrequency energy to disrupt nerve activity, potentially reducing blood pressure in patients who do not respond well to standard drug therapies. ^{2 6 7 8 9}

Who Is on the Research Team?

Ajay Kirtane, MD

Principal Investigator

Columbia University

Michel Azizi, MD

Principal Investigator

George Pompidou Hospital

Felix Mahfoud, MD

Principal Investigator

University of Basel

Are You a Good Fit for This Trial?

This trial is for adults aged 22-75 with hypertension, who are on up to two blood pressure medications and willing to stop these meds for a washout period before and after the procedure. They must have controlled BP (<140/90 mmHg), be able to follow study procedures, undergo conscious sedation, and have suitable renal anatomy.

Inclusion Criteria

I have signed and understand the consent form.

I am between 22 and 75 years old.

I have a documented history of high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Wash-out

Participants undergo a 4-week wash-out period off antihypertensive medications before the RDN/Sham procedure

4 weeks

Treatment

Participants receive either the TIVUS™ Renal Denervation System treatment or a sham procedure

1 day

1 visit (in-person)

Post-procedure Monitoring

Participants are monitored off antihypertensive medications for 2 months post-procedure

2 months

Medication Reintroduction

Participants with uncontrolled hypertension are put back on antihypertensive medication according to a medication escalation protocol

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with unblinding at 6 months and potential cross-over for sham subjects

6 months

Long-term Follow-up

All subjects treated with TIVUS are followed for a maximum of 36 months post-procedure

36 months

What Are the Treatments Tested in This Trial?

Interventions

• TIVUS™ Renal Denervation System

Trial Overview The THRIVE study tests the TIVUS Renal Denervation System against a sham (fake) procedure in lowering blood pressure. Participants will stop taking their usual hypertension drugs during the trial to see if this new system can effectively reduce their blood pressure without medication.

How Is the Trial Designed?

Group I: TIVUS™ Renal Denervation System Experimental Treatment 1 Intervention

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

Group II: Sham Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

SoniVie Inc.

Lead Sponsor

Trials

6

Recruited

540+

NAMSA

Collaborator

Trials

55

Recruited

21,500+

European Cardiovascular Research Center

Collaborator

Trials

38

Recruited

48,500+

Published Research Related to This Trial

In a study of 46 patients with drug-resistant hypertension, the multi-electrode ablation system for renal denervation led to significant reductions in blood pressure over 24 months, with office BP decreasing by an average of -29/-13 mmHg.

The procedure was found to be safe, with no new serious device or procedure-related adverse events reported, indicating that renal denervation can be a reliable treatment option for patients with difficult-to-treat hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN I first-in-human study using a multi-electrode ablation system. Tsioufis, CP., Papademetriou, V., Dimitriadis, KS., et al.[2022]

Early trials of renal denervation showed significant reductions in blood pressure, suggesting a potential benefit for treating hypertension.

However, later studies comparing renal denervation to sham procedures yielded neutral results, indicating that current evidence is insufficient to establish it as a standard clinical therapy for hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rise, fall, and possible resurrection of renal denervation. Gulati, R., Raphael, CE., Negoita, M., et al.[2018]

The Vessix Renal Denervation System significantly reduced office blood pressure by an average of 24.7 mmHg and ambulatory blood pressure by 8.4 mmHg after six months in patients with resistant hypertension, demonstrating its efficacy.

The procedure showed a favorable safety profile, with no serious renal artery injuries or significant changes in renal function, as indicated by stable eGFR levels, although one case of renal artery stenosis required stenting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal denervation with a percutaneous bipolar radiofrequency balloon catheter in patients with resistant hypertension: 6-month results from the REDUCE-HTN clinical study. Sievert, H., Schofer, J., Ormiston, J., et al.[2022]

Renal denervation therapy (RDN) has been found to be safe for patients with resistant hypertension, but its effectiveness in lowering blood pressure is variable and not significantly better than standard medical therapy.

Recent studies and ongoing trials are focusing on improving the procedural aspects of RDN and identifying patients who truly have treatment-resistant hypertension, which may help uncover potential benefits of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status of Renal Denervation in Hypertension. Briasoulis, A., Bakris, GL.[2018]

In a review of 50 trials involving 5,769 subjects, the rate of renal artery adverse events following renal denervation was found to be very low, with only 0.45% of patients experiencing renal artery stenosis or dissection.

The annual incidence rate of stent implantation after renal denervation was just 0.20%, indicating that serious complications are rare, and most adverse events occurred within the first year after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review and meta-analysis of renal artery damage following percutaneous renal denervation with radiofrequency renal artery ablation. Townsend, RR., Walton, A., Hettrick, DA., et al.[2021]

The DENEX™ renal sympathetic denervation system demonstrated a favorable safety profile in a pilot study involving 16 patients with resistant hypertension, with no major adverse events reported during the 6-month follow-up.

Patients experienced a significant reduction in office systolic blood pressure (SBP) from 164.6 mmHg to 142.0 mmHg after 3 months, indicating the efficacy of the DENEX™ system in managing resistant hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-label, Single-arm, Multicenter Feasibility Study Evaluating the Safety of Catheter-based Renal Denervation with DENEX™ in Patients with Uncontrolled Hypertension on Standard Medical Therapy. Kim, CJ., Chang, K., Kim, BK., et al.[2021]

The second generation EnligHTN Renal Denervation System safely reduced office blood pressure in patients with drug-resistant hypertension, showing significant decreases at multiple time points up to 24 months after the procedure.

No serious adverse events related to the device or procedure were reported, indicating a favorable safety profile for this treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension. Worthley, SG., Wilkins, GT., Webster, MW., et al.[2022]

Renal denervation is a promising device-based procedure for treating hypertension, showing safety and efficacy in recent clinical trials with new-generation devices, although its clinical use remains debated.

The Italian Society of Arterial Hypertension recommends careful patient selection for renal denervation, considering factors like blood pressure, cardiovascular risk, medication adherence, and patient preferences, while emphasizing the need for further studies to validate these recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian Society of Arterial Hypertension (SIIA) Position Paper on the Role of Renal Denervation in the Management of the Difficult-to-Treat Hypertensive Patient. Bruno, RM., Taddei, S., Borghi, C., et al.[2020]

Renal denervation (RDN) significantly reduced renal vascular resistance in patients with drug-resistant hypertension and type 2 diabetes, particularly in those with elevated baseline renal resistive index (RRI ≥ 0.7).

While RDN did not significantly change estimated glomerular filtration rate (eGFR), it effectively lowered blood pressure by an average of -10.9 mmHg systolic and -5.5 mmHg diastolic after 12 months, indicating its potential as a treatment option for managing hypertension in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Favorable effect of renal denervation on elevated renal vascular resistance in patients with resistant hypertension and type 2 diabetes mellitus. Manukyan, M., Falkovskaya, A., Mordovin, V., et al.[2023]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN I first-in-human study using a multi-electrode ablation system. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The rise, fall, and possible resurrection of renal denervation. [2018]

3. France pubmed.ncbi.nlm.nih.gov

Renal denervation with a percutaneous bipolar radiofrequency balloon catheter in patients with resistant hypertension: 6-month results from the REDUCE-HTN clinical study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Current Status of Renal Denervation in Hypertension. [2018]

5. France pubmed.ncbi.nlm.nih.gov

Review and meta-analysis of renal artery damage following percutaneous renal denervation with radiofrequency renal artery ablation. [2021]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

An Open-label, Single-arm, Multicenter Feasibility Study Evaluating the Safety of Catheter-based Renal Denervation with DENEX™ in Patients with Uncontrolled Hypertension on Standard Medical Therapy. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Italian Society of Arterial Hypertension (SIIA) Position Paper on the Role of Renal Denervation in the Management of the Difficult-to-Treat Hypertensive Patient. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Favorable effect of renal denervation on elevated renal vascular resistance in patients with resistant hypertension and type 2 diabetes mellitus. [2023]