Renal Denervation for High Blood Pressure

(REDUCED Trial)

Recruiting at 8 trial locations

Overseen By Ajay Kirtane, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: SoniVie Inc.

Must be taking: Antihypertensives

Must not be taking: NSAIDs, Immunosuppressives, Anticoagulants

Disqualifiers: Renal abnormalities, Diabetes, Heart disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, multicenter, non-randomized, open-label clinical study of the safety and performance of the TIVUS™ System in subjects with uncontrolled stage 2 hypertension in order to assess the safety and effectiveness of the TIVUS™ System when used for renal artery denervation. The study will assess the acute and chronic safety of the procedure as well as the reduction in 24-hour ambulatory mean systolic blood pressure from baseline to 3 months after the procedure.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial requires that you maintain your anti-hypertensive medication regimen for at least 3 months.

What data supports the effectiveness of the TIVUS™ System treatment for high blood pressure?

Research on renal denervation, a treatment that uses energy to disrupt nerves in the kidneys, shows it can lower blood pressure in patients with resistant hypertension (high blood pressure that doesn't respond to medication). Studies like the DENERHTN trial and others have confirmed its effectiveness when combined with other treatments. ^{1 2 3 4 5}

Is renal denervation safe for humans?

Studies on renal denervation, including those using different systems like radiofrequency and balloon catheters, have been conducted to assess safety. While some trials report limited long-term safety data, others focus on evaluating adverse events related to the procedure, indicating ongoing research to ensure its safety in humans. ^{2 6 7 8 9}

How does the TIVUS™ System treatment for high blood pressure differ from other treatments?

The TIVUS™ System is unique because it uses ultrasound energy to target the renal nerves, which may help lower blood pressure by disrupting nerve signals that contribute to hypertension. This approach is different from traditional drug therapies and other renal denervation systems that typically use radiofrequency energy. ^{3 6 10 11 12}

Research Team

Ajay Kirtane, MD

Principal Investigator

Columbia University/NYPH

Eligibility Criteria

This trial is for adults aged 18-80 with stage 2 hypertension, who have high blood pressure despite taking medication. Participants should be willing to maintain their current medication regimen and comply with study procedures. Pregnant women, individuals planning major surgeries, those on certain anticoagulants or with severe kidney issues are excluded.

Inclusion Criteria

Patient is able and willing to comply with all study procedures.

Written informed consent to participate in the study obtained from the patient, according to local regulations, prior to initiation of any study mandated procedure

My average daytime blood pressure is between 135 and 179 mm Hg after a month of monitoring.

Exclusion Criteria

I have not had an infection in the week before my procedure.

I have a heart valve problem that could worsen with sudden blood pressure drops.

I have not had major surgery or heart-related procedures in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo renal denervation using the TIVUS™ System

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Multiple visits (in-person and virtual)

Long-term Follow-up

Participants are monitored for changes in blood pressure and renal function

36 months

Treatment Details

Interventions

• TIVUS™ System

Trial Overview The REDUCED 1 trial tests the TIVUS™ System's safety and effectiveness in lowering blood pressure through renal denervation—a procedure that disrupts nerve signals contributing to high blood pressure. The focus is on changes in daytime systolic blood pressure after three months.

Participant Groups

Group I: Renal denervation Experimental Treatment 1 Intervention

Denervating the sympathetic nerves surrounding the renal vasculature using unfocused ultrasound

Who Is Running the Clinical Trial?

SoniVie Inc.

Lead Sponsor

Trials

6

Recruited

540+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

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

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial. [2017]

2. 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]

3. 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]

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

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial. [2023]

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

Current Status of Renal Denervation in Hypertension. [2018]

6. England pubmed.ncbi.nlm.nih.gov

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

7. 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]

8. France pubmed.ncbi.nlm.nih.gov

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

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

Safety and Efficacy of a New Renal Denervation Catheter in Hypertensive Patients in the Absent of Antihypertensive Medications: A Pilot Study. [2022]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Paradise™ Ultrasound Renal Denervation System for the treatment of hypertension. [2022]

12. 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]