Pulmonary Artery Denervation for Pulmonary Hypertension

(TROPHY-II Trial)

Not currently recruiting at 2 trial locations

Overseen By Dalit Shav, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: SoniVie Inc.

Must be taking: Guideline therapy

Disqualifiers: Pregnancy, Life expectancy <1 year, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called the TIVUS™ System, a device for pulmonary artery denervation, to determine its safety and effectiveness for people with pulmonary hypertension caused by left heart disease. The study will measure changes in heart function, exercise ability, and quality of life. It is open to individuals with pulmonary hypertension who have heart failure and are on stable medication. As an unphased trial, this study provides an opportunity to contribute to groundbreaking research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should be on stable guideline-directed medical therapy for their condition.

What prior data suggests that the TIVUS™ System is safe for pulmonary artery denervation?

Studies have shown that the TIVUS™ System is generally safe for patients. In one study, researchers checked for any procedure-related problems within 30 days, and most patients did not experience significant issues. Another report highlighted the system's safety and effectiveness in treating pulmonary arterial hypertension. While these findings are promising, it is important to remember that the TIVUS™ System remains under investigation, and further research will help confirm its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for pulmonary hypertension, which typically involves medications like vasodilators, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors, the TIVUS™ System offers a novel approach by using targeted ultrasound technology to perform pulmonary artery denervation. This technique aims to reduce the sympathetic nerve activity that contributes to high blood pressure in the lungs. Researchers are excited because this method has the potential to provide long-lasting relief without the need for daily medication, offering a new avenue for patients who may not respond well to current drug therapies.

What evidence suggests that the TIVUS™ System is effective for pulmonary hypertension?

Research has shown that the TIVUS™ System, a treatment for high blood pressure in the lungs, looks promising. It safely reduces the activity of certain nerves in the pulmonary artery, helping to lower lung blood pressure. One study found that after 12 months, 58% of patients experienced better heart and lung function, improved exercise ability, and overall well-being. This suggests that the TIVUS™ System may effectively improve symptoms and quality of life for people with pulmonary hypertension caused by left heart disease. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with pulmonary hypertension due to left heart disease, who are in a stable condition on standard medical therapy. They must have specific types of pulmonary hypertension confirmed by tests and be able to give informed consent. People with life-threatening conditions, certain heart devices or anatomy issues, pregnant women, or those in other drug/device trials can't join.

Inclusion Criteria

My pulmonary hypertension was confirmed by a special heart and lung test.

I have moderate heart condition symptoms.

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

Exclusion Criteria

I have a significant narrowing in my lung arteries.

You are expected to live for less than a year.

Patient with significant co-morbid condition(s) which, at the discretion of the PI, are deemed to prohibit study entry

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo pulmonary artery denervation using the TIVUS™ System

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits (in-person and virtual)

Long-term follow-up

Monitoring of adverse events and changes in clinical parameters

12 months

What Are the Treatments Tested in This Trial?

Interventions

• TIVUS™ System

Trial Overview The TIVUS™ System's safety and effectiveness for treating group II pulmonary hypertension are being tested. This non-randomized study will enroll up to 15 patients across up to three centers. It aims to improve clinical parameters like hemodynamics, exercise tolerance, and quality of life.

Who Is Running the Clinical Trial?

SoniVie Inc.

Lead Sponsor

Trials

6

Recruited

540+

Published Research Related to This Trial

A review of 588 pediatric adverse event reports related to pulmonary hypertension medications revealed significant safety concerns, including 27 adverse events not previously documented in the literature, such as pulmonary hemorrhage and pneumonia.

The findings highlight the need for better communication of postmarket adverse event data from the FDA to healthcare providers, as many medications for pediatric pulmonary hypertension are used off-label and may carry risks that are not well understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients. Maxey, DM., Ivy, DD., Ogawa, MT., et al.[2021]

Pulmonary artery denervation is a promising new treatment for pulmonary arterial hypertension that aims to reduce sympathetic activity in the pulmonary circulation, showing safety and some positive effects in initial studies.

Despite its potential, the use of pulmonary artery denervation is currently limited due to the lack of large-scale, well-designed randomized controlled trials to fully establish its efficacy and scope in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary artery denervation for pulmonary arterial hypertension. Constantine, A., Dimopoulos, K.[2021]

Pulmonary artery denervation (PADN) significantly reduces mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) while improving cardiac output (CO) and exercise capacity (measured by 6-minute walk distance) in patients with pulmonary hypertension, based on a meta-analysis of 8 studies involving 213 patients.

The treatment also leads to a significant decrease in the proportion of patients with severe cardiac function (NYHA class III and IV), indicating an improvement in overall quality of life for those with pulmonary hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis of Pulmonary Artery Denervation for Treatment of Pulmonary Hypertension. Zuo, W., Liu, N., Xiao, Y., et al.[2022]

In a study of 240 patients with pulmonary vein stenosis who underwent 841 catheterizations, serious adverse events occurred in 12% of cases, with pulmonary hemorrhage and arrhythmia being the most common, while severe events like stroke and death were rare.

Younger patients (under 6 months) and those with low oxygen saturation or severely elevated pulmonary artery pressure were more likely to experience serious adverse events and require high-level cardiorespiratory support after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Serious Adverse Events and High-Level Cardiorespiratory Support in Patients Undergoing Transcatheter Pulmonary Vein Interventions. Barreto, JA., Gauvreau, K., Porras, D., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1936879819326329

Intravascular Ultrasound Pulmonary Artery Denervation to ... The aim of this study was to investigate whether therapeutic intravascular ultrasound pulmonary artery denervation (PDN) is safe and reduces pulmonary vascular ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32327095/

Intravascular Ultrasound Pulmonary Artery Denervation to ... The aim of this study was to investigate whether therapeutic intravascular ultrasound pulmonary artery denervation (PDN) is safe and reduces pulmonary vascular ...

3. eurointervention.pcronline.com eurointervention.pcronline.com/article/pulmonary-artery-denervation-using-catheter-based-ultrasonic-energy

Pulmonary artery denervation using catheter-based ... Ultrasound PDN is safe and effective in the preclinical setting, with energy delivery to a depth that would permit targeting sympathetic nerves in humans.

4. clinicaltrial.be clinicaltrial.be/en/details/10025?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

TReatment Of Pulmonary HYpertension 1-US Study The objective of this study is to assess the safety, performance and initial effectiveness of the TIVUS™ System when used for pulmonary ...

5. atsjournals.org atsjournals.org/doi/pdf/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A7278?download=true

Percutaneous Endovascular Ultrasound Pulmonary Artery ... At 12- months a combined assessment of hemodynamics, functional capacity and clinical risk score was improved in 58% (11), maintained in 32% (6) and declined in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06559891

Study Details | NCT06559891 | THRIVE- THerapeutic ... The primary objective of the THRIVE Pivotal study is to demonstrate the adjunctive effectiveness and the safety of the TIVUS system in:.

7. techwald.com techwald.com/sonivie-presents-clinical-trial-data-supporting-the-safety-and-efficacy-of-the-tivus-system-in-the-treatment-of-pulmonary-arterial-hypertension/

SoniVie Presents Clinical Trial Data Supporting the Safety ... SoniVie Presents Clinical Trial Data Supporting the Safety and Efficacy of the TIVUS™ System in the Treatment of Pulmonary Arterial Hypertension.

8. evtoday.com evtoday.com/news/sonivie-gains-ide-approval-for-thrive-pivotal-trial-of-tivus-rdn-system

SoniVie Gains IDE Approval for THRIVE Pivotal Trial of ... SoniVie announced that the FDA recently approved an investigational device exemption for the THRIVE pivotal study of the company's Tivus therapeutic ...