Pulmonary Artery Denervation for Pulmonary Hypertension

(TROPHY-II Trial)

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

15 Participants Needed

Trial Summary

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 data supports the effectiveness of the TIVUS™ System treatment for pulmonary hypertension?

Research shows that pulmonary artery denervation, like the TIVUS™ System, can safely reduce pulmonary artery pressure and improve quality of life in patients with pulmonary hypertension. Initial studies have shown positive effects on disease markers, although more large-scale trials are needed to confirm these findings. ^{1 2 3 4 5}

Is pulmonary artery denervation safe for humans?

Initial clinical trials and pre-clinical studies suggest that pulmonary artery denervation, including the TIVUS™ System, can be performed safely in humans with some positive effects on health markers. However, more large-scale studies are needed to confirm its safety. ^{2 4 6 7 8}

How is the TIVUS™ System treatment different from other treatments for pulmonary hypertension?

The TIVUS™ System is unique because it uses intravascular ultrasound to perform pulmonary artery denervation, which aims to reduce the activity of the sympathetic nervous system in the lungs, potentially lowering blood pressure in the pulmonary arteries. This approach is different from standard drug therapies as it is a procedural intervention rather than a medication. ^{1 2 3 4 9}

What is the purpose of this trial?

The objective of this study is to assess the safety and initial effectiveness of the TIVUS™ System when used for pulmonary artery denervation in group II PH patients through change in clinical parameters including hemodynamics, exercise tolerance, and quality of life. This is a prospective, multi-center, non-randomized, open-label clinical trail. The study will be conducted in up to 3 centers and will recruit up to 15 patients diagnosed with pulmonary hypertension due to left heart disease that demonstrate combined pre and post capillary involvement with PVR\>3 wood units.

Eligibility Criteria

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

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

Treatment Details

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+

Findings from Research

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]

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]

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]

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]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

Meta-Analysis of Pulmonary Artery Denervation for Treatment of Pulmonary Hypertension. [2022]

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

Pulmonary artery denervation for pulmonary arterial hypertension. [2021]

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

Long-term mortality after pulmonary artery denervation stratified by baseline functional class in patients with pulmonary arterial hypertension: Long-term mortality after PADN stratified by functional class. [2022]

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

Intravascular Ultrasound Pulmonary Artery Denervation to Treat Pulmonary Arterial Hypertension (TROPHY1): Multicenter, Early Feasibility Study. [2022]

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

Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: Results from PADN-CFDA trial. [2023]

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

Predictors of Serious Adverse Events and High-Level Cardiorespiratory Support in Patients Undergoing Transcatheter Pulmonary Vein Interventions. [2023]

7. United States 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. [2021]

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

Anesthesia in Children With Pulmonary Hypertension: Clinically Significant Serious Adverse Events Associated With Cardiac Catheterization and Noncardiac Procedures. [2022]

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

An Ovine Model for Percutaneous Pulmonary Artery Laser Denervation: Perivascular Innervation and Ablation Lesion Characteristics. [2021]