Denervation System for Heart Failure and Pulmonary Hypertension

(PreVail-PH2 Trial)

Recruiting at 7 trial locations

Overseen By Jason McCarthy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Gradient Denervation Technologies

Disqualifiers: Life expectancy < 1 year, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a new procedure might improve life for people with heart failure and Group 2 pulmonary hypertension (PH). The treatment uses a device called the Gradient Denervation System to treat nerves in the pulmonary artery, potentially easing symptoms. Individuals living with heart failure and PH who are on a stable treatment plan may be a good fit for this study. As an unphased trial, participants can contribute to pioneering research that may lead to new treatment options.

Do I need to stop my current medications for the trial?

The trial requires that you have been on stable, guideline-directed medical treatment for at least 3 months before participating, so you should not stop your current medications.

What prior data suggests that the Gradient Denervation System is safe for heart failure and pulmonary hypertension patients?

Research has shown that the Gradient Denervation System for treating the pulmonary artery can be safe for patients. Studies have found that this treatment can significantly improve heart and lung function in patients with heart failure and high blood pressure in the lungs, indicating that the treatment is usually well-tolerated.

Although specific safety data for the Gradient Denervation System is not yet available, similar treatments have shown positive results without major safety issues. The procedure uses sound waves to target nerves in the pulmonary artery, and other studies have achieved this without causing serious side effects.

In summary, while detailed safety data for the Gradient Denervation System itself is lacking, existing evidence from similar treatments suggests it could be a promising and safe option for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Gradient Denervation System is unique because it uses ultrasonic ablation to target and ablate nerves within the pulmonary artery, offering a novel approach for treating heart failure and pulmonary hypertension. Unlike traditional treatments that often focus on managing symptoms with medication or invasive surgery, this system directly addresses nerve activity that contributes to these conditions. Researchers are excited about its potential to provide a less invasive, yet effective, treatment option that could improve outcomes for patients with fewer side effects.

What evidence suggests that the Gradient Denervation System is effective for heart failure and pulmonary hypertension?

Research has shown that pulmonary artery denervation (PADN) can greatly benefit people with heart failure and high blood pressure in the lungs. One study found that PADN improved participants' exercise capacity and heart function. These improvements can ease daily activities and enhance overall quality of life. In this trial, the Gradient Denervation System is being tested as a new device for this treatment. Early results are promising, suggesting it might effectively reduce symptoms and boost heart health in patients. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for heart failure patients with a specific type of high blood pressure in the lungs (Group 2 Pulmonary Hypertension). Participants must have a certain level of heart function, kidney function, and meet other specific health measures. They should be experiencing moderate symptoms but on stable treatment.

Inclusion Criteria

Pulmonary Capillary Wedge Pressure > 15 mmHg (at rest) or > 18 with passive leg raise

Glomerular Filtration Rate (GFR) ≥ 25 ml/min

N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥ 400pg/mL

Exclusion Criteria

Unable to tolerate right heart catheterization

I have severe leakage in my heart valves.

I don't have major issues with my pulmonary artery that would prevent safe treatment.

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 Gradient Denervation System

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Gradient Denervation System

Trial Overview The study is testing the Gradient Denervation System to see if it improves quality of life for these patients. It's an early-stage study focusing on how this procedure affects people with both heart failure and pulmonary hypertension.

How Is the Trial Designed?

Group I: PADN with Gradient Denervation System Experimental Treatment 1 Intervention

Procedure using the Gradient Denervation System to ablate nerves within the pulmonary artery using ultrasonic ablation.

Gradient Denervation System is already approved in United States for the following indications:

Approved in United States as Gradient Denervation System for:

• Investigational use only for Pulmonary Hypertension Group 2 in heart failure patients

Who Is Running the Clinical Trial?

Gradient Denervation Technologies

Lead Sponsor

Trials

3

Recruited

60+

Published Research Related to This Trial

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 patients with advanced heart failure, those with a diastolic pressure gradient (DPG) of ≥7 mmHg showed persistently lower pulmonary capacitance and higher pulmonary vascular resistance after receiving a left ventricular assist device (LVAD), indicating ongoing pulmonary vascular issues.

Despite these residual abnormalities, the increase in peak oxygen uptake (VO2) post-LVAD was similar between patients with DPG ≥7 mmHg and those with DPG <7 mmHg, suggesting that LVADs can improve exercise capacity regardless of initial DPG levels, with improvements linked to reductions in right atrial pressure and increased heart rate during exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of left ventricular assist device therapy in patients with heart failure and mixed pulmonary hypertension. Lim, HS., Howell, N., Ranasinghe, A.[2018]

In a study of 140 patients with mitral valve defects and high pulmonary hypertension, the addition of circular radiofrequency denervation of the pulmonary trunk and pulmonary artery orifices significantly reduced secondary pulmonary hypertension and improved heart chamber remodeling.

This denervation technique also enhanced the outcomes of the Maze IV procedure, leading to better restoration of sinus rhythm in patients, indicating its potential as a safe and effective surgical intervention for those with complicated atrial fibrillation and high pulmonary hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Circular Sympathetic Pulmonary Artery Denervation in Cardiac Surgery Patients With Mitral Valve Defect, Atrial Fibrillation and High Pulmonary Hypertension]. Trofimov, NA., Medvedev, AP., Babokin, VY., et al.[2020]

In a study of patients supported by continuous flow left ventricular assist devices for 30 days to 18 months, higher Doppler blood pressure (DOPBP) levels were linked to a greater risk of adverse events (AEs) such as intracranial hemorrhage and progressive aortic insufficiency.

Patients with high DOPBP (>90 mm Hg) experienced AEs at a rate of 30%, compared to 13% in the intermediate group (80-90 mm Hg) and only 3% in the controlled group (<80 mm Hg), indicating that better blood pressure control may reduce the risk of serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood pressure and adverse events during continuous flow left ventricular assist device support. Saeed, O., Jermyn, R., Kargoli, F., et al.[2015]

In a study of 734 patients implanted with continuous-flow left ventricular assist devices (LVADs), the HeartWare HVAD was associated with a significantly higher risk of stroke compared to the HeartMate II (HR: 1.8), indicating a safety concern for patients using this device.

Overall mortality rates were similar between the two devices (7.3% for HMII and 7.5% for HVAD), but the analysis revealed that while gastrointestinal bleeding and infections were comparable, the HVAD showed a concerning trend of increased stroke risk over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in contemporary continuous-flow left ventricular assist devices: A multi-institutional comparison shows significant differences. Stulak, JM., Davis, ME., Haglund, N., et al.[2015]

In a study of six patients who underwent a device upgrade to the HeartMate 3™ LVAD, the three-year survival rate was 100%, indicating excellent safety and efficacy of the new device.

While the HeartMate 3™ showed superior hemocompatibility and reduced pump thrombosis, there was a high risk of local re-infection in patients who exchanged their devices due to severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year follow-up after less-invasive left ventricular assist device exchange to HeartMate 3™. Hanke, JS., Mariani, S., Merzah, AS., et al.[2022]

In a randomized trial involving 128 patients with WHO group 1 pulmonary arterial hypertension (PAH), pulmonary artery denervation (PADN) significantly improved exercise capacity, as measured by a 33.8 meter increase in 6-minute walk distance compared to a sham procedure over 6 months.

PADN also led to better hemodynamic outcomes, including reduced pulmonary vascular resistance and improved right ventricular function, with fewer clinical worsening events and a higher rate of satisfactory clinical responses compared to the sham group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial. Zhang, H., Wei, Y., Zhang, C., et al.[2023]

In a study of 98 patients with combined precapillary and postcapillary pulmonary hypertension (CpcPH), pulmonary artery denervation (PADN) significantly reduced the rate of clinical worsening compared to the sham + sildenafil group, with only 37.5% of PADN patients experiencing worsening versus 62.0% in the control group over a 3-year follow-up.

PADN also led to notable improvements in exercise capacity, as measured by the 6-minute walk distance, and a reduction in N-terminal pro-B-type natriuretic peptide levels, indicating enhanced cardiac function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3-Year Outcome in Patients With Combined Precapillary and Postcapillary Pulmonary Hypertension: Results From PADN-5 Trial. Zhang, H., Kan, J., Zhang, J., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6614950/

Pulmonary artery denervation improves hemodynamics and ... This study aimed to determine the benefits and correlated mechanisms of pulmonary artery denervation (PADN) for heart failure (HF) pulmonary hypertension (PH).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06052072

NCT06052072 | Pulmonary Artery DenerVation Clinical ... Gradient has developed a novel system for pulmonary artery denervation (PADN) to treat patients with heart failure who also developed pulmonary hypertension (PH) ...

3. jacc.org jacc.org/doi/10.1016/j.jchf.2023.05.016

3-Year Outcome in Patients With Combined Precapillary ... A recent meta-analysis including >1.5 million all-type patients with HF estimated the 1-, 2-, 5-, and 10-year survival rates to be 87%, 73%, 57%, and 35%, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2213177923002524

3-Year Outcome in Patients With Combined Precapillary ... PADN is associated with significant improvements in exercise capacity, cardiac function, and clinical outcomes.

5. tctmd.com tctmd.com/slide/pulmonary-artery-denervation-clinical-study-using-gradient-denervation-system-heart-failure

Pulmonary Artery DenerVation Clinical Study Using the ... Clinical study using the gradient denervation system in heart failure patients with pulmonary hypertension group 2 (PreVail-PH2 Study)

6. facebook.com facebook.com/europeansocietyofcardiology/videos/pulmonary-artery-denervation-clinical-study-using-the-gradient-denervation-syste/3600420910090377/

Pulmonary artery denervation clinical study using the gradient ... Pulmonary artery denervation clinical study using the gradient denervation system in heart failure patients with pulmonary hypertension group 2 ...

7. jacc.org jacc.org/doi/10.1016/j.jcin.2018.09.021

Pulmonary Artery Denervation Significantly Increases 6 ... PADN is associated with significant improvements in hemodynamic and clinical outcomes in patients with CpcPH.