A Randomized Placebo-procedure Controlled Trial of the Enhancor System (PULmonary Artery Denervation) to Evaluate Safety and Efficacy in Patients With Combined Pre- and Post-capillary Pulmonary Hypertension Associated With Left Heart Disease

NCT07214376 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: Pulnovo-CO-2025-01
• Study Type: interventional
• Target: 750
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical study is to evaluate the safety and efficacy of percutaneous pulmonary artery denervation with the Multi-Pole Pulmonary Artery Radiofrequency Ablation Enhancor System in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) associated with left heart disease (LHD). This randomized control trial will compare the investigational device (The Enhancor System) to control (medical therapy.) Participants who will consist of patients with chronic heart failure (HF) who are receiving maximally tolerated guideline-directed medical therapy (GDMT) for left heart failure, are clinically stable, and who have been diagnosed with CpcPH by right heart catheterization (RHC), will be treated with PADN and followed for 3 years.

Conditions

Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure With Preserved Ejection Fraction; Heart Failure With Mid Range Ejection Fraction; Pulmonary Hypertension; Heart Failure With Reduced Ejection Fraction

Keywords

Pulmonary Artery Denervation; Pulmonary Hypertension Due to Left Heart Disease; Heart Failure; pulmonary hypertension; left heart failure

Outcome Measures

Primary Outcomes (2)

• Primary Efficacy Endpoint

  Composite of Major Heart Failure Events (MHFE). Based on a time-to-first event analysis at 24-month follow-up evaluated when the last enrolled patient reaches 12-month follow-up: 1. Cardiovascular death; 2. Heart transplantation or durable left ventricular assist device (LVAD) implantation; 3.HF hospitalizations; 4. Outpatient worsening HF events

  Immediately after the randomization to last enrolled patient reaches 12-month follow-up

• Primary Safety Endpoint

  Composite of Device-related or Procedre-related Major Adverse Events (MAEs) in the treatment group compared with a performance goal

  30-days

Secondary Outcomes (13)

• Cumulative incidence of Major Heart Failure Events

  30days, 6 months, 12 months, 24 months, and 36 months

• Outpatient worsening HF events

  30days, 6 months, 12 months, 24 months, and 36 months

• All cardiovascular hospitalizations

  30days, 6 months, 12 months, 24 months, and 36 months

• N-terminal pro-B-type natriuretic peptide (NT-proBNP)

  6 months, 12 months, 24 months, and 36 months

• 6 minute walk distance(6MWD)

  6 months, 12 months, 24 months, and 36 months

Other Outcomes (1)

• Device-related or Procedure-related Major Adverse Events

  30 days, 6 months, 12 months, 24 months, and 36 months

Study Arms (2)

Pulmonary Artery Denervation (PADN)

EXPERIMENTAL

PADN plus GDMT

Device: Pulmonary Artery Denervation (PADN)

Control

ACTIVE COMPARATOR

Placebo-procedure plus GDMT

Device: Sham procedure control

Interventions

Pulmonary Artery Denervation (PADN) DEVICE

In patients randomized to Intervention, a Contrast pulmonary artery (PA) angiography will be performed to identify the pulmonary artery bifurcation and measure the PA diameter. Once the anatomy is deemed suitable, a radiofrequency ablation catheter will be introduced into the ostium of the left PA and the distal bifurcation of the main PA. The catheter will be maneuvered within the PA to deliver energy circumferentially, ensuring tight electrode contact with the endovascular surface. Approximately three ablations will be performed at a target temperature of 50 °C (range 45-55 °C) for 120 seconds each at both the left PA ostium and the distal main PA bifurcation. All patients enrolled in this clinical study will following the Guideline-Directed Medical Therapy (GDMT)

Pulmonary Artery Denervation (PADN)

Sham procedure control DEVICE

In patients randomized to a placebo-procedure, a script will be followed for approximately 20 minutes to simulate the PADN procedure. All patients enrolled in this clinical study will following the Guideline-Directed Medical Therapy (GDMT)

Control

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥18 and ≤85 years of age
• Subject is diagnosed with chronic HF due to left-sided heart disease for at least 6 months prior to screening (regardless of LVEF), and remains symptomatic despite maximally tolerated class I GDMT for left heart failure and CRT as appropriate per US or EU guidelines according to region of enrollment
• Subject is clinically stable, defined as:
• No hospitalizations for heart failure for at least 1 month; no major changes in societal guideline-recommended class I oral GDMT for left heart failure for at least 1 month; no CRT or ICD implant in the prior 3 months; and no anticipated major changes in any HF-GDMT (other than possibly diuretic dose) or planned cardiac rhythm management device implantation after the procedure
• SBP is ≥90 and ≤160 mmHg and resting HR is ≥50 and ≤100 bpm (≤110 bpm for atrial fibrillation)
• PASP (RVSP) is ≥30 mmHg on the baseline TTE.
• Subject has New York Heart Association (NYHA) class II, III or IVa symptoms (IVa is defined as symptoms with minimal exertion or at rest, but the patient is able to ambulate and does not require continuous intravenous medications).
• Subject has 6MWD at baseline ranging from 100 to 450 m limited by dyspnea or fatigue and not orthopedic or other non-HF-related issues
• Subject has NT-proBNP ≥600 pg/mL for patients with LVEF ≤40% or ≥200 pg/mL for patients with LVEF \>40% at the time of screening (a central lab will be made available for sites that cannot measure NT-proBNP)
• Subject is able and willing to follow all aspects of the research protocol including medication compliance and follow-up visits and testing.
• Subject or the subject's legally designated representative signs an IRB/EC approved informed consent form prior to study participation.

You may not qualify if:

• Subject has a life expectancy of less than 1 year due to non-cardiovascular causes.
• Subject has known hypertrophic cardiomyopathy with either left ventricular (LV) outflow tract obstruction or systolic anterior motion (SAM) of the anterior leaflet of the mitral valve; pericardial disease; or infiltrative or active inflammatory myocardial disease, including known amyloidosis
• Subject has severe stenosis or regurgitation of any heart valve, moderate or severe stenosis of the aortic valve, or any degree of stenosis of the pulmonic valve
• Subject has symptomatic carotid stenosis, or transient ischemic attack (TIA) or stroke in the prior 30 days or any prior stroke with a permanent residual deficit with modified Rankin Scale (mRS) score ≥4
• Subject has any prior intracranial hemorrhage with or without a residual deficit, or any known intracranial pathology pre-disposing to bleeding (e.g. mass, AV fistula, aneurysm, etc.)
• Subjects with a known bleeding diathesis or who will refuse blood transfusions
• Subjects allergic to heparin (including heparin induced thrombocytopenia), unless bivalirudin or argatroban can be used for procedural anticoagulation
• Subjects with life threatening allergy to contrast dye that cannot be adequately pre-medicated, or any prior contrast-related anaphylaxis
• Subject has congenital heart disease other than mitral valve prolapse or a PFO
• Subject had coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in the prior 6 months or is anticipated to undergo CABG or PCI within 12 months after randomization.
• Subject has any pacemaker with an intracardiac sensing or pacing lead or wire implanted in the prior 3 months, or CardioMEMS HF System or other intracardiac pressure monitoring system, or cardiac contractility modulation system or baroreceptor activation therapy implanted within the prior 3 months, or any plans to implant any of these devices within 12 months after the procedure.
• Subject has undergone atrial fibrillation ablation within the prior 6 months or is anticipated to undergo atrial fibrillation ablation within 12 months after randomization.
• Subject has undergone heart valve surgery or transcatheter valve intervention within the prior 6 months or is anticipated to undergo heart valve surgery or transcatheter valve intervention (e.g., valve repair or replacement, valvuloplasty) within 12 months after randomization.
• Subject has any tricuspid or pulmonic valve implants (implanted annuloplasty rings are allowed).
• Subject has an inferior vena cava (IVC) filter implant.

Sponsors & Collaborators

• Pulnovo Medical, Inc.: lead

MeSH Terms

Conditions

Hypertension, Pulmonary; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Failure

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Heart Diseases

Study Officials

• Gregg W. Stone

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MOFFETT LAURA MARY GINTANT

CONTACT

+1 952 303 2821; laura.moffett@pulnovomed.com

Mark Gu

CONTACT

+08 13774217349; mark.g@pulnovomed.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: CEC members
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: At 24 months, control subjects who have experienced a primary efficacy endpoint event and who still meet all eligibility criteria will be offered the opportunity to cross over to the PADN plus GDMT group

Study Record Dates

• First Submitted: October 7, 2025
• First Posted: October 9, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: March 12, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share