Pulmonary Artery Denervation for Heart Failure With Preserved Left Ventricular Ejection Fraction

NCT07331220 | Not Yet Recruiting DMC

• 1 other identifier: KY20250425-06
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the impact of PADN combined with guideline-directed medical therapy (GDMT) versus a sham procedure with GDMT on clinical outcomes in heart failure (HF) patients with preserved left ventricular ejection fraction (LVEF\>40%). Outcomes include cardiovascular death, HF-related rehospitalization, requirement for heart transplantation or need of valvular treatment or LVAD or pacemaker implantation, and worsening in outpatients (defined as requirement for intravenous therapy or diuretic intensification, including increasing the types or dose of diuretics).

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

Pulmonary artery denervation; Heart failure with preserved ejection fraction; Guideline-directed medical therapy; Clinical worsening

Outcome Measures

Primary Outcomes (1)

• Clinical worsening

  A composite of clinical worsening at 12 months, including cardiovascular death, HF-related rehospitalization, requirement for heart transplantation, need of valvular treatment or LVAD or pacemaker implantation, and worsening in outpatients (defined as requirement for intravenous therapy or diuretic intensification, including increasing the types or dose of diuretics).

  From randomization to 12 months

Secondary Outcomes (13)

• Clinical worsening

  From baseline to 24 months

• Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS)

  From baseline to 12 months

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

  From baseline to 1 month, 6 months, and 12 months

• 6-minute walk distance (6MWD)

  From baseline to 1 month, 6 months, and 12 months

• KCCQ-CSS increase ≥6 points

  From baseline to 12 months

Other Outcomes (9)

• Loop diuretic dose

  From baseline to 12 months

• SGLT2i dose

  From baseline to 12 months

• NYHA functional class

  From baseline to 12 months

Study Arms (2)

PADN plus GDMT

EXPERIMENTAL

Pulmonary artery denervation combined with guideline-directed medical therapy.

Procedure: PADN; Drug: GDMT

Sham procedure plus GDMT

PLACEBO COMPARATOR

Sham procedure combined with guideline-directed medical therapy

Procedure: Sham procedure; Drug: GDMT

Interventions

PADN PROCEDURE

Advancing the pulmonary artery denervation catheter with a diameter to vessel of 1.1\~1.2:1 through the long sheath to the left pulmonary artery ostium. Connecting the catheter to the RF generator. Rotate the catheter under imaging so the premounted electrodes tightly contact the target ablation positions. Recommended temperature-controlled mode, set temperature to 50°C, ablation time to 150 seconds (with effective ablation time of 120 seconds, defined as the tissue temperature reaches 45°C-55°C. Ablation is performed at a total of 3 sites with 120 seconds for each.

Also known as: Pulmonary artery denervation, Right heart catheterization

PADN plus GDMT

Sham procedure PROCEDURE

The ablation catheter under imaging guidance will be advanced to the target ablation points, but DO NOT connect the ablation catheter to the RF generator; DO NOT deliver RF energy. The operator issues commands to "start" and "stop" RF ablation, simulating the sound of the PADN RF generator for at least 2 minutes (using a pre-recorded MP4).

Sham procedure plus GDMT

GDMT DRUG

GDMT regimen including sodium-glucose co-transporter 2 inhibitor (SGLT2i) + spironolactone. SGLT2i can be dapagliflozin or empagliflozin. * Dapagliflozin: Target maintenance dose 10 mg/day. Contraindicated if eGFR persistently \<25 mL/min/1.73 m². * Empagliflozin: Target maintenance dose 10 mg/day. Contraindicated if eGFR persistently \<20 mL/min/1.73 m². * Spironolactone: Starting dose 10-20 mg/day, maximum dose 40 mg/day. Suspend if serum potassium is \>5.5 mmol/L; restart at half dose after correction. Permanently discontinue if serum potassium is \>6.0 mmol/L. Suspend and evaluate if eGFR persistently declines \>30% or \<30 mL/min/1.73 m². Other medications are left at the physician's discretion.

Also known as: Guideline-directed medical therapy

PADN plus GDMT; Sham procedure plus GDMT

Eligibility Criteria

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

You may qualify if:

• \. The subject, or their legal guardian, must have a clear understanding of the trial's design and treatment procedures. They must provide written informed consent before any trial-specific tests or procedures are conducted.
• \. Both male and female subjects age between 18 \~ 85 years old. 3. Dyspnea on exertion (NYHA functional class II-IV) not explained by non-cardiac or ischemic etiology.
• \. LVEF \>40% on imaging within 24 months prior to enrollment, with no clinical changes suggesting worsening systolic function.
• \. Elevated NT-proBNP or BNP levels meeting the following thresholds stratified by age and atrial fibrillation (AF) status:
• Patients WITHOUT atrial fibrillation:
• Age \<50 years: BNP \>100 pg/mL or NT-proBNP \>450 pg/mL
• Age 50-75 years: BNP \>150 pg/mL or NT-proBNP \>900 pg/mL
• Age \>75 years: BNP \>200 pg/mL or NT-proBNP \>1800 pg/mL
• Patients WITH atrial fibrillation:
• BNP \>150 pg/mL or NT-proBNP \>300 pg/mL
• \. Stable HF GDMT (no change in either types or dose) for ≥14 days prior to enrollment, including SGLT2i and spironolactone. Other medication, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI, sacubitril/valsartan), beta-blockers, or calcium channel blockers (CCBs), were left at physician's discretion.
• \. Dose changes of ACEIs, ARBs, sacubitril/valsartan, beta-blockers, or CCBs did not exceed 100% of baseline dose (i.e., no doubling or halving).
• \. Continuous diuretic use for ≥14 days prior to screening, with stable dose in the last 7 days.
• \. Meet at least one of the following:
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You may not qualify if:

• Hospitalization for HF within 7 days prior to screening.
• Participation in an interventional trial (using investigational drug or device) of a non-observational registry study within 14 days prior to screening.
• History of blood or bone marrow donation within 4 weeks prior to screening, or planned donation during the study.
• Implantation of pulmonary artery pressure monitor or pacemaker within 4 weeks prior to screening, or planned implantation during the study.
• Hospitalization within 30 days prior to screening for: acute ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), unstable angina, percutaneous coronary intervention (PCI), or cardiac surgery.
• Cardiac resynchronization therapy (CRT) within 90 days prior to screening.
• Planned revascularization (PCI or CABG), major cardiac surgery (including coronary artery bypass grafting, valve replacement, ventricular assist device implantation, heart transplantation, other surgery requiring thoracotomy), transcatheter aortic valve replacement (TAVR), or CRT implantation within 90 days after screening.
• History of femoral or jugular vein surgery.
• Life expectancy \<1 year at screening.
• Estimated glomerular filtration rate (eGFR) \<20 ml/min/1.73 m² at screening (calculated using the modified MDRD formula).
• BNP \<150 pg/ml and NT-proBNP \<300 pg/ml at screening.
• Serum potassium \>5.5 mmol/L at screening.
• Physical examination showing volume depletion at screening or randomization.
• Mean supine systolic blood pressure \<100 mmHg at screening or randomization.
• Uncontrolled hypertension, defined as mean supine systolic blood pressure ≥160 mmHg (average of three measurements) at screening.

Sponsors & Collaborators

• Nanjing First Hospital, Nanjing Medical University: lead
• Nanjing Medical University: collaborator

Study Sites (1)

Nanjing First Hospital, Nanjing Medical University

Nanjing, Jiangsu, 210006, China

Location

Study Officials

• Shao-Liang Chen, MD

  Nanjing First Hospital, Nanjing Medical University

  STUDY CHAIR

Central Study Contacts

Shao-Liang Chen, MD

CONTACT

+86-25-52271351; chmengx@126.com

Jing Kan, PhD

CONTACT

+86-25-52279862; kanjingok@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Staff from the core laboratories
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients will be assigned to undergo either PADN plus GDMT or sham procedure plus GDMT

Study Record Dates

• First Submitted: December 8, 2025
• First Posted: January 9, 2026
• Study Start: December 30, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: January 9, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: It will be available after 6 months since publication of this trial, unless PI agreed earlier.
• Access Criteria: upon approval by PI of this trial

Locations

CN (1)