A Trial to Evaluate the Safety and Efficacy of Pulmonary Artery Denervation for the Treatment of Pulmonary Hypertension Associated With Left Heart Failure (PADN-HF-PH)

Pulnovo Medical

Status and phase: Enrolling; Phase 3

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

Treatments: Procedure: Pulmonary arterial denervation; Drug: Guideline-directed medical therapy (GDMT) for heart failure

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05824923

Pulnovo-CO-2022-01

Details and patient eligibility

About

It's a phase III, prospective, multicenter, randomized controlled trial to evaluate the safety and efficacy of the pulmonary artery denervation (PADN) for heart failure (HF) patients diagnosed with pulmonary hypertension associate with left heart disease (PH-LHD) by right heart catheterization.

Full description

Chronic heart failure (CHF) patients who have received guideline-directed medical therapy (GDMT) based on the 2023 ESC Guidelines for HF and have reached clinical stable, and diagnosed with PH-LHD by right heart catheterization, will be randomized to the PADN group or control group in a 1:1 ratio to receive PADN combined with HF GDMT or HF GDMT, respectively. After the 12-month follow-up visit is completed, participants in the control group who still meet the inclusion and exclusion criteria can also choose to receive PADN.

Approximately 264 participants will be enrolled at up to 39 centers in China and followed for 3 years. The safety and efficacy of the PADN system, including RF ablation catheter and generator will be evaluated by comparing the therapeutic effect of the PADN group and the control group.

Enrollment: 264 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥18, ≤75 years old;

2. Diagnosed with chronic heart failure for at least 3 months, and have received the GDMT pharmacological treatment based on the 2023 ESC Guidelines for Heart Failure for at least 1 month;

3. Clinically stable defined by

   1. No intravenous diuretics, inotropes or vasodilators for at least 1 month, and
   2. Systolic blood pressure (SBP) ≥ 100 and < 160 mmHg and resting heart rate (HR) ≥50 and <100 bpm (<110 bpm for atrial fibrillation) on the day of the procedure

4. New York Heart Association (NYHA) class II-IVa;

5. 6MWD ≥ 100 m and < 450 m;

6. NT-proBNP > 125 pg/mL (BNP > 35 pg/mL);

7. Hemodynamic indicators (RHC) :

   1. Mean pulmonary arterial pressure (mPAP) > 20 mmHg
   2. Pulmonary capillary wedge pressure (PCWP) >15 mmHg

8. Understand and be willing to sign informed consent, and be willing to follow the follow-up plan required by the protocol.

Exclusion criteria

1. Any of the following:

   1. Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction or systolic anterior motion; pericardial disease; infiltrative or inflammatory myocardial disease; valvular stenosis of any of the 4 valves, or severe regurgitation of aortic and pulmonary valves, or active endocarditis; or
   2. Symptomatic carotid stenosis, or transient ischemic attack (TIA) or stroke within 30 days prior to randomization; or
   3. Untreated congenital heart disease; or
   4. Have received any revascularization, including coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within 6 months prior to randomization; or anticipated to undergo coronary revascularization (CABG or PCI) within 6 months; or
   5. Artificial pacemakers, including single-chamber, dual-chamber and three-chamber pacemakers, have been implanted or are anticipated to be implanted within 6 months; or
   6. Anticipated to undergo ablation of atrial fibrillation within 6 months; or
   7. Anticipated to undergo heart valve surgery (valve replacement, valvuloplasty) within 6 months; or
   8. Listing for heart/heart-lung transplantation or anticipated to implant a ventricular assist device (VAD)

2. Other types of pulmonary hypertension, including WHO Group1, Group3, Group4, Group5;

3. Received pulmonary arterial hypertension (PAH) targeted drugs within 1 month prior to randomization;

4. Anticipated to undergo any surgery within 6 months;

5. The cardiac index (CI) of RHC < 1.5L/min/m²;

6. Severe renal insufficiency (eGFR <30mL/min/1.73m² by MDRD formula);

7. Severe liver insufficiency (Child-Pugh classification C);

8. Platelet count < 50 × 10^9/L;

9. Life expectancy <1 year;

10. Systemic inflammation or other disease requiring long-term use of glucocorticoids or immunosuppressants;

11. Active infection requiring oral or intravenous antibiotics;

12. Body mass index (BMI) >40 kg/m²;

13. Pregnant or lactating women, or plan to pregnant in one year;

14. Participated in other clinical trials within 3 months prior to signing the informed consent;

15. Any other circumstances that investigators deem inappropriate to participate in this trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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264 participants in 2 patient groups

Pulmonary Artery Denervation (PADN)

Experimental group

Description:

Patients in the PADN group will receive pulmonary artery denervation procedure.

Treatment:

Drug: Guideline-directed medical therapy (GDMT) for heart failure

Procedure: Pulmonary arterial denervation

Guideline-directed medical therapy (GDMT) for heart failure

Active Comparator group

Description:

Patients in the control group will take their baseline anti-heart failure medications at the original doses according to 2023 ESC Guidelines for heart failure, without any changes except when medically required. The anti-heart failure drugs treatment is consistent in both arms.

Treatment:

Drug: Guideline-directed medical therapy (GDMT) for heart failure