A Trial to Evaluate the Safety and Efficacy of Pulmonary Artery Denervation for the Treatment of Pulmonary Hypertension Associated With Left Heart Failure

Phase 3

Recruiting

• Conditions: Hypertension; Cardiovascular Diseases; Heart Failure With Mid Range Ejection Fraction; Heart Failure With Preserved Ejection Fraction; Pulmonary Hypertension; Heart Failure With Reduced Ejection Fraction; Vascular Diseases; Heart Failure
• Interventions: Procedure: Pulmonary arterial denervation; Drug: Guideline-directed medical therapy (GDMT) for heart failure

• Registration Number: NCT05824923
• Lead Sponsor: Pulnovo Medical (Wuxi) Co., Ltd.

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2023-01-10
• Study First Submitted QC: 2023-04-10
• Study First Posted: 2023-04-24
• Study Start: 2023-08-14
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-20
• Last Update Posted: 2024-03-22
• Primary Completion: 2025-08
• Study Completion: 2027-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 264

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 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pulmonary Artery Denervation (PADN)	Guideline-directed medical therapy (GDMT) for heart failure	Patients in the PADN group will receive pulmonary artery denervation procedure.
Guideline-directed medical therapy (GDMT) for heart failure	Guideline-directed medical therapy (GDMT) for heart failure	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.
Pulmonary Artery Denervation (PADN)	Pulmonary arterial denervation	Patients in the PADN group will receive pulmonary artery denervation procedure.

Primary Outcome Measures

Name	Time	Method
Clinical Worsening, defined as the occurrence of any of the followings:	immediately after the randomization to the last enrolled subject having at least 6 months follow-up	1. Requiring intravenous medication (inotropes, diuretics or vasodilators) due to worsening of heart failure; 2. Rehospitalization due to heart failure; 3. 6MWD decreased by \> 10% or \> 30m compared with baseline; 4. Referral for heart/heart-lung transplantation; 5. All-cause death

Secondary Outcome Measures

Name	Time	Method
Parameters measured by transthoracic echocardiography(TTE)	6 months, 1 year, 3 years	Changes in left ventricular global longitudinal strain (LVGLS) from baseline.
Intravenous medication due to worsening of heart failure	1 month, 6 months, 1 year, 2 years, 3 years	Number of patients requiring intravenous medication (inotropes, diuretics or vasodilators) due to worsening of heart failure
Rehospitalization due to heart failure	1 month, 6 months, 1 year, 2 years, 3 years	Number of patients with rehospitalization due to heart failure
N-terminal pro-B-type natriuretic peptide (NT-proBNP)	6 months	Changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline
Changes in the Kansas City Cardiomyopathy Questionnaire(KCCQ) overall summary score from baseline	1 month, 6 months, 1 year, 2 years, 3 years	The KCCQ is a self-administered, 23-item questionnaire to provide a better description of quality of life in patients with heart failure. The overall summary score range from 0 to 100, higher score means higher quality of life.
6 minute walk distance(6MWD) difference from baseline	6 months, 1 year, 3 years	The 6MWD test was conducted according to the American Thoracic Society guidelines.
All-cause death	1 month, 6 months, 1 year, 2 years, 3 years	Number of death due to any cause
Heart/heart-lung transplantation	1 month, 6 months, 1 year, 2 years, 3 years	Number of patients referred for heart/heart-lung transplantation

Trial Locations

Locations (1)

General Hospital of Northern Theater Command; 🇨🇳 Shenyang, Liaoning, China