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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 75 Years
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05824923
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Pulnovo Medical (Wuxi) Co., Ltd.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Yaling Han
Principal Investigator Affiliation	The General Hospital of Northern Theater Command
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry, Other
Overall Status	Recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Pulmonary Hypertension, Heart Failure With Reduced Ejection Fraction, Hypertension, Vascular Diseases, Cardiovascular Diseases, Heart Failure, Heart Failure With Preserved Ejection Fraction, Heart Failure With Mid Range Ejection Fraction

Additional Details

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.

Arms & Interventions

Arms

Experimental: Pulmonary Artery Denervation (PADN)

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

Active Comparator: 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.

Interventions

Procedure: - Pulmonary arterial denervation

Contrast pulmonary artery (PA) angiography will be performed to localize the pulmonary artery bifurcation level and calculate the PA diameter. Once the anatomy deemed acceptable, the radiofrequency ablation catheter will be introduced into ostium of the left PA and the distal bifurcation area of the main PA. The catheter will be manoeuvred within the PA to allow energy delivery in a circumferential manner to ensure that the electrodes are tightly in contact with the endovascular surface. About three ablations at 45-55 ℃ for 120 seconds each will be performed in ostium of the left PA and the distal bifurcation area of the main PA. For non-atrial fibrillation patients, dual antiplatelet therapy for 1 month after PADN is recommended. Patients with atrial fibrillation should continue new oral anticoagulants and patients who underwent metal valve replacement should continued oral warfarin anticoagulation according to guidelines, which could determined by the physician.

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

GDMT medication recommendation including: Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI) Beta-receptor blocker (BB) Mineralocorticoid receptor antagonist (MRA) Sodium-glucose co-transporter 2 (SGLT2) inhibitor Diuretics The medication regimen (type and dosage) will be the investigator's discretion in accordance with the 2023 ESC Guidelines for Heart Failure. The type and dosage of all GDMT medications (except for diuretics) should remain unchanged through follow-up duration (at 12-month visit), unless the participant's conditions need adjust of GDMT regimens. Dosage and single or combination of diuretics are all left at physician's discretion.

Contact a Trial Team

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