Clinical trial NCT05824923: A Trial to Evaluate the Safety and Efficacy of Pulmonary Artery Denervation for the Treatment of Pulmonary Hypertension Associated With Left Heart Failure
Official title: A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of Single-use Ring-shaped Pulmonary Artery Radiofrequency (RF) Ablation Catheter and Pulmonary Artery RF Ablation Generator for the Treatment of Pulmonary Hypertension Associated With Left Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: 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
Keywords: Pulmonary Artery Denervation
Pulmonary Hypertension Due to Left Heart Disease
Heart Failure
pulmonary hypertension
left heart failure
Lead sponsor: Pulnovo Medical (Wuxi) Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The General Hospital of Northern Theater Command
name: The First Affiliated Hospital with Nanjing Medical University
name: First Hospital of Tsinghua University
name: Cangzhou Central Hospital
name: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Guangdong Provincial People's Hospital
name: The First Affiliated Hospital of Guangzhou Medical University
name: First Affiliated Hospital of Harbin Medical University
name: Tongji Hospital
name: Second Hospital of Jilin University
name: China-Japan Union Hospital, Jilin University
name: Shanxi Cardiovascular Hospital
name: RenJi Hospital
name: Shanghai 10th People's Hospital
name: Beijing Anzhen Hospital
name: West China Hospital
name: Sichuan Academy of Medical Sciences
name: The First Affiliated Hospital of Soochow University
name: TEDA International Cardiovascular Hospital
name: Tianjin Medical University General Hospital
name: Renmin Hospital of Wuhan University
name: Zhongnan Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: Xiamen Cardiovascular Hospital, Xiamen University
name: Zhejiang University
name: Shengjing Hospital
name: First Affiliated Hospital of Fujian Medical University
name: First Affiliated Hospital of Wenzhou Medical University
name: Gansu Provincial Hospital
name: Yanan Hospital of Kunming City
name: First Affiliated Hospital of Chongqing Medical University
name: Huaihe Hospital of Henan University
name: Wuhan Union Hospital, China
name: The First Affiliated Hospital of Nanchang University
name: Hunan Provincial People's Hospital
name: Tianjin Medical University Second Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: The First Hospital of Jilin University
First posted: 2023-04-24
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: At the 12-months visit, participants in the control group who still meet the inclusion and exclusion criteria can choose to receive PADN procedure.
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: Clinical Worsening, defined as the occurrence of any of the followings:
timeFrame: immediately after the randomization to the last enrolled subject having at least 6 months follow-up
Secondary outcomes:
measure: Parameters measured by transthoracic echocardiography(TTE)
timeFrame: 6 months, 1 year, 3 years
measure: Parameters measured by transthoracic echocardiography(TTE)
timeFrame: 6 months, 1 year, 3 years
measure: Parameters measured by transthoracic echocardiography(TTE)
timeFrame: 6 months, 1 year, 3 years
measure: Parameters measured by transthoracic echocardiography(TTE)
timeFrame: 6 months, 1 year, 3 years
measure: Parameters measured by transthoracic echocardiography(TTE)
timeFrame: 6 months, 1 year, 3 years
measure: Parameters measured by transthoracic echocardiography(TTE)
timeFrame: 6 months, 1 year, 3 years
measure: Parameters measured by transthoracic echocardiography(TTE)
timeFrame: 6 months, 1 year, 3 years
measure: Parameters measured by transthoracic echocardiography(TTE)
timeFrame: 6 months, 1 year, 3 years
measure: N-terminal pro-B-type natriuretic peptide (NT-proBNP)
timeFrame: 6 months
measure: 6 minute walk distance(6MWD) difference from baseline
timeFrame: 6 months, 1 year, 3 years
measure: Changes in the Kansas City Cardiomyopathy Questionnaire(KCCQ) overall summary score from baseline
timeFrame: 1 month, 6 months, 1 year, 2 years, 3 years
measure: Intravenous medication due to worsening of heart failure
timeFrame: 1 month, 6 months, 1 year, 2 years, 3 years
measure: Rehospitalization due to heart failure
timeFrame: 1 month, 6 months, 1 year, 2 years, 3 years
measure: Heart/heart-lung transplantation
timeFrame: 1 month, 6 months, 1 year, 2 years, 3 years
measure: All-cause death
timeFrame: 1 month, 6 months, 1 year, 2 years, 3 years
Other outcomes:
measure: Safety Outcome: AESI
timeFrame: within 30 days after the procedure
measure: Safety Outcome: AE and SAE
timeFrame: throughout the clincialtrial
Locations:
city: Shenyang
country: China
facility: General Hospital of Northern Theater Command
state: Liaoning
Study officials:
affiliation: The General Hospital of Northern Theater Command
name: Yaling Han
role: PRINCIPAL_INVESTIGATOR
References: