Clinical trial NCT03282266: Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension
Official title: A Randomised, Single-blind, Sham Operation-controlled Study to Evaluate the Safety and Efficacy of the Pulmonary Artery Denervation for the Treatment of Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Nanjing First Hospital, Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Pulnovo Medical (Wuxi) Co., Ltd.
name: Guangdong Provincial People's Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Tianjin Medical University General Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: Beijing Anzhen Hospital
name: Shenyang Northern Hospital
name: The Second Affiliated Hospital of Chongqing Medical University
name: Tongji Hospital
First posted: 2017-09-13
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this randomized control trial is to gain clinical insight on the use of pulmonary artery denervation (PADN) for the treatment of pulmonary arterial hypertension (PAH). The primary objective is to assess effectiveness and safety of PADN for the treatment of PAH.

Detailed description: The current study is designed as a multicenter, randomized and prospective study aiming to compare the change in 6-minute walk distance (6MWD) of PADN on PAH patients. Based on the previous studies, the 6MWD was 13±24 m after 6-month treatment using target drugs. And our previous data showed that 6MWD at 6-month after PADN procedure was 65±85 m. As a result, a total of 128 patients with Group I PAH are randomized at a ratio of 1:1 to either PADN procedure plus phosphodiesterase-5 inhibitors (PDE5i) group (PADN group) or sham-PADN procedure plus PDE5i group (Sham group) using a randomization schedule blocked by site. The combination therapy of PDE5i with additional other PAH-specific target drugs is not recommended for all patients and is left at physician's discretion in both groups.

Eligibility criteria: Inclusion Criteria:

Provision of informed consent prior to any study specific procedures; Men and women 18 years and older; Group I PAH, defined as a mPAP≥25mmHg, PCWP\<15mmHg and PVR\[The PVR =(mPAP-PCWP)/CO\]\>3.0 Woods unit.

Exclusion Criteria:

General exclusion criteria:

Pregnancy and breast feeding mother; Estimated life expectancy \< 12 months; Scheduled major surgery in the next 6 months; Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk; Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 30 days.

Procedural exclusion criteria:

WHO group II, III, IV, V PH Severe Renal dysfunction (Ccr\<30 ml/min) Blood platelet count\<100,000/L Expected life span\<6-month Systematical inflammation Malignant cancer(s) Tricuspid valve stenosis, Supra-pulmonary valve stenosis Allergic to studied drugs or metal materials.

Primary outcomes:
measure: Change From Baseline in 6-Minute Walk Distance (6MWD) at 6 Month
timeFrame: Baseline, 6 Month
Secondary outcomes:
measure: Change From Baseline in Systolic Pulmonary Arterial Pressure (sPAP) at 6 Month
timeFrame: Baseline, 6 Month
measure: Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at 6 Month
timeFrame: Baseline, 6 Month
measure: Change From Baseline in Cardiac Output (CO) at 6 Month
timeFrame: Baseline, 6 Month
measure: Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 6 Month
timeFrame: Baseline, 6 Month
measure: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 6 Month
timeFrame: Baseline, 6 Month
measure: Change From Baseline in Right Ventricle Functional at 6 Month
timeFrame: Baseline, 6 Month
measure: PAH-related events
timeFrame: 6 Month
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
Study officials:
affiliation: Nanjing First Hospital, Nanjing Medical University
name: Shao-Liang Chen, MD, PhD
role: STUDY_CHAIR
References:
citation: Chen SL, Zhang FF, Xu J, Xie DJ, Zhou L, Nguyen T, Stone GW. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J Am Coll Cardiol. 2013 Sep 17;62(12):1092-1100. doi: 10.1016/j.jacc.2013.05.075. Epub 2013 Jul 10.
citation: Chen SL, Zhang H, Xie DJ, Zhang J, Zhou L, Rothman AM, Stone GW. Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study. Circ Cardiovasc Interv. 2015 Nov;8(11):e002837. doi: 10.1161/CIRCINTERVENTIONS.115.002837.
citation: Zhang H, Wei Y, Zhang C, Yang Z, Kan J, Gu H, Fan F, Gu H, Wang Q, Xie D, Zhang G, Guo X, Yin Y, Jin B, Zhou H, Yang Z, Wang Z, Xin Y, Zhang C, Meng L, Wang X, Sun J, Zhao C, Zhang J, Yan X, Chen F, Yao C, Stone GW, Chen SL. Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial. JACC Cardiovasc Interv. 2022 Dec 12;15(23):2412-2423. doi: 10.1016/j.jcin.2022.09.013. Epub 2022 Sep 18.