Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension (PADN-CFDA)

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Procedure: PADN; Procedure: Sham operation

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.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PADN + 5-phosphodiesterase; A total of 64 patients are assigned to PADN + 5-phosphodiesterase group after randomization schedule.	Procedure: PADN; PADN was performed at three sites at the conjunctional area between the distal main trunk and the ostial left branch. The following ablation parameters were programmed at each point: a temperature of 45 ℃-50 ℃, energy ≤15 W, and a time of 120 seconds. The procedure would cease for 10 seconds if the patient felt intolerable chest pain during the procedure. The EKG and pressure lines (including cardiac output) were monitored and continuously recorded throughout the procedure.; Other Names: pulmonary artery denervation
Sham Comparator: Sham operation + 5-phosphodiesterase; A total of 64 patients are assigned to sham operation + 5-phosphodiesterase group after randomization schedule.	Procedure: Sham operation; The radiofrequency ablation catheter placed, no ablations for patients in the sham PADN group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 6-Minute Walk Distance (6MWD) at 6 Month	6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.	Baseline, 6 Month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Systolic Pulmonary Arterial Pressure (sPAP) at 6 Month	sPAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.	Baseline, 6 Month
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at 6 Month	mPAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.	Baseline, 6 Month
Change From Baseline in Cardiac Output (CO) at 6 Month	CO is the volume of blood being pumped by the heart ventricle in the time interval of one minute.	Baseline, 6 Month
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 6 Month	PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.	Baseline, 6 Month
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 6 Month	PVR: calculated by subtracting PCWP from mPAP and dividing by cardiac output in pulmonary circulation (COpulm).	Baseline, 6 Month
Change From Baseline in Right Ventricle Functional at 6 Month	Right ventricle functional measures by echocardiography include right ventricle systolic and diastolic functional variables.	Baseline, 6 Month
PAH-related events	PAH-related events were defined as those caused by worsening of PAH, initiation of treatment with intravenous or subcutaneous prostanoids, lung transplantation, atrial septostomy, or all-cause mortality.	6 Month

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University
• Collaborators: Tongji Hospital; First Affiliated Hospital Xi'an Jiaotong University; The First Affiliated Hospital of Zhengzhou University; Guangdong Provincial People's Hospital; Beijing Anzhen Hospital; Tianjin Medical University General Hospital; The Second Affiliated Hospital of Chongqing Medical University; Shenyang Northern Hospital; Pulnovo Medical (Wuxi) Co., Ltd.

Publications and helpful links

General Publications

• 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.
• 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.
• 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 Trial. JACC Cardiovasc Interv. 2022 Sep 9:S1936-8798(22)01754-X. doi: 10.1016/j.jcin.2022.09.013. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2018
• Primary Completion (Actual): June 22, 2021
• Study Completion (Actual): December 22, 2021

Study Registration Dates

• First Submitted: September 12, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 26, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: NFH20170501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No