Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— PADN-CFDA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03282266
• Other study ID #: NFH20170501
• Status: Completed
• Phase: N/A
• Start date: January 18, 2018
• Est. completion date: December 22, 2021

Study information

• Verified date: March 2022
• Source: Nanjing First Hospital, Nanjing Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: December 22, 2021
• Est. primary completion date: June 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

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.
• Sham operation
The radiofrequency ablation catheter placed, no ablations for patients in the sham PADN group.

Locations

Country	Name	City	State
China	Nanjing First Hospital	Nanjing	Jiangsu

Sponsors (10)

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

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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