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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Procedure: PADN
* Procedure: Sham operation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PADN + 5-phosphodiesterase<br>A total of 64 patients are assigned to PADN + 5-phosphodiesterase group after randomization schedule. | Procedure: PADN<br>* 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.<br>* Other names: pulmonary artery denervation;|
| Sham Comparator: Sham operation + 5-phosphodiesterase<br>A total of 64 patients are assigned to sham operation + 5-phosphodiesterase group after randomization schedule. | Procedure: Sham operation<br>* The radiofrequency ablation catheter placed, no ablations for patients in the sham PADN group.<br>|

What is the study measuring?
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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 |