The goal of this clinical study is to evaluate the safety and efficacy of percutaneous pulmonary artery denervation with the Multi-Pole Pulmonary Artery Radiofrequency Ablation Enhancor System in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) associated with left heart disease (LHD). This randomized control trial will compare the investigational device (The Enhancor System) to control (medical therapy.) Participants who will consist of patients with chronic heart failure (HF) who are receiving maximally tolerated guideline-directed medical therapy (GDMT) for left heart failure, are clinically stable, and who have been diagnosed with CpcPH by right heart catheterization (RHC), will be treated with PADN and followed for 3 years.
Roll-in Subjects: Prior to enrollment of the first randomized subject at each site, up to two roll-in subjects per operator (maximum 2 operators per site) who meet all eligibility criteria for the randomized trial may be enrolled. Roll-in subjects will receive PADN plus GDMT. Roll-in subjects will undergo all protocol-specified assessments. The sponsor will determine when each operator has achieved acceptable experience with the PADN procedure to advance to the randomized trial, after which no further roll-in patients will be enrolled. Operators who have performed ≥3 prior PADN procedures may not need to enroll a roll-in patient prior to beginning randomization. Randomized Subjects: Subjects with CpcPH due to LHD who meet all eligibility criteria will be randomized in a 1:1 ratio (stratified by investigational site and by core laboratory assessed LVEF \[≤40% vs \>40%\]) to one of the two treatment arms: 1. Intervention: PADN plus GDMT 2. Control: Placebo-procedure plus GDMT Subjects will undergo clinical follow-up at 1, 6, 12, 24 and 36 months. At 24 months, control subjects who have experienced a primary efficacy endpoint event and who still meet all eligibility criteria will be offered the opportunity to cross over to the PADN plus GDMT group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
750
In patients randomized to Intervention, a Contrast pulmonary artery (PA) angiography will be performed to identify the pulmonary artery bifurcation and measure the PA diameter. Once the anatomy is deemed suitable, a radiofrequency ablation catheter will be introduced into the ostium of the left PA and the distal bifurcation of the main PA. The catheter will be maneuvered within the PA to deliver energy circumferentially, ensuring tight electrode contact with the endovascular surface. Approximately three ablations will be performed at a target temperature of 50 °C (range 45-55 °C) for 120 seconds each at both the left PA ostium and the distal main PA bifurcation. All patients enrolled in this clinical study will following the Guideline-Directed Medical Therapy (GDMT)
In patients randomized to a placebo-procedure, a script will be followed for approximately 20 minutes to simulate the PADN procedure. All patients enrolled in this clinical study will following the Guideline-Directed Medical Therapy (GDMT)
Primary Efficacy Endpoint
Composite of Major Heart Failure Events (MHFE). Based on a time-to-first event analysis at 24-month follow-up evaluated when the last enrolled patient reaches 12-month follow-up: 1. Cardiovascular death; 2. Heart transplantation or durable left ventricular assist device (LVAD) implantation; 3.HF hospitalizations; 4. Outpatient worsening HF events
Time frame: Immediately after the randomization to last enrolled patient reaches 12-month follow-up
Primary Safety Endpoint
Composite of Device-related or Procedre-related Major Adverse Events (MAEs) in the treatment group compared with a performance goal
Time frame: 30-days
Cumulative incidence of Major Heart Failure Events
All the following events as following: 1. Cardiovascular death; 2.Heart transplantation or durable left ventricular assist device (LVAD) implantation; 3.HF hospitalizations ; 4.Outpatient worsening HF events
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
Outpatient worsening HF events
Number of outpatients requiring intravenous medication (inotropes, diuretics or vasodilators) due to worsening of heart failure
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
All cardiovascular hospitalizations
Number of patients with cardiovascular hospitalizations
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
N-terminal pro-B-type natriuretic peptide (NT-proBNP)
Changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline
Time frame: 6 months, 12 months, 24 months, and 36 months
6 minute walk distance(6MWD)
6 minute walk distance(6MWD) difference from baseline
Time frame: 6 months, 12 months, 24 months, and 36 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)
The KCCQ is a self-administered, questionnaire to provide a better description of quality of life in patients with heart failure. The overall summary score range from 0 to 100, higher score means higher quality of life. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score from baseline to 30 days and 6, 12, 24, and 36 months than baseline
Time frame: 6 months, 12 months, 24 months, and 36 months
durable left ventricular assist device (LVAD) implantation
durable left ventricular assist device (LVAD) implantation (time to first and all events, including recurrent events)
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
heart transplantation
number of heart transplantation (time to first event)
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
Durable LVAD implantation
number of durable LVAD implantation (time to first event)
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
Cardiovascular death
number of cardiovascular death
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
Atrial septostomy
number of atrial septostomy (time to first event)
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
HF hospitalizations
number of HF hospitalizations (time to first and all events, including recurrent events)
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
Atrial shunt placement
Number of atrial shunt placement for all the subjects (time to first event)
Time frame: 30days, 6 months, 12 months, 24 months, and 36 months
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