TReatment Of Pulmonary HYpertension 1-US Study

Study Overview
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Brief Summary
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The objective of this study is to assess the safety, performance and initial effectiveness of the TIVUS™ System when used for pulmonary artery denervation through subjective and objective change in clinical parameters and haemodynamic evaluation. This is a prospective, multi-center, non-randomized, open-label clinical trail. The study will be conducted in up to 4 centers and will recruit up to 15 patients diagnosed with PAH, functional class III who have stable PAH on a stable drug regimen of two pulmonary arterial hypertension specific medications.

Official Title
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Clinical Evaluation of the Therapeutic Intra-Vascular Ultrasound (TIVUS™) System for Pulmonary Artery Denervation (PDN) in Patients With Pulmonary Hypertension - US

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Device: Therapeutic Intra-Vascular UltraSound (TIVUS™) System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with known pulmonary arterial hypertension (PAH), diagnosed as idiopathic PAH, connective tissue disease PAH, Anorexogen induced or Heritable PAH PAH diagnosis confirmed by hemodynamic evaluation performed prior to screening and showing all of the following: Mean pulmonary artery pressure (mPAP) ≥25 mmHg at rest; Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤15 mmHg; Pulmonary vascular resistance (PVR) at rest >3 Wood units; Not meeting the criteria for a positive vasodilator response (fall in mPAP ≥ 10 mmHg to ≤ 40 mmHg). Patient with a current diagnosis of WHO functional class III Patient taking two pulmonary arterial hypertension specific medications other than parenteral prostanoids Patient is adhering to a stable drug regimen (i.e., with no changes of dose or medication for a minimum of 3 months prior to enrollment) Patient with eGFR levels of ≥ 30 ml/min/1.73m2or serum creatinine levels of ˂ 150µmol/l Exclusion Criteria: Patients who are treated with parenteral prostanoids Pregnant women or women planning a pregnancy within 12 months of study enrolment Patient with significant co-morbid condition(s) which, at the discretion of the PI, are deemed to prohibit study entry Patient with life expectancy of less than a year Concurrent enrollment in another device or drug trial except for observational studies (unless specifically approved by the sponsor) Patient with pulmonary artery anatomy that precludes treatment Patient with moderate to severe pulmonary artery stenosis Patient with any pulmonary artery aneurysm Patient who has experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident in the previous 6 months Patient who has implantable cardiac pacemakers, ICDs, neurostimulators, or drug infusion devices Patients who are unable to undergo an MRI scan

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pulmonary Denervation<br>Pulmonary Denervation (PDN) using the TIVUS™ System will be performed in patient suffering from pulmonary arterial hypertension after completion of screening and eligibility phase, The procedure will be performed during right heart catheterisation. Safety and effectiveness of the PDN treatment will be assessed during one year follow up. | Device: Therapeutic Intra-Vascular UltraSound (TIVUS™) System<br>* The TIVUS™ System generates high intensity, non-focused ultrasonic energy that is delivered through the wall of the pulmonary artery to achieve local nerve deactivation. Denervation in the pulmonary arteries (PDN) would be performed during right heart catheterization. The PDN procedure would be attempted in the main, right and left pulmonary arteries, close to the main bifurcation.<br>* Other names: TIVUS™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of all procedural related adverse event as assessed by the CEC | Procedural related Adverse Events | 1 month | 
| Amount of treatment related adverse event as assessed by the CEC | All treatment related adverse events | 12 month | 
| Number of patient with PAH worsening and all cause death events | PAH related adverse events and all cause death | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical effectiveness | Changes from baseline of mean pulmonary arterial pressure (mPAP) | 6 months | 
| Clinical effectiveness | Changes from baseline of pulmonary vascular resistance (PVR) | 6 months | 
| Clinical effectiveness | Changes from baseline of 6 minute walking distance (6MWD) | 6 months | 
| Clinical effectiveness | Changes from baseline of quality of life questionaire | 6 months | 
| Clinical effectiveness | NT-pro-BNP levels | 1, 6 and 12 months | 
| Clinical efffectivness | Change from baseline in Right Ventricular (RV) function as assesed by MRI | 6 months | 
| Clinical efffectivness | Change from baseline in Right Ventricular (RV) function as assesed by Echocardiography | 6 months |