TReatment of Pulmonary Hypertension Group II Study

Study Overview
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Brief Summary
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The objective of this study is to assess the safety and initial effectiveness of the TIVUS™ System when used for pulmonary artery denervation in group II PH patients through change in clinical parameters including hemodynamics, exercise tolerance, and quality of life. This is a prospective, multi-center, non-randomized, open-label clinical trail. The study will be conducted in up to 3 centers and will recruit up to 15 patients diagnosed with pulmonary hypertension due to left heart disease that demonstrate combined pre and post capillary involvement with PVR>3 wood units.

Official Title
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Clinical Evaluation of the Therapeutic Intra-Vascular Ultrasound (TIVUS™) System for Pulmonary Artery Denervation in Patients With Pulmonary Hypertension Due to Left Heart Disease

Conditions
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Pulmonary Hypertension (PH) Due to Left Heart Disease

Intervention / Treatment
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* Device: Pulmonary Denervation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent to participate in the study obtained from the patient, according to local regulations, prior to initiation of any study mandated procedure. Male or female, ≥ 18 years of age at the time of screening Patient with known pulmonary hypertension (PH) due to left heart disease (WHO Group II) diagnosed as either HFpEF or HFrEF at chronic state receiving stable guideline directed medical therapy. Combined post-capillary and precapillary pulmonary hypertension diagnosis confirmed by hemodynamic evaluation performed prior to screening or during baseline (Eligibility II visit) procedure Patient with a current diagnosis of NYHA functional class II/III Patient with eGFR levels of ≥ 30 ml/min/1.73m2or serum creatinine levels of ˂ 150μmol/l Exclusion Criteria: 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 experiencing a current episode of acute decompensated heart failure Patient who has cardiac pacemakers/ICD/CRT-D that were implanted fewer than three months prior to enrolment. Patient who has implantable Cardiomems device, neurostimulators or drug infusion devices, regardless of implant date.

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Pulmonary Denervation|Pulmonary Denervation (PDN) using the TIVUS™ System will be performed in patient suffering from pulmonary 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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedural related Adverse Events (complications) at up to 30 days post procedure | Procedural related Adverse Events (complications) at up to 30 days post procedure including pulmonary artery perforation/dissection, acute thrombus formation in the pulmonary artery, pulmonary artery aneurysm, vascular stenosis, hemoptysis, all cause PH related as well as procedural related death. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cardiopulmonary exercise test | Changes in cardiopulmonary exercise test (CPET) results (Peak VO2, VE/VCO2 slope, VO2 at anaerobic threshold, peak workload) from baseline | 4 month | 
| Change in resting mean right atrial pressure | Change in resting mean atrial pressure (mRAP) from baseline | 4 month | 
| Changes in 6MWD from baseline | Changes in 6MWD from baseline | 4 month | 
| Changes in Echocardiography parameters | Changes in Echocardiography parameters including Right Ventricular function from baseline | 4 month | 
| Change in NT-BNP levels | Change in NT-BNP levels from baseline | 4 month | 
| Procedure related and PH worsening adverse events | Procedure related and PH worsening adverse events and all cause death up to 12 months will be recorded, and serious adverse events will be reported in accordance with regulatory requirements. | 12 month | 
| Change in exercise mean right atrial pressure | Change in exercise mean right atrial pressure (mRAP) from baseline | 4 month | 
| Change in exercise mean pulmonary artery pressure | Change in exercise mean pulmonary artery pressure (mPAP) from baseline | 4 month | 
| Change in exercise pulmonary vascular resistance | Change in exercise pulmonary vascular resistance (PVR) from baseline | 4 month | 
| Change in exercise cardiac index | Change in exercise cardiac index (CI) from baseline | 4 month | 
| Change in resting mean pulmonary artery pressure | Change in resting mean pulmonary artery pressure (mPAP) from baseline | 4 month | 
| Change in resting pulmonary vascular resistance | Change in resting pulmonary vascular resistance (PVR) from baseline | 4 month | 
| Change in resting cardiac index | Change in resting cardiac index (CI) from baseline | 4 month |