TROPHY PAH Pivotal Study - TReatment of Pulmonary HYpertension for PAH Pivotal Study

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

Theis is a prospective, multicenter, blinded, randomized sham controlled pivotal clinical trial with a crossover at 6M, to assess the safety and effectiveness of pulmonary artery denervation with the TIVUS™ System in subjects with PAH. The study will assess improved and/or maintained exercise tolerance in patients with PAH through the analysis of exercise tolerance, hemodynamic changes, clinical worsening and the quality of life who got treated by the TIVUS system.

Inclusion Criteria:

1. Written informed consent to participate in the study obtained from the subject, according to local regulations, prior to initiation of any study mandated procedure.

2. Male or female ≥ 18 years of age at the time of screening

3. Subject with known pulmonary arterial hypertension (PAH), which has been diagnosed as idiopathic PAH, connective tissue disease PAH, anorexigen induced, familial PAH or corrected congenital heart defects more than 1 year prior to enrollment, confirmed by right heart catheterization 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 (240 dyne*s/cm^5)

4. Subject is on maximally tolerated medical therapy for PAH, as determined by his PAH physician

5. Subject 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)

6. Subject is able to tolerate IV contrast used for the angiograms during treatment

7. Subject is WHO functional class II or III

Exclusion Criteria:

1. Subject is treated with parenteral prostanoids and has not been on a stable dose for at least 3 months
2. Subjects with portal-pulmonary hypertension, Group 2, 3 and 4 PH
3. Pregnant women or women planning a pregnancy within 12 months of study enrolment
4. Subject with significant co-morbid conditions which, at the discretion of the PI, are deemed to prohibit study entry
5. Subject with life expectancy of less than a year
6. Concurrent enrollment in another device or drug trial except for observational studies (unless specifically approved by the sponsor)
7. Subject with pulmonary artery anatomy that precludes treatment with the TIVUS System
8. Subject who has experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident in the previous 6 months
9. Subject experiencing a current episode of acute decompensated heart failure
10. Subject who has cardiac pacemakers/ICD/CRT-D that were implanted fewer than three months prior to enrollment.
11. Subject who has implantable Cardiomems device, or other implanted device that might be contraindicated for therapeutic ultrasound energy.