Clinical trial NCT04570228: TROPHY PAH Pivotal Study - TReatment of Pulmonary HYpertension for PAH Pivotal Study
Official title: Clinical Evaluation of the Therapeutic Intra-Vascular Ultrasound (TIVUS™) System for Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: SoniVie Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-30
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Subjects will be randomized 2:1 with a sham controlled arm, with subjects and all follow up staff blinded to the subject treatment. Subjects will be unblinded at 6M, and sham control group will be offered treatment at this time if they meet the inclusion/ exclusion criteria. The primary effectiveness endpoint is measured at 6 months. The safety endpoint for blinded patients is at 6 months, and for treated patients again at 12 months.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 6 minute walking distance (6MWD)
timeFrame: 6 months
measure: The rate of procedure and treatment related SAEs reported
timeFrame: 12 months
Secondary outcomes:
measure: Statistical difference between the treated group and the sham control group in exercise tolerance as measured using the change in activity parameters using the Actigraph Centrepoint watch
timeFrame: 6 months
measure: Difference between time to clinical worsening event between the treated group and the sham control group
timeFrame: 6 months
measure: Difference between the number of clinical worsening events between the treated group and the sham control group
timeFrame: 6 months
measure: Difference between the treated group and the sham control group in resting mean right atrial pressure (mRAP)
timeFrame: 6 months
measure: Difference between the treated group and the sham control group in resting mean pulmonary artery pressure (mPAP)
timeFrame: 6 months
measure: Difference between the treated group and the sham control group in resting pulmonary vascular resistance (PVR)
timeFrame: 6 months
measure: Difference between the treated group and the sham control group in resting cardiac index (CI)
timeFrame: 6 months
measure: Difference between the treated group and the sham control group in Quality of Life (QOL) score using the SF36 questionnaire
timeFrame: 6 months
measure: Difference between the treated group and the sham control group of NT-pro-BNP levels
timeFrame: 6 months
measure: Difference between the treated group and the sham control group in patients' clinical pulmonary arterial hypertension condition defined by worsening of World Health Organization (WHO) functional class
timeFrame: 6 months
measure: Percent of patients who improve or maintain their exercise tolerance (as measured by 6MWD and actigraphy)
timeFrame: 6 months
Other outcomes:
measure: Clinical change of pulmonary arterial hypertension condition defined by escalation of PAH specific drug therapy
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by escalation of PAH specific drug therapy
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by escalation of concomitant drug therapy
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by escalation of concomitant drug therapy
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by change from baseline of ECG parameters demonstrating initiation or worsening of heart block
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by change from baseline of ECG parameters indicating initiation or worsening of arrhythmia
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by change from baseline of ECG parameters indicating initiation or worsening of right ventricular hypertrophy (RVH)
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by change from baseline of ECG parameters indicating initiation or worsening of axis deviation
timeFrame: 6, 12, 24, 36 month
measure: Change from baseline of 6MWD
timeFrame: 12, 24, 36 month
measure: Change from baseline of NT-pro BNP levels
timeFrame: 12, 24, 36 month
measure: Change from baseline of actigraphy measures as will be measured using an Actigraph Centrepoint Insight Activity monitor
timeFrame: 12, 24, 36 month
measure: Change from baseline of Quality of Life (QOL) score using the SF36 questionnaire
timeFrame: 12, 24, 36 month
measure: Survival or the cause of mortality
timeFrame: 6, 12, 24, 36 month
measure: Amount of Hospitalizations events due to pulmonary arterial hypertension
timeFrame: 6, 12, 24, 36 month
measure: Number of patients with clinical worsening of PAH condition resulting with interventional or surgical procedures, such as heart/lung transplant or atrial septostomy.
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by worsening of patients' WHO functional class
timeFrame: 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by escalation of concomitant drug therapy
timeFrame: 6, 12, 24, 36 month
measure: Clinical change of pulmonary arterial hypertension condition defined by escalation of concomitant drug therapy
timeFrame: 6, 12, 24, 36 month
Locations:
Study officials:
References: