TReatment Of Pulmonary HYpertension 1-US Study (TROPHY 1-US)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Device: Therapeutic Intra-Vascular UltraSound (TIVUS™) System

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • UC San Diego Health
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center/NewYork Presbyterian Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestren Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pulmonary Denervation; 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; 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.; Other Names: TIVUS™

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observational Variables	Changes from baseline of mean pulmonary arterial pressure (mPAP)	12 Months
Observational Variables	Changes from baseline of pulmonary vascular resistance (PVR)	12 Months
Observational Variables	Changes from baseline of 6 minute walking distance (6MWD)	12 Months
Observational Variables	Changes from baseline of quality of life questionaire	12 Months
Observational Variables - Long term surveillance	Clinical change of pulmonary arterial hypertension condition defined by patient survival or cause of mortality	2, 3, 4 and 5 years
Observational Variables - Long term surveillance	Clinical change of pulmonary arterial hypertension condition defined by hospitalization due to pulmonary arterial hypertension	2, 3, 4 and 5 years
Observational Variables - Long term surveillance	Clinical change of pulmonary arterial hypertension condition defined by any intervention or surgical procedures the patient did	2, 3, 4 and 5 years
Observational Variables - Long term surveillance	Clinical change of pulmonary arterial hypertension condition defined by worsening of WHO functional class	2, 3, 4 and 5 years
Observational Variables - Long term surveillance	Clinical change of pulmonary arterial hypertension condition defined by escalation of drug therapy	2, 3, 4 and 5 years
Observational Variables	Echocardiography parameters	12 month

Collaborators and Investigators

• Sponsor: SoniVie Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): April 20, 2019
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: July 10, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (Estimated): July 18, 2016

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: CLNS01-001 USA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes