TReatment Of Pulmonary HYpertension 1 Study (TROPHY)

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

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 5 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 (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Hôpital Erasme
• Israel
  • Rehovot, Israel
    • Kaplan Hospital
• United Kingdom
  • London, United Kingdom
    • Hammersmith Hospital, Imperial College Healthcare NHS Trust
  • Sheffield, United Kingdom
    • Royal Hallamshire Hospital,

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient with known pulmonary arterial hypertension (PAH), which has been diagnosed as idiopathic PAH, connective tissue disease PAH, anorexigen induced or familial 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 should be on 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:

• Patient who are treated with parenteral prostanoids
• Pregnant women or women planning a pregnancy within 12 months of study enrolment
• Patient with significant co-morbid conditions 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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation of the PDN procedure (Procedural related Adverse Events)	Procedural related Adverse Events	1 month
Safety evaluation of the PDN procedure (PAH related adverse events and all cause death)	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)	4 months
Clinical effectiveness	Changes from baseline of pulmonary vascular resistance (PVR)	4 months
Clinical effectiveness	Changes from baseline of 6 minute walking distance (6MWD)	4 months
Clinical effectiveness	Changes from baseline of quality of life questionaire	4 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	Changes from baseline of Nt-pro-BNP	12 Months
Observational Variables - Long term surveillance	Clinical change of pulmonary arterial hypertension condition defined by a. Survival or the cause of mortality; b. Hospitalization due to pulmonary arterial hypertension; c. Intervention or surgical procedures; d. Worsening of WHO functional class and/or e. Escalation of drug therapy	3 years

Collaborators and Investigators

• Sponsor: SoniVie Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): October 1, 2018
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: July 29, 2015
• First Submitted That Met QC Criteria: August 3, 2015
• First Posted (Estimate): August 6, 2015

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: March 1, 2021

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