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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Pulmonary artery denervation
Sham procedure
Sponsored by
SoniVie Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Sham Comparator

    Arm Label

    Treatment group

    Sham control group

    Arm Description

    Pulmonary artery denervation with the TIVUS™ System will be performed immediately after the right heart catheterization and pulmonary artery angiography.

    A sham treatment of pulmonary artery denervation with the TIVUS™ System will be performed immediately after the right heart catheterization pulmonary artery angiography. The sham procedure will be identical to the denervation procedure, with the only exception that the procedure will use a sham setting on the control console.

    Outcomes

    Primary Outcome Measures

    6 minute walking distance (6MWD)
    Statistical difference in 6MWD between the treated group and the sham control group
    The rate of procedure and treatment related SAEs reported

    Secondary Outcome Measures

    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
    Difference between time to clinical worsening event between the treated group and the sham control group
    Difference between the number of clinical worsening events between the treated group and the sham control group
    The definition of clinical worsening events includes: all cause death, hospitalization for worsening PAH, lung/heart transplant, arterial septostomy, initiation of parenteral prostanoid therapy, change in dose and/or number of PAH specific medication. Each event will be counted as a single event and per each patient the total number of events will be recorded
    Difference between the treated group and the sham control group in resting mean right atrial pressure (mRAP)
    Difference between the treated group and the sham control group in resting mean pulmonary artery pressure (mPAP)
    Difference between the treated group and the sham control group in resting pulmonary vascular resistance (PVR)
    Difference between the treated group and the sham control group in resting cardiac index (CI)
    Difference between the treated group and the sham control group in Quality of Life (QOL) score using the SF36 questionnaire
    The SF36 is a 0-100 score, the lower the score is the lower the quality of life is, so that zero is equivalent to maximum disability and a score of 100 is equivalent to no disability at all
    Difference between the treated group and the sham control group of NT-pro-BNP levels
    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
    PAH patient's WHO functional class is a scale of 1 to 4 based on the symptoms patient experience when doing everyday activities, were Functional Class 1 and 2 are associated with limited effect on patient activity and lower risk status, and Functional Class 3 and 4 are associated with limited activity and higher risk status
    Percent of patients who improve or maintain their exercise tolerance (as measured by 6MWD and actigraphy)

    Full Information

    First Posted
    September 8, 2020
    Last Updated
    March 30, 2022
    Sponsor
    SoniVie Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04570228
    Brief Title
    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

    2. Study Status

    Record Verification Date
    March 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2023 (Anticipated)
    Primary Completion Date
    December 1, 2023 (Anticipated)
    Study Completion Date
    December 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    SoniVie Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    Yes
    Device Product Not Approved or Cleared by U.S. FDA
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pulmonary Arterial Hypertension

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Crossover Assignment
    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.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    205 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment group
    Arm Type
    Active Comparator
    Arm Description
    Pulmonary artery denervation with the TIVUS™ System will be performed immediately after the right heart catheterization and pulmonary artery angiography.
    Arm Title
    Sham control group
    Arm Type
    Sham Comparator
    Arm Description
    A sham treatment of pulmonary artery denervation with the TIVUS™ System will be performed immediately after the right heart catheterization pulmonary artery angiography. The sham procedure will be identical to the denervation procedure, with the only exception that the procedure will use a sham setting on the control console.
    Intervention Type
    Device
    Intervention Name(s)
    Pulmonary artery denervation
    Intervention Description
    The TIVUS system will be used for pulmonary artery denervation using non focused ultrasound
    Intervention Type
    Device
    Intervention Name(s)
    Sham procedure
    Intervention Description
    A sham procedure would be performed using the TIVUS system without delivering the non focused ultrasound
    Primary Outcome Measure Information:
    Title
    6 minute walking distance (6MWD)
    Description
    Statistical difference in 6MWD between the treated group and the sham control group
    Time Frame
    6 months
    Title
    The rate of procedure and treatment related SAEs reported
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    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
    Time Frame
    6 months
    Title
    Difference between time to clinical worsening event between the treated group and the sham control group
    Time Frame
    6 months
    Title
    Difference between the number of clinical worsening events between the treated group and the sham control group
    Description
    The definition of clinical worsening events includes: all cause death, hospitalization for worsening PAH, lung/heart transplant, arterial septostomy, initiation of parenteral prostanoid therapy, change in dose and/or number of PAH specific medication. Each event will be counted as a single event and per each patient the total number of events will be recorded
    Time Frame
    6 months
    Title
    Difference between the treated group and the sham control group in resting mean right atrial pressure (mRAP)
    Time Frame
    6 months
    Title
    Difference between the treated group and the sham control group in resting mean pulmonary artery pressure (mPAP)
    Time Frame
    6 months
    Title
    Difference between the treated group and the sham control group in resting pulmonary vascular resistance (PVR)
    Time Frame
    6 months
    Title
    Difference between the treated group and the sham control group in resting cardiac index (CI)
    Time Frame
    6 months
    Title
    Difference between the treated group and the sham control group in Quality of Life (QOL) score using the SF36 questionnaire
    Description
    The SF36 is a 0-100 score, the lower the score is the lower the quality of life is, so that zero is equivalent to maximum disability and a score of 100 is equivalent to no disability at all
    Time Frame
    6 months
    Title
    Difference between the treated group and the sham control group of NT-pro-BNP levels
    Time Frame
    6 months
    Title
    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
    Description
    PAH patient's WHO functional class is a scale of 1 to 4 based on the symptoms patient experience when doing everyday activities, were Functional Class 1 and 2 are associated with limited effect on patient activity and lower risk status, and Functional Class 3 and 4 are associated with limited activity and higher risk status
    Time Frame
    6 months
    Title
    Percent of patients who improve or maintain their exercise tolerance (as measured by 6MWD and actigraphy)
    Time Frame
    6 months
    Other Pre-specified Outcome Measures:
    Title
    Clinical change of pulmonary arterial hypertension condition defined by escalation of PAH specific drug therapy
    Description
    Change in the dose of medication
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by escalation of PAH specific drug therapy
    Description
    Change in the number of PAH specific medication
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by escalation of concomitant drug therapy
    Description
    Change in the number of concomitant medication
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by escalation of concomitant drug therapy
    Description
    Change in dose of a medication
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by change from baseline of ECG parameters demonstrating initiation or worsening of heart block
    Description
    Heart block is defined as long PR interval, wide or narrow QRS complex and/or QRS complex in various leads are oriented rightward and anteriorly. Heart block will be noted as either present or not present. Any change from baseline will be noted.
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by change from baseline of ECG parameters indicating initiation or worsening of arrhythmia
    Description
    Arrhythmia is defined when the P-P interval and/or R-R interval has differences of more than 10% and/or there are no visible P waves and/or irregularly irregular QRS complex is present. Arrhythmia will be noted as either present or not present. Any change from baseline will be noted.
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by change from baseline of ECG parameters indicating initiation or worsening of right ventricular hypertrophy (RVH)
    Description
    Right ventricular hypertrophy is when the following are present: right axis deviation > 90 degrees, tall R-waves in RV leads; deep S-waves in LV leads, slight increase in QRS duration and ST-T changes directed opposite to QRS direction (i.e., wide QRS/T angle). Right ventricular hypertrophy will be noted as either present or not present. Any change from baseline will be noted.
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by change from baseline of ECG parameters indicating initiation or worsening of axis deviation
    Description
    Axis deviation is present when QRS axis is greater than +90° or smaller than +30°. Axis deviation will be noted as either present or not present. Any change from baseline will be noted.
    Time Frame
    6, 12, 24, 36 month
    Title
    Change from baseline of 6MWD
    Time Frame
    12, 24, 36 month
    Title
    Change from baseline of NT-pro BNP levels
    Time Frame
    12, 24, 36 month
    Title
    Change from baseline of actigraphy measures as will be measured using an Actigraph Centrepoint Insight Activity monitor
    Time Frame
    12, 24, 36 month
    Title
    Change from baseline of Quality of Life (QOL) score using the SF36 questionnaire
    Description
    PAH patient's WHO functional class is a scale of 1 to 4 based on the symptoms patient experience when doing everyday activities, were Functional Class 1 and 2 are associated with limited effect on patient activity and lower risk status, and Functional Class 3 and 4 are associated with limited activity and higher risk status
    Time Frame
    12, 24, 36 month
    Title
    Survival or the cause of mortality
    Time Frame
    6, 12, 24, 36 month
    Title
    Amount of Hospitalizations events due to pulmonary arterial hypertension
    Time Frame
    6, 12, 24, 36 month
    Title
    Number of patients with clinical worsening of PAH condition resulting with interventional or surgical procedures, such as heart/lung transplant or atrial septostomy.
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by worsening of patients' WHO functional class
    Description
    PAH patient's WHO functional class is a scale of 1 to 4 based on the symptoms patient experience when doing everyday activities, were Functional Class 1 and 2 are associated with limited effect on patient activity and lower risk status, and Functional Class 3 and 4 are associated with limited activity and higher risk status
    Time Frame
    12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by escalation of concomitant drug therapy
    Description
    Change in the dose of medication
    Time Frame
    6, 12, 24, 36 month
    Title
    Clinical change of pulmonary arterial hypertension condition defined by escalation of concomitant drug therapy
    Description
    Change in the number of concomitant medications
    Time Frame
    6, 12, 24, 36 month

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Written informed consent to participate in the study obtained from the subject, according to local regulations, prior to initiation of any study mandated procedure. Male or female ≥ 18 years of age at the time of screening 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) Subject is on maximally tolerated medical therapy for PAH, as determined by his PAH physician 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) Subject is able to tolerate IV contrast used for the angiograms during treatment Subject is WHO functional class II or III Exclusion Criteria: Subject is treated with parenteral prostanoids and has not been on a stable dose for at least 3 months Subjects with portal-pulmonary hypertension, Group 2, 3 and 4 PH Pregnant women or women planning a pregnancy within 12 months of study enrolment Subject with significant co-morbid conditions which, at the discretion of the PI, are deemed to prohibit study entry Subject 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) Subject with pulmonary artery anatomy that precludes treatment with the TIVUS System Subject who has experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident in the previous 6 months Subject experiencing a current episode of acute decompensated heart failure Subject who has cardiac pacemakers/ICD/CRT-D that were implanted fewer than three months prior to enrollment. Subject who has implantable Cardiomems device, or other implanted device that might be contraindicated for therapeutic ultrasound energy.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Dalit Shav, PhD
    Phone
    +19784600773
    Email
    info@sonivie.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Charles S Carignan, MD
    Phone
    +19784600773
    Email
    info@sonivie.com

    12. IPD Sharing Statement

    Learn more about this trial

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

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