Back to resultsTROPHY 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
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
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.
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
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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