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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
205
The TIVUS system will be used for pulmonary artery denervation using non focused ultrasound
A sham procedure would be performed using the TIVUS system without delivering the non focused ultrasound
6 minute walking distance (6MWD)
Statistical difference in 6MWD between the treated group and the sham control group
Time frame: 6 months
The rate of procedure and treatment related SAEs reported
Time frame: 12 months
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
Difference between time to clinical worsening event between the treated group and the sham control group
Time frame: 6 months
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
Time frame: 6 months
Difference between the treated group and the sham control group in resting mean right atrial pressure (mRAP)
Time frame: 6 months
Difference between the treated group and the sham control group in resting mean pulmonary artery pressure (mPAP)
Time frame: 6 months
Difference between the treated group and the sham control group in resting pulmonary vascular resistance (PVR)
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Time frame: 6 months
Difference between the treated group and the sham control group in resting cardiac index (CI)
Time frame: 6 months
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
Time frame: 6 months
Difference between the treated group and the sham control group of NT-pro-BNP levels
Time frame: 6 months
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
Time frame: 6 months
Percent of patients who improve or maintain their exercise tolerance (as measured by 6MWD and actigraphy)
Time frame: 6 months