In this study, pulmonary hypertension (PH) is defined as systolic pulmonary arterial pressure (sPAP) ≥ 38 mmHg by 2-D echocardiogram with Doppler.
NO cylinder concentrations (4880 ppm) at a dose of 30 mcg/kg Ideal Body Weight (IBW)/hr (INOpulse setting of 30 mcg/kg IBW/hr) will be administered.
During the screening visit all the inclusion and exclusion criteria will be checked. Eligible patients will return to the site for visit 1. During visit 1 baseline HRCT scans with contrast agent will be obtained at Functional Residual Capacity (FRC) and Total Lung Capacity (TLC). Before the scans are taken a urine pregnancy test will be obtained in female patients with childbearing potential. A retest of the eGFR CKD-EPI value should also be performed before administering the contrast agent, if there is a clinical indication according to the investigator. The treatment will be started after all baseline assessments (physical examination, patency of nares, eGFR CKD-EPI determination, urine pregnancy test, HRCT scans, vital signs including oxygen saturation measurement, Electrocardiogram (ECG), Arterial Blood Gas (ABG), MetHb, 6-minutes walking distance (6MWD) (before and after the 6 MWD a Borg Category Ratio (Borg CR10) leg fatigue and dyspnea scale will be executed and during the 6MWD the oxygen saturation will be measured), PRO, spirometry). A second TLC and FRC scan with contrast agent during the iNO treatment will be taken. The scans will be taken whilst the patient is under iNO treatment for at least 20 minutes on the iNOpulse specific cannula. After the scans taken during the iNO treatment are performed some of the baseline assessments will be repeated whilst the patient is on iNO treatment (vital signs including oxygen saturation measurement, ABG, MetHb, 6MWD (before and after the 6 MWD a Borg CR10 leg fatigue and dyspnea scale will be executed and during the 6MWD the oxygen saturation will be measured), PRO, spirometry). During visit 1 the investigator will discontinue iNO to assess if rebound pulmonary hypertension occurs. In the first 2 patients, iNO therapy will be discontinued while 2D echo is performed to assess sPAP. Furthermore, NIBP, HR, SpO2 will be measured. In the remaining patients the following additional safety assessments (NIBP, HR, SpO2) will be performed while the patient is discontinued at least 20 minutes of iNO. If the investigator considers it is safe to restart the iNO-therapy, the patient will start chronic iNO treatment. After the results of the safety assessments of the 2 first patients are collected a safety meeting will be held to evaluate the results. Depending on the results, the additional 2D echo may be performed in additional patients. Subjects will be contacted via telephone or e-mail ± 24 hours after visit 1, for assessment of vital status, concomitant medications and the occurrence of new AEs or worsening of previously existing recorded AEs and PRO (= visit 2). After 2 weeks of treatment of iNO with a dosage of 30 mcg/kg IBW/hr during at least 12 hours a day patients will be asked to return to the site for visit 3. During that visit following measurements will be performed: patency of nares will be checked, vital signs including oxygen saturation measurement, MetHb, 6MWD (with Borg CR10 leg fatigue and dyspnea scale and oxygen saturation measurement), PRO and AE assessment. After 4 weeks treatment visit 4 will be conducted. 2D - echocardiogram with Doppler (immediately after the 2D - echocardiogram with Doppler NIBP, HR, SpO2 will be measured) and HRCT scans with contrast agent under iNO pulse will be taken. Before the scans are taken an urine pregnancy test will be obtained, if applicable. A retest of the eGFR CKD-EPI value should also be performed before administering the contrast agent, if there is a clinical indication according to the investigator. Spirometry assessments will be performed, patency of nares, ECG, ABG, MetHb, 6MWD (with Borg CR10 fatigue and dyspnea scale and oxygen saturation measurement), PRO will be assessed. After all assessments are completed, iNO will be discontinued. Twenty minutes after discontinuation of iNO-therapy, spirometry, PRO, MetHb, 6MWD (before and after the 6 MWD a Borg CR10 leg fatigue and dyspnea scale will be executed and during the 6MWD the oxygen saturation will be measured) and 2D-echocardiogram with Doppler measurements measurement will be repeated. Vital signs with oxygen saturation will be measured immediately after the 2D-echocardiogram with Doppler. After all the assessments the patient is placed back on his/her prescribed dose of LTOT using their usual cannula. The patient will be assessed for any signs of acute withdrawal. Therefore vital signs including oxygen saturation will be measured.
At visit 5, two weeks after discontinuation of iNO treatment repeat vital signs with oxygen saturation measurement, physical examination, patency of nares, spirometry, 2D-echocardiogram with Doppler (immediately after the 2D - echocardiogram with Doppler NIBP, HR, SpO2 will be measured), ABG, MetHb, 6MWD(with Borg CR10 leg fatigue and dyspnea scale and oxygen saturation measurement), and PRO will be performed. If applicable a last urine pregnancy test will be executed to make sure no pregnancy occurred during the study. If there are no follow-up actions for a patient at this visit, it will be considered as a completion of study participation / end of study for that particular patient.
