PNEUMOSTEM® for Improving Respiratory Outcomes in Very Premature Infants Diagnosed With Early Pulmonary Arterial Hypertension

Time from PNEUMOSTEM administration to complete reversal of intracardiac shunt from right-to-left to complete left-to-right direction, as assessed by echocardiography.

Time from PNEUMOSTEM administration to resolution of flattened interventricular septum or disappearance of D-shaped left ventricle at end-systole, as assessed by echocardiography.

Change in duration of pulmonary hypertension medication use by medication type following PNEUMOSTEM administration compared to standard care. Duration will be measured in days for each medication type used to treat pulmonary hypertension.

Change in total duration of mechalical ventilator use following PNEUMOSTEM andministration compared to standard care. Duration will be measured in days from initiation to discontinuation of mechanical ventilation.

Change in total duration of supplemental oxygen use following PNEUMOSTEM administration compared to standard care. Duration will be measured in days from initiation to discontinuation of oxygen therapy.

Inicidence of bronchopulmonary dysplasia assessed according to standard diagnostic criteria(requirement for supplemental oxygen at 28 days of postnatal age and/or at 36 weeks postmenstrual age).

Severity assessment of bronchopulmonary dysplasia categorized according to the definition of NIHCD 2001, NICHD 2018 and JENSEN 2019.

Incidence of retinopathy of prematurity assessed by ophthalmologic examination according to the International Classification of Retinopathy of Prematurity.

Severity assessment of retinopathy of prematurity including staging(Stage 1~5), zone(Zone I, II, or III), and presence of pulse disease. Assessment of treatment requirements including lase photocoagulation, anti-VEGF injection, or surgical intervention.

Time point of early detection of brain injury or neurodevelopmental abnormalities on brain MRI performed at postmenstrual age 36~40 weeks. Brain injuries assessed include intraventricular hemorrhage, periventricular leukomalacia, and other structural abnormalities.

Incidence of respiratory-related moratlity confirmed by medical records and information survey. Respiratory-related mortality is defined as death primarily attributed to respiratory failure, pulmonary hypertension, or complications of bronchopulmonary dysplasia.

Postnatal age(in days) at which respiratory-related death occurs in participants who experience this outcome. Time will be measured from PNEUMOSTEM administration to the date of death.

Incidence of adverse events graded according to the latest version of Common Terminology Criteria for Adverse Events(CTCAE). All adverse events will be recorded and categorized by system organ class and severity grade.

Change in body weight from baseline(PNEUMOSTEM administration day) measured in grams.

Change in head circumference from baseline(PNEUMOSTEM administration day) measured in centimeters.

Incidence of clinically significant abnormal findings on physical examination of skin and head/neck regions.

Incidence of clinically significant abnormal findings on physical examination of heart and lung systems.

Incidence of clinically significant abnormal findings on physical examination of abdomen and genitalia.

Incidence of clinically significant abnormal findings on physical examination of nervous system and musculoskeletal systems.

Change in systolic and diastolic blood pressure from baseline(PNEUMOSTEM administration day) measured in mmHg.

Change in body temperature from baseline(PNEUMOSTEM administration day) measured in degrees celsius.

Change in heart rate(pulse) from baseline(PNEUMOSTEM administration day) measured in beats per minute.

Change in respiratory rate from baseline(PNEUMOSTEM administration day) measured in breaths per minute.

Change in oxygen saturation(SpO2) from baseline(PNEUMOSTEM administration day) measure as percentage.

Incidence of clinically significant abnormal hematology laboratory values including white blood cell count(WBC), red blood cell count(RBC), hemoglobin(Hb), hematocrit(Hct), and platelet count(PLT).

Incidence of clinically significant abnormal blood chemistry values including C-reactive protein(CRP) and other relevant biochemical markers.

Incidence of clinically significant abnormal findings on continuous electrocardiography monitoring including arrhythmias, conduction abnormalities, or other cardiac electrical disturbances.

Incidence of infectious disease identified by blood and tracheal aspirate(TTA) cultures with component analysis and pathogen identification.

Incidence of clinically significant abnormal blood gas analysis results for assessment of respiratory and metabolic status including PH, PaO2, PaCO2 and base excess.

Incidence of clinically significant abnormal findings on chest radiography including evaluation for pleural effusion, pneumothorax, infiltrates, or other pulmonary abnormalities.