PNEUMOSTEM® for Improving Respiratory Outcomes in Very Premature Infants Diagnosed With Early Pulmonary Arterial Hypertension (REVIVE-PH)

A Clinical Study of Advanced Regenerative Medicine to Evaluate the Safety and Potential Efficacy of PNEUMOSTEM® for Improving Respiratory Outcomes in Very Premature Infants Diagnosed With Early Pulmonary Arterial Hypertension

The goal of this clinical trial is to evaluate the safety and potential efficacy of PNEUMOSTEM® for improving respiratory outcomes in very premature infants diagnosed with Early Pulmonary Arterial Hypertension. The main questions it aims to answer are:

• In very premature infants diagnosed with early pulmonary arterial hypertension, will a single intratracheal administration of PNEUMOSTEM®(Allogeneic umbilical cord blood-derived mesenchymal stem cells) result in improvement of pulmonary arterial hypertension based on echocardiographic assessment?
• In very premature infants diagnosed with early pulmonary arterial hypertension who show improvement of pulmonary arterial hypertension based on echocardiographic assessment following a single intratracheal administration of PNEUMOSTEM®(Allogeneic umbilical cord blood-derived mesenchymal stem cells), at what time point does this improvement occur?

Participants will:

• Single intratracheal dose of PNEUMOSTEM® at 2.0 x 10,000,000 cells/kg
• Acute adverse event monitoring: 24 hours post-administration for safety assessment
• Follow- up time points: Day 1(Baseline, PNEUMOSTEM® administration), Day 2, Week 1, Week 2, Postnatal Day 28, PMA 36~40 weeks

Study Overview

• Status: Not yet recruiting
• Conditions: Premature Infants; Pulmonary Arterial Hypertension (PAH)
• Intervention / Treatment: Biological: PNEUMOSTEM®

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: So Yoon Ahn, M.D, Ph.D; Phone Number: +82-10-4038-0460; Email: yoon.ahn.neo@gmail.com

Study Locations

• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center, 81, Irwon-ro, Gangnam-gu, Seoul, Republic of Korea
    • Contact: Danbi Kim; Phone Number: +82-10-4601-9956; Email: danbi03.kim@samsung.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Premature infants within 2 weeks of birth with a gestational age of 28 weeks or less or birth weight of less than 1,250g who require continuous invasive mechanical ventilation

2. When diagnosed with early pulmonary arterial hypertension satisfying condition ① or ② up to 14 days after birth:

   • When on or more of the following abnormal findings are present on echocardiography performed between 4 and 14 days after birth (findings at 1-3 days after birth correspond to early neonatal transition):

     1. Sytemic or suprasystemic pulmonary artery pressure >40mmHg(based on peak Doppler velocity of tricuspid regurgitation)
     2. Right-to-left or bidirectional shunt through patent ductus arteriosus, foramen ovale, or atrial septal defect
     3. Flattened interventricular septum or D-shaped left ventricle at end systole ② When receiving nitric oxide(NO) inhalation therapy for persistent pulmonary hypertension of the newborn(PPHN) within 3 days after birth

Exclusion Criteria:

1. Those witth cyanotic congenital heart defects or acyanotic congenital heart defects causing heart failure, excluding patent ductus arteriosus in premature infatns
2. Those with severe pulmonary malformations such as congenital diaphragmatic hernia or congenital cystic lung disease
3. Those who underwent surgery within 72 hours before or after administration of the investigational cell product, or those for whom surgery is anticipated
4. Those who received surfactant within 24 hours prior to administration of the investigattional cell product
5. Those with chromosomal abnormalities accompanied by severe malformations(such as Edwards syndrome, Patau syndrome, Down syndrome, etc.) and severe congenital malformations(such as hydrocephalus, encephalocele, etc.)
6. Those with severe congenital infectious diseases(such as herpes, toxoplasmosis, rubella, syphilis, AIDS, etc.)
7. Those with severe sepsis or shock due to active infection not adequately treated with antibiotics
8. Those who have a history of participation in other advanced regenerative medicine clinical studies or clinical trials
9. Others deemed inappropriate by tthe investigator to participate in this advanced regenerative medicine clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PNEUMOSTEM® treatment arm; PNEUMOSTEM® will be administered intratracheally as a single dose of 2.0x10,000,000 cells/kg on Day 1.	Biological: PNEUMOSTEM®; PNEUMOSTEM® will be administered intratracheally as a single dose of 2.0x10000000 cells/kg on Day 1.; Other Names: Cell therapy product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time point(week) of complete reversal of cardiac shunt direction	Time from PNEUMOSTEM administration to complete reversal of intracardiac shunt from right-to-left to complete left-to-right direction, as assessed by echocardiography.	Biweekly from day after PNEUMOSTEM administration until postnatal day 28
Time to normalization of ventricular septal configuration	Time from PNEUMOSTEM administration to resolution of flattened interventricular septum or disappearance of D-shaped left ventricle at end-systole, as assessed by echocardiography.	Once between postnatal day 28 and PMA 36~40 weeks
Change in duration of pulmonary hypertension medication use	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.	Daily on PNEUMOSTEM administration day and the next day
Change in duration of mechanical ventilation	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.	Weekly at week 1 and week 2 after PNEUMOSTEM administration
Change in duration of supplemental oxygen therapy.	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.	Weekly at week 1 and week 2 after PNEUMOSTEM administration
Incidence of Bronchopulmonary Dysplasia(BPD)	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).	At postnatal day 28 and at between PMA 36~40 weeks
Severity of Bronchopulmonary Dysplasia(BPD)	Severity assessment of bronchopulmonary dysplasia categorized according to the definition of NIHCD 2001, NICHD 2018 and JENSEN 2019.	At postnatal day 28 and at between PMA 36~40 weeks
Incidence of Retinopathy of Prematurity(ROP)	Incidence of retinopathy of prematurity assessed by ophthalmologic examination according to the International Classification of Retinopathy of Prematurity.	Once at between PMA 36~40 weeks
Severity of Retinopathy of Prematurity(ROP)	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.	Once at between PMA 36~40 weeks
Time point of brain injury ditection on Brain MRI	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.	Once at between PMA 36~40 weeks
Incidence of Respiratory-related mortality	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.	From PNEUMOSTEM administration to PMA 36~40 weeks
Tiem point of respiratory-related mortality	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.	From PNEUMOSTEM administration to PMA 36~40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events Assessed by latest version of CTCAE	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.	From PNEUMOSTEM administration to PMA 36~40 weeks
Change in anthropometric measurements - Weight	Change in body weight from baseline(PNEUMOSTEM administration day) measured in grams.	From PNEUMOSTEM administration to PMA 36~40 weeks
Change in anthropometric measurements - Head Circumference	Change in head circumference from baseline(PNEUMOSTEM administration day) measured in centimeters.	From PNEUMOSTEM administration to PMA 36~40 weeks
Abnormal findings on physical examination - Skin and Head/Neck	Incidence of clinically significant abnormal findings on physical examination of skin and head/neck regions.	From PNEUMOSTEM administration to PMA 36~40 weeks
Abnormal findings on physical examination - Cardiovascular and Respiratory systems	Incidence of clinically significant abnormal findings on physical examination of heart and lung systems.	From PNEUMOSTEM administration to PMA 36~40 weeks
Abnormal findings on physical examination - Abdomen and Genitalia	Incidence of clinically significant abnormal findings on physical examination of abdomen and genitalia.	From PNEUMOSTEM administration to PMA 36~40 weeks
Abnormal findings on physical examination - Nervous and Musculoskeletal systems	Incidence of clinically significant abnormal findings on physical examination of nervous system and musculoskeletal systems.	From PNEUMOSTEM administration to PMA 36~40 weeks
Change in vital signs - Blood pressure	Change in systolic and diastolic blood pressure from baseline(PNEUMOSTEM administration day) measured in mmHg.	From PNEUMOSTEM administration to PMA 36~40 weeks
Change in vital signs - Body temperature	Change in body temperature from baseline(PNEUMOSTEM administration day) measured in degrees celsius.	From PNEUMOSTEM administration to PMA 36~40 weeks
Change in vital signs - Heart rate	Change in heart rate(pulse) from baseline(PNEUMOSTEM administration day) measured in beats per minute.	From PNEUMOSTEM administration to PMA 36~40 weeks
Change in vital signs - Respiratory rate	Change in respiratory rate from baseline(PNEUMOSTEM administration day) measured in breaths per minute.	From PNEUMOSTEM administration to PMA 36~40 weeks
Change in vital signs - Oxygen saturation	Change in oxygen saturation(SpO2) from baseline(PNEUMOSTEM administration day) measure as percentage.	From PNEUMOSTEM administration to PMA 36~40 weeks
Abnormal laboratory values - Hematology	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).	Once at screening
Abnormal laboratory values - Blood chemistry	Incidence of clinically significant abnormal blood chemistry values including C-reactive protein(CRP) and other relevant biochemical markers.	At screening and within 24 hours after PNEUMOSTEM administration
Abnormal Electrocardiography findings	Incidence of clinically significant abnormal findings on continuous electrocardiography monitoring including arrhythmias, conduction abnormalities, or other cardiac electrical disturbances.	From PNEUMOSTEM administration to PMA 36~40 weeks
Incidence of infectious disease	Incidence of infectious disease identified by blood and tracheal aspirate(TTA) cultures with component analysis and pathogen identification.	At screening and weekly from baseline(PNEUMOSTEM adminitration day) to week 2
Abnormal blood gas analysis	Incidence of clinically significant abnormal blood gas analysis results for assessment of respiratory and metabolic status including PH, PaO2, PaCO2 and base excess.	From PNEUMOSTEM administration to postnatal day 28
Abnormal findings on chest x-ray	Incidence of clinically significant abnormal findings on chest radiography including evaluation for pleural effusion, pneumothorax, infiltrates, or other pulmonary abnormalities.	At screening, within 24 hours after PNEUMOSTEM adminitration, a week after PNEUMOSTEM administration, postnatal day 28 and at between PMA 36~40 weeks

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Premature Birth
• Other Study ID Numbers: 2025-10-080

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No