Mesenchymal Stromal Cell Therapy to Prevent Bronchopulmonary Dysplasia in Extreme Preterm Infants

Official title

Mesenchymal Stromal Cells in Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia - A Phase 2 Multi-Centre Double Blind Randomized Controlled Trial

Overview

This clinical trial aims to evaluate the safety and efficacy of mesenchymal stromal cell (MSC) therapy in extreme preterm infants to prevent bronchopulmonary dysplasia, the main respiratory complication of preterm birth. Study participants will receive either multiple intravenous doses (total of 3 doses) of MSC derived from human donor umbilical cord tissue (intervention group) or no uc-MSC injection (control group) to confirm the safety of IV MSC in extreme preterm infants and evaluate the potential benefit of MSC therapy on their respiratory health as well as on other complications related to preterm birth.

Detailed description

Include Background...

Interventions

• Biological Human Allogenic Umbilical Cord Mesenchymal Stromal Cells
  IV administration of uc-MSC every 7 days ± 1 day for 3 weeks. Randomized double blinded
• Other Sham procedure control
  Sham procedure (mimic IV catheter insertion adn cell product infusion behing a screen). Repeated weekly for 3 weeks

Primary outcome measures

• Number of mechanical ventilation-free days accounting for mortality [Time frame: 120 days]

Secondary outcome measures (11)

• Effects of uc-MSCs on the date of extubation for participants. [Time frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months]
• Effects of uc-MSCs on the rate of survival without moderate or severe BPD at 36 weeks corrected age. [Time frame: BPD severity will be assessed for each participant at 36 weeks of corrected age]
• Effects of uc-MSCs on the Number of Participants receiving open-label dexamethasone for severe chronic lung disease [Time frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months]
• Effects of uc-MSCs on the duration of respiratory support. [Time frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months]
• Effects of uc-MSCs on the levels of respiratory support at 36 weeks CA, 40 weeks CA and at hospital discharge. [Time frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months]
• Effects of uc-MSCs on the occurrence of pulmonary hypertension related to severe BPD [Time frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months]
• Neurodevelopment and health outcomes at 24 months corrected age (Bayleys) [Time frame: Assessment will be scheduled at 24 months corrected age.]
• Evaluation of safety of IV administration of UC-MSCs: Dose Limiting toxicity [Time frame: 24-hours post uc-MSC injection]
• Evaluation of safety of IV administration of UC-MSCs: potential adverse event [Time frame: within 1 week post uc-MSC injection]
• Long-term participant safety follow-up [Time frame: From enrollment until participant is 10 years of age.]
• Complications of prematurity (assessed at time of hospital discharge) [Time frame: From date of randomization until the date of discharge home or date of death from any cause, whichever came first, assessed up to 12 months]

Eligibility criteria

Inclusion criteria

• Gestational age (GA) less than 28+0 weeks
• Post-natal age between 4 and 14 days of life
• Invasive ventilation with oxygen requirement:

• On mechanical ventilation: intubated patient with any of the following ventilation modes: conventional, HFO or Jet ventilation:
• With requirement of FiO2: FiO2 >= 30% and for at least 12 hours over 24 hours (i.e. flowsheets, FiO2 histogram)

Exclusion criteria

• Congenital anomaly:

• Genetic and chromosomal syndromes (e.g., Trisomy 13, Trisomy 18, Trisomy 21): either patient with high suspicion (antenatal findings, clinical features) or documented syndrome by genetic testing.
• Major congenital anomalies including cardiac (i.e., congenital heart defects, NB. PDA is not considered an exclusion criterion), neurological (e.g., holoprosencephaly, anencephaly), gastrointestinal (e.g., gastroschisis, omphalocele), pulmonary (e.g., congenital diaphragmatic hernia) anomalies.
• Inborn errors of metabolism.
• Hemodynamic instability (shock):

• Hemodynamic instability with impaired end-organ perfusion (metabolic acidosis with increased lactate and/or decreased urine output).
• Requirements for fluid bolus, inotrope or vasopressor medication
• Severe sepsis:

• Signs of hemodynamic instability and requiring at least one fluid bolus.
• And a positive blood or cerebrospinal fluid culture.
• Pneumothorax: Pneumothorax with a chest tube in place
• Severe pulmonary hemorrhage:

• Active pulmonary hemorrhage (i.e., frank blood coming from the endotracheal tube.
• And at least one of the following criteria: a)hemodynamic instability. b) blood product transfusion (packed red blood cells, platelets, fresh frozen plasma)
• Extubation: If Extubation planned within the next 24 hours (post first uc-MSC administration/sham procedure).
• Patient is not expected to survive:

• Redirection of care.
• Patient is moribund

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Canada · 8 centers

• Royal Alexandra Hospital/Stollery Children's Hospital — Edmonton
• McMaster Children's Hospital — Hamilton
• The Ottawa Hospital — Ottawa
• Sunnybrook Health Sciences Ctr — Toronto
• Mount Sinai Hospital — Toronto
• CHU Sainte-Justine — Montreal
• McGill Montreal Children's Hospital — Montreal
• Université Laval — Québec

Publications

• Renesme L, Ferretti E, Horth C, Grimwood R, Da Sylva L, Olson V, Cyr-Depauw C, Freund D, Rudiger M, Mobius MA, Hodgins S, Khan S, Courtman D, Fergusson DA, Thebaud B. Helping Underdeveloped Lungs with Cells (HULC-2): mesenchymal stromal cells in extreme preterm infants at risk of developing bronchopulmonary dysplasia - a study protocol of a phase 2 multicentre double blind randomised controlled tr PMID 42409407

Identifiers

NCT: NCT07058025 · HULC-2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗