Mesenchymal Stromal Cell Therapy to Prevent Bronchopulmonary Dysplasia in Extreme Preterm Infants (HULC-2)

Ottawa Hospital Research Institute

Status and phase: Not yet enrolling; Phase 2

Conditions: Bronchopulmonary Dysplasia (BPD); ELGAN (22-28SA)

Treatments: Other: Sham procedure control; Biological: Human Allogenic Umbilical Cord Mesenchymal Stromal Cells

Study type: Interventional

Funder types: Other

Identifiers

NCT07058025

HULC-2

Details and patient eligibility

About

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.

Full description

Include Background...

Enrollment: 168 estimated patients

Sex: All

Ages: 4 to 14 days old

Volunteers: No Healthy Volunteers

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

1. 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.

2. 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

3. Severe sepsis:

   • Signs of hemodynamic instability and requiring at least one fluid bolus.
   • And a positive blood or cerebrospinal fluid culture.

4. Pneumothorax: Pneumothorax with a chest tube in place

5. 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)

6. Extubation: If Extubation planned within the next 24 hours (post first uc-MSC administration/sham procedure).

7. Patient is not expected to survive:

   • Redirection of care.
   • Patient is moribund

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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168 participants in 2 patient groups

Intervention group will receive multiple IV doses of UC-MSCs

Experimental group

Description:

* Dose: each dose consists of 10 million cells/kilograms of bodyweight. * Administration protocol: weekly (7 days ± 1 day) IV dose of UC-MSCs for 3 weeks (Total of 3 doses) * Route of administration: IV infusion on peripheral intravenous catheter. The UC-MSC solution will be infused using a syringe pump over 15 minutes, and after the UCMSC infusion, an additional volume of normal saline will be infused over 15 minutes.

Treatment:

Biological: Human Allogenic Umbilical Cord Mesenchymal Stromal Cells

Control group

Sham Comparator group

Description:

Participants allocated in the control group will receive a sham procedure weekly for 3 weeks. A syringe of normal saline brought to bedside, but it will not be administered. The physician and bedside nurse will perform the sham procedure behind a screen (they will mimic IV catheter insertion and cell product injection)

Treatment:

Other: Sham procedure control