Bronchopulmonary Dysplasia (BPD), ELGAN (22-28SA)
Conditions
Keywords
Phase II clinical trial, Mesenchymal stromal cell, Cell therapy, Preterm infant, Bronchopulmonary Dysplasia, Extremely low gestational age neonates
Brief summary
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
BIOLOGICALHuman Allogenic Umbilical Cord Mesenchymal Stromal Cells
IV administration of uc-MSC every 7 days ± 1 day for 3 weeks. Randomized double blinded
Sham procedure (mimic IV catheter insertion adn cell product infusion behing a screen). Repeated weekly for 3 weeks
Sponsors
Canadian Institutes of Health Research (CIHR)
Stem Cell Network
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Parents of the participants.
Intervention model description
Intervention group: Participants allocated in the intervention group will receive multidose of UC-MSCs as follow: * Dose: each dose consists of 10x106 cells/kilograms of bodyweight. * Administration protocol: weekly 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 using a syringe pump over 15 minutes. Control group: 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)
Eligibility
Sex/Gender
ALL
Age
4 Days to 14 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of mechanical ventilation-free days accounting for mortality | 120 days | The study primary outcome is the number of mechanical ventilation-free days accounting for mortality. Mechanical ventilation is defined by artificial ventilation using an endotracheal tube. For study purpose, this outcome will be measured at 120 days after randomization. To account for mortality, any death within 120 days post randomization will be counted as 0 mechanical ventilation-free day (worse outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long-term participant safety follow-up | From enrollment until participant is 10 years of age. | We plan to have annual parental interviews via telephone until the participant is 10 years old. This is to assess the respiratory status and any new diagnoses of study participants. |
| Effects of uc-MSCs on the date of extubation for participants. | 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 | This respiratory outcome will be measured to determine if uc-MSCs have an effect on the date of extubation for participants |
| Effects of uc-MSCs on the rate of survival without moderate or severe BPD at 36 weeks corrected age. | BPD severity will be assessed for each participant at 36 weeks of corrected age | This will assess if uc-MSCs impact survival with moderate or severe Bronchopulmonary dysplasia. |
| Effects of uc-MSCs on the Number of Participants receiving open-label dexamethasone for severe chronic lung disease | 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 | This will help us determine if the intervention reduces use of dexamethasone for the treatment of severe chronic lung disease. |
| Effects of uc-MSCs on the duration of respiratory support. | 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 | Since ventilation damages underdeveloped lungs, determining the duration of ventilation is important to monitor as an outcome of uc-MSCs. We will collect the total number of days on mechanical ventilation, non-invasive ventilation, and oxygen therapy during the NICU hospitalization for each participant |
| Effects of uc-MSCs on the levels of respiratory support at 36 weeks CA, 40 weeks CA and at hospital discharge. | 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 | The different levels of intensity of ventilation will help us determine if uc-MSCs reduce ventilation days. The respiratory support being used are the following (Room air being the least intensive and best for participant health outcome.): mechanical ventilation vs. Continuous Positive Airway pressure/High Flow Nasal Canula, vs. Low Flow Nasal Canula vs. room air |
| Effects of uc-MSCs on the occurrence of pulmonary hypertension related to severe BPD | 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 | This will help us determine the therapeutic properties of UC-MSCs in reducing the occurrence of pulmonary hypertension related to severe BPD. Participants will be screened by echocardiography for pulmonary hypertension at 36 weeks of corrected age. Medication for chronic pulmonary hypertension will be collected. |
| Neurodevelopment and health outcomes at 24 months corrected age (Bayleys) | Assessment will be scheduled at 24 months corrected age. | The neurodevelopmental assessment will be scheduled at 24 months CA with a window of +/- 6 months (i.e., between 18 to 30 months CA). Participants will be evaluated in the Neonatal Follow-Up clinic for high-risk infants. An assessment of general health and growth will be performed, and the most recent audiology and ophthalmology results will be recorded. The Bayley Scales of Infant Develpment-4th edition will be performed by a qualified professional to further evaluate the neurodevelopment of the participant. |
| Evaluation of safety of IV administration of UC-MSCs: Dose Limiting toxicity | 24-hours post uc-MSC injection | Dose-limiting toxicity, defined as one of the following events, occurring within 24-hour post UC-MSC injection: * Death * Anaphylaxis * Increase need for respiratory support define by increase FiO2 \>30% from baseline and/or increase in mean airway pressure \> 5 cmH2O from baseline * Medications to support hemodynamic status (including management of cardiac arrest) including fluid boluses, inotropes, or vasopressors * Any SAE not expected in this patient population for which there is no alternative explanation but the IV administration of UC-MSCs and occurring within 1 week after UC-MSCs injection. |
| Evaluation of safety of IV administration of UC-MSCs: potential adverse event | within 1 week post uc-MSC injection | Any Serious Adverse Event (SAE) not expected in this patient population for which there is no alternative explanation but the IV administration of UC-MSCs and occurring within 1 week after UC-MSCs injection. |
| Complications of prematurity (assessed at time of hospital discharge) | 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 | The complications of prematurity assessed are the following: * BPD. * Patent Ductus Arteriosus requiring medical, surgical or device closure. * Intra-ventricular hemorrhage ≥ grade 3 according to Papille's classification. * Periventricular leukomalacia. * Necrotizing enterocolitis ≥ stage 2 according to Bell's classification. * Retinopathy of prematurity requiring treatment * Late-onset sepsis |
Countries
Canada
Contacts
Primary ContactBernard Thébaud, MD, PhD
Backup ContactChantal Horth
Outcome results
None listed