Mesenchymal Stromal Cells in Extreme Preterm Infants at Risk of Developing Bronchopulmonary Dysplasia - A Phase 2 Multi-Centre Double Blind Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 168
- 试验地点
- 8
- 主要终点
- Number of mechanical ventilation-free days accounting for mortality
研究概览
简要总结
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.
详细描述
Include Background...
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Parents of the participants.
入排标准
- 年龄范围
- 4 Days 至 14 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Intervention group will receive multiple IV doses of UC-MSCs
- 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.
干预措施: Human Allogenic Umbilical Cord Mesenchymal Stromal Cells (Biological)
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)
干预措施: Sham procedure control (Other)
结局指标
主要结局
Number of mechanical ventilation-free days accounting for mortality
时间窗: 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).
次要结局
- Neurodevelopment and health outcomes at 24 months corrected age (Bayleys)(Assessment will be scheduled at 24 months corrected age.)
- Evaluation of safety of IV administration of UC-MSCs: Dose Limiting toxicity(24-hours post uc-MSC injection)
- Evaluation of safety of IV administration of UC-MSCs: potential adverse event(within 1 week post uc-MSC injection)
- Long-term participant safety follow-up(From enrollment until participant is 10 years of age.)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)