Effect of Autologous Cord Blood Mononuclear Cells for Prevention of Bronchopulmonary Dysplasia in Extremely Preterm Neonates

Effect of Autologous Cord Blood Mononuclear Cells for Prevention of Bronchopulmonary Dysplasia in Extremely Preterm Neonates

Effect of Autologous Cord Blood Mononuclear Cells for Prevention of Bronchopulmonary Dysplasia in Extremely Preterm Neonates: a Placebo-controlled Randomized Multicenter Trial

Foshan Chancheng Central Hospital, Foshan Women and Children Hospital, Hexian Memorial Affiliated Hospital of Southern Medical University, Heyuan Women and Children Hospital, Dongguan Women and Children Hospital, Guangzhou Huadu Women and Children Hospital, The fifth Affiliated Hospital of Guangzhou Medcial University, Guangdong Cord Blood Bank, Dongguang People Hospital

This is the first and largest randomized, controlled, blinded trial that evaluates the efficacy of autologous cord blood mononuclear cells infusion as a prevention therapy for BPD. The results of this trial will provide valuable clinical evidence for recommendations on the management of BPD in extremely preterm infants. In this prospective, randomized controlled double-blind multi-center clinical trial, 200 preterm neonates less than 28 weeks are randomly assigned to receive intravenous autologous cord blood mononuclear cells infusion (5×107cells/kg) or placebo ( normal saline) within 24 hours after birth in a 1:1 ratio using a central randomization system. The primary outcome is survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age or discharge home. The secondary outcomes will include mortality rate, other common preterm complication rate, respiratory support duration, the length and cost of hospitalization and long term outcomes after two years follow up post infusion.

Study design and settings: This present study will be a randomized, placebo-controlled, double-blinded, multi-center trial to be conducted at 14 medical centers in tertiary hospitals with Neonatal Intensive Care Unit that were selected by the expert committee. A total of 200 neonates fulfilling the eligibility criteria will be enrolled. Subsequently, the participants will be randomly divided into two groups (ACBMNC infusion group and control (placebo) group ) in a ratio of 1:1. Objectives: Primary objective： The primary objective of this trial is to evaluate the efficacy of ACBMNC infusion in preventing bronchopulmonary dysplasia at 36 weeks of postmenstrual age or discharge home in extremely preterm infants. Secondary objectives： To compare the mortality rate at 36 weeks of postmenstrual age. To compare the rate of other common preterm complications included intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), respiratory distress syndrome (RDS), ventilation-associated pneumonia (VAP), hypoxic ischemic encephalopathy (HIE), late onset sepsis (LOS) and anemia.To compare the duration of mechanical ventilation and oxygen therapy in two groups To determine re-intubation rate and time return to BW To compare the duration of antibiotic usage To determine the long term outcomes after two years follow up Participants: Inclusion criteria: Infants fulfilling all the following inclusion criteria will be enrolled in this trial: 1. born at study hospital; 2. singleton birth; 3. less than 28 weeks GA 4.Signed informed consent obtained; 5. had available umbilical cord blood (UCB). Exclusion criteria: Those infants are excluded if they were 1. with severe congenital abnormalities; 2.with maternal clinical chorioamnionitis 3. the mother was positive for hepatitis B (HBsAg and/or HBeAg) or C virus (anti-HCV), syphilis, HIV (anti-HIV-1 and -2) or IgM against cytomegalovirus, rubella, toxoplasma and herpes simplex virus. Trial treatment methods: Soon after the preterm infant was deliveried, written consent was signed by the parents, and autologous cord blood infusion was applied to the baby in addition to routine pulmonary surfactant replacement, and mechanical ventilation support as indicated. Those assigned to the ACBMNC group received an infusion of ACBMNC with 24 h after birth. Those in control group received an infusion of a placebo solution which is normal saline with the same volume. Cell dose for all patients was targeted at 5×107 cells per kilogram.

In this prospective, randomized controlled double-blind multi-center clinical trial, 200 preterm neonates less than 28 weeks are randomly assigned to receive intravenous autologous cord blood mononuclear cells infusion (5×107cells/kg) or placebo ( normal saline) within 24 hours after birth in a 1:1 ratio using a central randomization system.

A hospital ethics committee reviewed the study data during the trials. None of them were involved in the study or aware of the treatment-group assignments of the infants. Only nurses and physicians staff conducted the infusion were aware of the treatment assignment, and these individuals had no contact with the staff who collected and analyzed the patients data. The parents are not aware of the assignment. This study is double-blinded.

Those assigned to the ACBMNC group will receive intravenous autologous cord blood mononuclear cells infusion within 24 h after birth. Cell dose for all patients was targeted at 5×107 cells per kilogram.

Those in control group will receive an infusion of a placebo solution which is normal saline with the same volume.

preterm neonates less than 28 weeks are assigned to receive intravenous autologous cord blood mononuclear cells infusion (5×107cells/kg) within 24 hours after birth

preterm neonates less than 28 weeks are assigned to receive normal saline within 24 hours after birth

The frequency of bronchopulmonary dysplasia at 36 weeks of postmenstrual age or discharge home whichever comes first.

The mortality rate. Incidence of other preterm complications including intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), respiratory distress syndrome (RDS), ventilation-associated pneumonia (VAP), late onset sepsis (LOS) and anemia . Duration of hospitalization. Duration of mechanical ventilation and oxygen therapy The frequency of re-intubation. The time (days) return to BW.

Inclusion Criteria: Infants fulfilling all the following inclusion criteria will be enrolled in this trial: 1. born at study hospital; 2. singleton birth; 3. less than 28 weeks GA 4.Signed informed consent obtained; 5. had available umbilical cord blood (UCB). Exclusion Criteria: Those infants are excluded if they were 1. with severe congenital abnormalities; 2.with maternal clinical chorioamnionitis 3. the mother was positive for hepatitis B (HBsAg and/or HBeAg) or C virus (anti-HCV), syphilis, HIV (anti-HIV-1 and -2) or IgM against cytomegalovirus, rubella, toxoplasma and herpes simplex virus.