Study design and settings:
This present study will be a randomized, placebo-controlled, double-blinded, multi-center
trial to be conducted at 12 medical centers in tertiary hospitals with Neonatal Intensive
Care Unit that were selected by the expert committee. A total of 140 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.
Sample size:
Based on our previous study and others' study, we found the ACBMNC infusion was effective in
reducing respiratory support duration in preterm infants. The rate of BPD among extremely
preterm infants in our NICU was 60% (pA). What we expect to be an intended (or at least
acceptable) effect of the ACBMNC infusion is 25 % reduction in frequency of BPD(pB:35%). To
detect this difference with a sensitivity of 80% and an error probability of 5%, at least 59
patients per randomization group will be required using the following formula:
n=(pA(1-pA)/κ+pB(1-pB))((z1-α/2+z1-β)/(pA-pB))2 To account for the possibility of as high as
20% loss to follow-up, our estimated sample size is 140 cases totally.
Objectives:
Primary objective： The primary objective of this trial is to evaluate the efficacy of ACBMNC
infusion in preventing bronchopulmonary dysplasia or death 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 BPD severity
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.