Clinical trial NCT04440670: Effect of Autologous Cord Blood Mononuclear Cells for Prevention of Bronchopulmonary Dysplasia or Death in Extremely Preterm Neonates
Official title: Effect of Autologous Cord Blood Mononuclear Cells for Prevention of Bronchopulmonary Dysplasia or Death in Extremely Preterm Neonates: a Placebo-controlled Randomized Multicenter Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: BPD
Keywords: Autologous cord blood mononuclear cells
bronchopulmonary dysplasia
extremely preterm neonates
Lead sponsor: Guangdong Women and Children Hospital
Sponsor class: OTHER
Collaborators: name: Foshan Fuxing Chancheng Central Hospital
name: Foshan Women's and Children's Hospital
name: Hexian Memorial Affiliated Hospital of Southern Medical University
name: Heyuan Women and Children Hospital
name: Dongguan Women and Children Hospital
name: Guangzhou Huadu Women and Children Hospital
name: Shunde Women and Children Hospital
name: Guangdong Cord Blood Bank
name: Huangdu Distric Women and Children Hospital
name: Longgang Distric Women and Children Hospital,Shenzhen
name: Zhongshan Boai Hospital
name: Huizhou first Women and Children Hospital
name: Huizhou second Women and Children Hospital
First posted: 2020-06-22
Enrollment: 140
Sex: ALL
Minimum age (years): 0
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In this prospective, randomized controlled double-blind multi-center clinical trial, 140 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.
Primary purpose: PREVENTION

Brief summary: 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 or death. 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, 140 extremely preterm neonates less than 28 weeks are randomly assigned to receive intravenous autologous cord blood mononuclear cells infusion (targeted dose of 5×107cells/kg but no less than 1×107cells/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, BPD severity, 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: frequency of bronchopulmonary dysplasia or death
timeFrame: 36 weeks of postmenstrual age or discharge home whichever comes first.
Secondary outcomes:
measure: mortality
timeFrame: 36 weeks of postmenstrual age or the discharge
Other outcomes:
Locations:
city: Dongguan
country: China
facility: Ren Xuejun
state: Guangdong
city: Guangzhou
country: China
facility: Jie Yang
state: Guangdong
Study officials:
affiliation: Guangdong Women and Children Hospital
name: Jie Yang
role: STUDY_CHAIR
References: