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

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

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.

Study Overview

• Status: Recruiting
• Conditions: BPD
• Intervention / Treatment: Biological: autologous cord blood mononuclear cells; Biological: normal saline

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.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: zhuxiao Ren, MD; Phone Number: +8613538984634; Email: renzhx1990@163.com

Study Locations

• China
  • Guangdong
    • Dongguan, Guangdong, China
      • Recruiting
      • Ren Xuejun
      • Contact: Ren Xuejun, MD
    • Guangzhou, Guangdong, China, 511442
      • Recruiting
      • Jie Yang
      • Contact: Jie Yang, PHD; Phone Number: 020 39151777; Email: jieyang@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 6 months (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACBMNC infusion group; 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.	Biological: autologous cord blood mononuclear cells; 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
Placebo Comparator: control group; Those in control group will receive an infusion of a placebo solution which is normal saline with the same volume.	Biological: normal saline; preterm neonates less than 28 weeks are assigned to receive normal saline within 24 hours after birth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequency of bronchopulmonary dysplasia or death	The frequency of bronchopulmonary dysplasia or death at 36 weeks of postmenstrual age or discharge home whichever comes first.	36 weeks of postmenstrual age or discharge home whichever comes first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality	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.	36 weeks of postmenstrual age or the discharge

Collaborators and Investigators

• Sponsor: Guangdong Women and Children Hospital
• Collaborators: Hexian Memorial Affiliated Hospital of Southern Medical University; Foshan Women and Children Hospital; Heyuan Women and Children Hospital; Dongguan Women and Children Hospital; Guangzhou Huadu Women and Children Hospital; Guangdong Cord Blood Bank; Foshan Fuxing Chancheng Central Hospital; Shunde Women and Children Hospital; Huangdu Distric Women and Children Hospital; Longgang Distric Women and Children Hospital,Shenzhen; Zhongshan Boai Hospital; Huizhou first Women and Children Hospital; Huizhou second Women and Children Hospital
• Investigators: Study Chair: Jie Yang, Guangdong Women and Children Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 22, 2020

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: bronchopulmonary dysplasia; Autologous cord blood mononuclear cells; extremely preterm neonates
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia
• Other Study ID Numbers: Guang dong W C H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: public
• IPD Sharing Time Frame: all time
• IPD Sharing Access Criteria: all
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No