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

Study Overview
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Brief Summary
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This is a non-randomized, case-controlled trial that evaluates the efficacy of autologous cord blood mononuclear cells(ACBMNC) infusion as a Treatment for BPD. The results of this trial will provide valuable clinical evidence for recommendations on the treatment of BPD in extremely preterm infants. Informed consent before birth is signed. In this prospective clinical trial, preterm neonates less than 28 weeks who previously stored ACBMNC and then suffer BPD will be assigned to be ACBMNC infusion group, while those who do not previously stored ACBMNC or then refuse ACBMNC infusion and suffer BPD will be assigned to be control group. In the ACBMNC infusion group, when BPD occurred, the pre-stored ACBMNC will be removed and rewarmed, and then ACBMNC(5×107 cells /kg) will be intravenously injected within 24 hours. The control group receives standardized treatment without special treatment. The total number of participants is 76 and the same in both groups. The primary outcome is the rate of mortality or ratio of severe BPD at 36 weeks of postmenstrual age or discharge home. The secondary outcomes will include other common preterm complication rate and the number of hospitalizations due to pneumonia within 1 year of postmenstrual age.

Detailed Description
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Study design and settings: This is a non-randomized, case-controlled trial that evaluates the efficacy of autologous cord blood mononuclear cells(ACBMNC) infusion as a Treatment for BPD. Informed consent before birth is signed. Preterm infants in the ACBMNC infusion group will have their umbilical cord blood collected after birth. Umbilical cord blood was collected into a collection bag after delivery and labeled. The collection bag was placed in a 4° refrigerator for refrigeration and sent to the Guangdong Province umbilical cord blood Bank. ACBMNC will be separated and preserved with liquid nitrogen. The total content of umbilical cord blood cells, the number of mononuclear cells per ml and the volume before and after separation were provided immediately for the later calculation of the total volume of infusion. In this prospective clinical trial, preterm neonates less than 28 weeks who previously stored ACBMNC and then suffer BPD will be assigned to be ACBMNC infusion group, while those who do not previously stored ACBMNC or then refuse ACBMNC infusion and suffer BPD will be assigned to be control group. In the ACBMNC infusion group, when BPD occurred, the pre-stored ACBMNC will be removed and rewarmed, and then ACBMNC(5×107 cells /kg) will be intravenously injected within 24 hours. The control group receives standardized treatment without special treatment. The total number of participants is 76 and the same in both groups. The primary outcome is the rate of mortality or ratio of severe BPD at 36 weeks of postmenstrual age or discharge home. The secondary outcomes will include other common preterm complication rate and the number of hospitalizations due to pneumonia within 1 year of postmenstrual age. Trial treatment methods: Informed consent before birth will be signed by the parents. All premature infants included in the study received standardized treatment after admission to the NICU. In the ACBMNC infusion group, when BPD occurred, the pre-stored ACBMNC will be removed and rewarmed, and then ACBMNC(5×107 cells /kg) will be intravenously injected within 24 hours. The control group receives standardized treatment without special treatment.

Official Title
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Effect of Autologous Cord Blood Mononuclear Cells for Treatment of Bronchopulmonary Dysplasia in Extremely Preterm Neonates: a Non-Randomized Case-Control Trial Study

Conditions
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BPD

Intervention / Treatment
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* Biological: autologous cord blood mononuclear cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.born at study hospital; 2. singleton birth; 3. less than 28 weeks GA 4.Signed informed consent obtained; 5. Umbilical cord blood collection and testing qualified; 6.Diagnosed with BPD Exclusion Criteria: 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.

Ages Eligible for Study
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Maximum Age: 28 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a non-randomized, case-controlled trial that evaluates the efficacy of autologous cord blood mononuclear cells(ACBMNC) infusion as a Treatment for BPD.In this prospective clinical trial, preterm neonates less than 28 weeks who previously stored ACBMNC and then suffer BPD will be assigned to be ACBMNC infusion group, while those who do not previously stored ACBMNC or then refuse ACBMNC infusion and suffer BPD will be assigned to be control group. In the ACBMNC infusion group, when BPD occurred, the pre-stored ACBMNC will be removed and rewarmed, and then ACBMNC(5×107 cells /kg) will be intravenously injected within 24 hours. The control group receives standardized treatment without special treatment. The total number of participants is 76 and the same in both groups.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACBMNC infusion group<br>Those assigned to the ACBMNC group will receive intravenous autologous cord blood mononuclear cells infusion. Cell dose for all patients was targeted at 5×107 cells per kilogram. | Biological: autologous cord blood mononuclear cells<br>* preterm neonates less than 28 weeks who suffer BPD and also stored cord blood are assigned to receive intravenous autologous cord blood mononuclear cells infusion (5×107cells/kg).<br>|
| No Intervention: control group<br>The control group received standardized treatment without special treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of mortality or ratio of severe BPD | Rate of mortality or ratio of severe BPD at discharge or corrected gestational age at 36 weeks | 36 weeks of postmenstrual age or discharge home whichever comes first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of other preterm complications | Incidence of other preterm complications including intraventricular hemorrhage (IVH), periventricular leukomalacia(PVL), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), ventilation-associated pneumonia (VAP) and late onset sepsis (LOS) | 36 weeks of postmenstrual age or the discharge home whichever comes first. | 
| The number of hospitalizations | To compare the number of hospitalizations due to pneumonia, wheezing, asthma, nighttime cough, need for oxygen therapy, height, weight, nervous system development within 1 or 2 year of postmenstrual age. Long-term outcome. | 1 or 2 year of postmenstrual age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous cord blood mononuclear cells, bronchopulmonary dysplasia, extremely preterm neonates