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Neuroprotective Effect of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonatal Encephalopathy

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ClinicalTrials.gov Identifier: NCT02551003
Recruitment Status : Recruiting
First Posted : September 16, 2015
Last Update Posted : February 20, 2020
Sponsor:
Collaborators:
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Information provided by (Responsible Party):
Children's Hospital of Fudan University

Tracking Information
First Submitted Date  ICMJE September 4, 2015
First Posted Date  ICMJE September 16, 2015
Last Update Posted Date February 20, 2020
Actual Study Start Date  ICMJE September 8, 2015
Estimated Primary Completion Date December 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2015)
  • Mortality [ Time Frame: From birth to the age of 18 months ]
    The relative frequency of deaths in each group.
  • Disability Rate [ Time Frame: From birth to the age of 18 months ]
    Disability, defined as a physical or mental handicap, especially one that prevents a person from living a full, normal life or from holding a gainful job.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2015)
  • Neurodevelopment(Bayley Scores) [ Time Frame: At the age of 12 months ]
    Efficacy of levetiracetam by assessment of the change from baseline to 12 months in neurodevelopment via Bayley Scores of Infant Development Mental Development Index (BSID).
  • Neurodevelopment(Bayley Scores) [ Time Frame: At the age of 18 months ]
    Efficacy of levetiracetam by assessment of the change from baseline to 18 months in neurodevelopment via Bayley Scores of Infant Development Mental Development Index (BSID).
  • Brain Structural Alterations(MRI) [ Time Frame: At the age of 7 days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.
  • Brain Structural Alterations(MRI) [ Time Frame: At the age of 28 days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.
  • Brain Structural Alterations(MRI) [ Time Frame: At the age of 12 months ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months old.
  • Brain Parenchyma Alterations(MRI) [ Time Frame: At the age of 7 Days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.
  • Brain Parenchyma Alterations(MRI) [ Time Frame: At the age of 28 days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.
  • Brain Parenchyma Alterations(MRI) [ Time Frame: At the age of 12 months ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months old.
  • Intracranial Hemorrhage(MRI) [ Time Frame: At the age of 7 days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.
  • Intracranial Hemorrhage(MRI) [ Time Frame: At the age of Day 28 ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.
  • Intracranial Hemorrhage(MRI) [ Time Frame: At the age of 12 months ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months.
  • Number of Adverse Events [ Time Frame: In 72 hours ]
    This is a composition of general appearance includes abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
  • Number of Adverse Events(Blood Pressure) [ Time Frame: In 72 hours ]
    This is a composition of general appearance, blood pressure, pulse, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
  • Number of Adverse Events(Pulse) [ Time Frame: In 72 hours ]
    This is a composition of general appearance, blood pressure, pulse, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
  • Number of Adverse Events(Respiratory) [ Time Frame: In 72 hours ]
    This is a composition of general appearance, blood pressure, pulse, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
  • Incidence of Complication [ Time Frame: From birth to the age of 28 days in each treatment period ]
    To gain the incidence of Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, intraventricular hemorrhage(IVH), periventricular leukomalacia(PVL), seizure, necrotizing enterocolitis (NEC), persistent ductus arterious (PDA), apnea of prematurity, pulmonary haemorrhage, pulmonary hypertension, Prolonged blood coagulation time, retinopathy of prematurity(ROP), cardiac arrhythmia, major venous thrombosis, Renal failure treated with dialysis, pneumonia, pulmonary airleak and chronic lung disease.
  • SDF-1 in Serum [ Time Frame: At the age of 4 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.
  • SDF-1 in Serum [ Time Frame: At the age of 14 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.
  • TNF-alpha in Serum [ Time Frame: At the age of 4 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.
  • TNF-alpha in Serum [ Time Frame: At the age of 14 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.
  • IL-1 in Serum [ Time Frame: At the age of 4 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.
  • IL-1 in Serum [ Time Frame: At the age of 14 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neuroprotective Effect of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonatal Encephalopathy
Official Title  ICMJE A Multi-Centre Safety and Efficacy Study of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonates Encephalopathy in China
Brief Summary This study examines the effect of cord blood in the treatment of newborn infants with neonatal encephalopathy in combination with hypothermia, which is the standard treatment for this condition. The hypothesis is that the cord blood + hypothermia combination will produce better neuroprotection than the standard treatment of hypothermia alone.
Detailed Description The primary aim of this study is to determine the neuroprotective effect of intravenous administration of autologous cord blood in neonates with severe encephalopathy (hypoxic ischemic encephalopathy or cerebral infarction). It is hypothesized that the administration of autologous cord blood will be safe and well tolerated in neonates with severe encephalopathy. If a neonate is born with signs of moderate to severe encephalopathy and cooled for the encephalopathy, the neonate will receive their own cord blood. The cord blood cells are divided into 3 doses and infused at 24, 48, and 72 hours after the birth. Infants will be randomised to treatment with autologous cord blood and hypothermia or hypothermia only and followed for safety and neurodevelopmental outcome up to 18 months. All infants in both groups will be treated with hypothermia for 72 hours started within 6 hours of delivery and infants who allocated to hypothermia and xenon will also receive autologous cord blood in 24 hours from birth through a purpose designed delivery system. Additionally, postnatal neuro-developmental outcomes in neonates with encephalopathy after autologous cord blood therapy will be measured; HIE injury to the neonate/infant brain post autologous cord blood therapy by imaging will be characterized; MRI's will be obtained per clinical routine; serum levels of selected cytokine and neurotrophic factors in neonates with HIE before and after autologous cord blood therapy will be compared and immune cell phenotype and function in neonates with HIE before and after autologous cord blood therapy will be compared.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypoxic Ischemic Encephalopathy
  • Cerebral Infarction
Intervention  ICMJE
  • Drug: Autologous cord blood
    Autologous cord blood will be collected after birth and administered in divided aliquots during the first 3 days of life. At the same time, babies will referred to neonatal intensive care unit for hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
  • Device: Hypothermia
    Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
Study Arms  ICMJE
  • Experimental: Cord blood with hypothermia
    Autologous cord blood will be collected after birth and stored in Cord Blood Bank of hospital. All cord blood samples are routinely performed by dedicated, trained UCB collection staff and is restricted to deliveries of mothers who have given prior written informed consent for collection. If the mother delivered a baby with signs of HIE or cerebral infarction, Bank staff collected UCB utilizing standard procedures. Collected UCB was transported at roomtemperature in validated shippers to the NICU. Infusions were started when cells and study staff were available for administration and monitoring. Infants received up to 3 infusions, with the first dose as soon as possible after birth, and at, 48, and 72 postnatal hours. At the same time, babies will referred to neonatal intensive care unit for hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
    Intervention: Drug: Autologous cord blood
  • Active Comparator: Hypothermia
    Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
    Intervention: Device: Hypothermia
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 14, 2015)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2020
Estimated Primary Completion Date December 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Gestational age ≥ 34 weeks
  2. Birth weight ≥ 1800 grams
  3. 10-minute Apgar score ≤5 or continued need for ventilation or severe acidosis, defined as pH <7.0
  4. Moderate to severe encephalopathy (Sarnat II to III)
  5. A moderately or severely abnormal background aEEG voltage, or seizures identified by aEEG, if monitored
  6. Up to 24 hours of age
  7. Autologous umbilical cord blood available to infuse 3 doses within 72 hours after birth
  8. Parental informed consent

Exclusion Criteria:

  1. Known major congenital anomalies, such as chromosomal anomalies, heart diseases
  2. Major intracranial hemorrhage identified by brain ultrasonography or computed tomography
  3. Severe intrauterine growth restriction (weight <1800g)
  4. Severe infectious disease, such as sepsis
  5. Inability to enroll by 24 hours of age
  6. Volume of collected cord blood <40 ml
  7. Infants in extremis for whom no additional intensive therapy will be offered by attending neonatologist
  8. Parents refuse consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 24 Hours   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wenhao Zhou, Doctor zwhchfu@126.com
Contact: Guoqiang Cheng, Doctor gqchengcm@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02551003
Other Study ID Numbers  ICMJE CHFudanU_NNICU1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Hospital of Fudan University
Study Sponsor  ICMJE Children's Hospital of Fudan University
Collaborators  ICMJE
  • Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
  • Guangzhou Women and Children's Medical Center
Investigators  ICMJE
Study Chair: Wenhao Zhou, Doctor Children's Hospital of Fudan University
PRS Account Children's Hospital of Fudan University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP