Cerebral Infarction, Hypoxic Ischemic Encephalopathy
Conditions
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.
Interventions
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.
DEVICEHypothermia
Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
Sponsors
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Children's Hospital of Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Hours
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | From birth to the age of 18 months | The relative frequency of deaths in each group. |
| Disability Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain Parenchyma Alterations(MRI) | At the age of 7 Days | Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7. |
| Neurodevelopment(Bayley Scores) | 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). |
| Brain Structural Alterations(MRI) | 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) | At the age of 7 days | Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7. |
| Number of Adverse Events | 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) | 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) | 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) | 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 | 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 | 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 | 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 | 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. |
Countries
China
Outcome results
None listed