Other HIE/NE SUMMARY – Updated April, 2014
STUDY DESIGN/
PHASE/NAME
Phase 1 Pilot
N=5
INTERVENTION/
CONTROL
Olympic Cool Cap
PRIMARY OUTCOME
SECONDARY OUTCOMES
<1200 g
Trauma, IVH
Feasibility
2x weekly injections
cerebrolysin 10 injections
Control: standard care
FT neonate>36 weeks, aged
1-6 mths
Congenital abnormalities
Severe IUGR
meningitis
Neurodevelopmental
follow up after 1 course
(age 3 mths)
Neurodevelopmental
follow up after 12 mths
(aged 18mths)
Up to 4 doses of cord blood
cells
Control: historical
Acute perinatal event
Signs of enceph by 6 hrs
>34 wks
Inability to enrol by 14 days
Congenital abnormalities
<1800g
Adverse events during
transfusions (first 18 days)
Neurodevelopmental
outcome (4-6mths; 9-12
mths)
6 doses of 2-iminobiotin in
20 hours
Control: placebo
>= 36 and <44 weeks
<= 6 hours after birth
Mod-severe enceph
Standard care without
hypothermia
Congenital abnormalities
Severe growth restriction
Lac/NAA in basal ganglia
measured with MRS (age 37 days)
EEG seizures
>= 36 weeks
Seizure burden
Control: Clinical seizures
<=72 hours after birth
Congenital anomalies of
CNS
Moribund infants – no
further aggressive
treatment
Metabolic disorders or
documented CNS infections
Neuro-muscular blockade
Congenital brain
malformation
Inbuilt error metabolism
Genetic syndrome
Major congenital
malformation
TORCH infection
Optimal dose finding –
effective seizure reduction
No control
Cerebrolysin
Phase 1
N= 25
EXCLUSION
>32 and <36 wks
<6hrs
Previous participant has 7
day CUS follow up
Cooling in preterm with HIE
Phase 1
N=40
INCLUSION
MEASURES
N/A
Autologous cord blood cells
Phase 2
N=66
2-Iminobiotin in neonates
with perinatal asphyxia
Pilot, prospective,
randomized
N=40
The Impact of
Electroencephalographic
(EEG) Seizure Treatment in
Near Term ≥ 36 Weeks
Gestation and Term Infants
With
Neonatal Encephalopathy
Phase 1 and 2
N=49
Mod-severe enceph OR
suspected/definite
neonatal seizures
Bumetanide (+standard
phenobarbital)
37-43 weeks
<48 hours old
NEMO1
1 or more criteria of
enceph or seizures
Composite endpoint
survival at 48h with normal
aEEG
Presence of combined
event: death < 2 years old
or mod-severe disability at
18-24 months
MRI (6 mths)
MRI (3-7 days old)
aEEG
Mortality
LOS in NICU level III
Neurodevelopmental
status (3,6,12,18,24
months)
Safety
Pharmacokinetics during
treatment
Neurological status
Seizures
MRI
Standardized tests incl
AIMS, BSID-III, CBCL,
general movements
Assessment of neuromotor
disability and
neurodevelopmental
evaluation
Other HIE/NE SUMMARY – Updated April, 2014
STUDY DESIGN/
PHASE/NAME
INTERVENTION/
CONTROL
Randomized single blind
N=24
Protein supplementation
until 12 months age
Protein supplementation in
infants with brain injury
Control: standard diet
Phase 1 Pilot
N=38
Bumetanide + standard
phenobarbital
Pilot study of bumetanide
for newborn seizures
Control: standard
phenobarbital + saline
placebo
Phase 4 (completed)
N=95
Single high dose vit E and 2
doses vit C
Single High Dose Vitamin C,
E in Severe Birth Asphyxia
No control
INCLUSION
NICU
Known/suspected brain
injury
>=48 hours old
<3 weeks old
Post-conceptional age 3344 weeks
Risk for seizure OR
suspected clinical seizure
Apgar score of <6 at 5
minutes
Clinical features suggestive
of neonatal
encephalopathy (coma,
seizures or hypotonia)
EXCLUSION
Diuretic treatment last 24h
Total serum bilirubin
>15mg/dl
Other anticonvulsant meds
Anuria/renal failure
Severe electrolyte
depletion
Congenital or
posthemorrhagic
hydrocephalus
Major congenital brain
malformations
Congenital gastrointestinal
malformations or Bell Stage
III NEC
Inborn errors of
metabolism
Chromosomal
abnormalities
Significant cardiac disease
Transient metabolic
abnormalities causing
seizures
Receiving ECMO therapy
because of altered
bumetanide
pharmacokinetics by ECMO
Contraindications to
bumetanide
Diuretics
Total serum bilirubin
>15mg/dL
Newborns given
>=40mg/kg phenobarbital
Loading doses of antiepileptic drugs other than
phenobarbital
Newborn hospitalized in
neonatal intensive care
unit (NICU) after 6 hours of
birth
Gestational age <32 weeks.
Lethal congenital anomaly
PRIMARY OUTCOME
SECONDARY OUTCOMES
MEASURES
Head circumference
Neurodevelopmental
outcome (18-22 months)
Weight and length (3,6,12
months)
Metabolic acidosis: blood
urea nitrogen and CO2
from renal panel (10 and
30 days post study
initiation)
Bayley Scales Infant
Development
Pharmacokinetics and
safety of bumetanide (EEG)
Feasibility of novel study
design
Reduction of adverse
neurodevelopmental
sequelae
Mortality and morbidity
Role of single dose vit E/vit
C in progression/resolution
of HIE
Other HIE/NE SUMMARY – Updated April, 2014
STUDY DESIGN/
PHASE/NAME
Prospective, observational
N=57
INTERVENTION/
CONTROL
Mild NE (no cooling)
INCLUSION
Birth weight >=1800g and
>=36 weeks
No control
Prospective research in
infants with mild
encephalopathy (PRIME)
Phase 3 (completed)
N=40,000
Neonatal resuscitation in
Zambia
Prospective observational
N=30
NICU admission for
possible hypothermia
Combined Neonatal
Resuscitation Program and
Essential Newborn Care
Program
Control: Essential Newborn
Care Program
Neonates with suspected
HIE
Magnetic Resonance
Imaging and Spectroscopy
Biomarkers of Neonatal
Hypoxic Ischemic
Encephalopathy
Prospective observational
N=600
Term HIE (umbilical cord
blood)
BiHiVE2 Study
Control: healthy term
neonates (umbilical cord
blood)
Birth weight >=1500g
Born at participating
hospitals
EXCLUSION
Normal neurological exam
Major congenital
abnormalities
No informed consent
Passive/active cooling prior
to NICU
Seizures or
moderate/severe NE with
hypothermia
Stillbirths
Lethal malformations
<36 weeks
Up to 2 weeks old
Suspected HIE
Informed consent
Up to one hour old
>36 weeks
HIE group: Clinical markers
of HIE
PRIMARY OUTCOME
Neurological dysfunction,
brain injury and/or
abnormality
Seizures
Length of hospital stay
Need for gavage
feeds/gastrostomy
Mortality
Long-term
neurodevelopment
Neonatal mortality
Neonatal mortality due to
perinatal asphyxia
Self efficacy, knowledge,
performance and
competence in neonatal
resuscitation
Apgar scores at 5 minutes
Prognostic accuracy of MRI
and MRS for motor
outcome age 2
Sensitivity of lactate editing
MR spectroscopy
(software) relative to
standard MR sequence
Outborn babies
SECONDARY OUTCOMES
EEG confirmed HIE
Neurodevelopmental
outcome at 2 years
MEASURES
MRI, aEEG, neurological
exam
Bayley III
GMFCS
BSID-III