Plain English Summary
Not provided at time of registration
Trial website
Contact information
Type
Scientific
Primary contact
Ms Debbie Nuytemans
ORCID ID
Contact details
Department of Neonatology
Emma Children's Hospital
Academic Medical Centre (AMC)
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
+31 (0)20 566 3477
HYPO-EXIT@AMC.nl
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
ZonMW Doelmatigheid 80-007022-98-07406
Study information
Scientific title
Neurodevelopmental outcome after neonatal hypoglycaemia: a multi-centre randomised controlled trial comparing intensive treatment versus expectant glucose monitoring in 'high risk' newborns
Acronym
HYPO-EXIT
Study hypothesis
Current clinical practice varies widely, especially for infants with 'moderate' hypoglycaemia, due to lack of methodological sound studies. This leads to both over- and under-treatment of hypoglycaemic infants.
This study-protocol is directed at the comparison of two accepted management strategies at both ends of the current treatment-spectrum of moderate hypoglycaemia in 'high risk' newborns: an intensive treatment versus an expectant monitoring strategy.
Ethics approval
Ethics approval received from the local medical ethics committee
Study design
Multicentre, randomised, single-blinded, active controlled, parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Developmental-disabilities, blood-glucose, hypoglycaemia
Intervention
In the intensive treatment arm the aim is to increase the glucose concentration above 2.5 mmol/l within three hours by increasing the carbohydrate intake by oral nutrition and/or intravenous glucose administration.
In the expectant arm the aim is to maintain the glucose concentration above 2.0 mmol/l by the usual oral nutrition protocol.
Intervention type
Drug
Phase
Not Specified
Drug names
Glucose
Primary outcome measure
Primary outcome is neurodevelopment at 18 months, assessed with the Bayley Scales of Infant Development.
Secondary outcome measures
Current secondary outcome measures as of 04/09/2019:
1. Costs for medical treatment and hospital admission until 18 months of age:
1.1 costs for diagnostic tests and treatment of the infant (glucose measurements, supplemental feeding, tube-feeding, intravenous glucose administration), and hospitalization costs for both the infant and mother
1.2 costs for medical consumption related to neurodevelopmental impairment until the age of 18 months (visits to healthcare professionals and hospital admission after the neonatal period)
2. Plasma glucose concentrations and carbohydrate intake (breastfeeding, oral or enteral feeding and intravenous glucose)
3. Frequency of treatment failure, defined as infants who become severely hypoglycaemic despite the treatment they received (frequency and severity of hypoglycaemia episodes after randomization).
Previous secondary outcome measures:
Secondary outcomes are costs for medical treatment and hospital admission until 18 months of age.
Overall trial start date
01/10/2007
Overall trial end date
01/04/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current participant inclusion criteria as 04/09/2019:
Infants greater than or equal to 35 weeks gestational age and greater than or equal to 2000 g with one of the four major risk factors for neonatal hypoglycaemia:
1. Small-for-Gestational-Age infants (SGA, birth-weight-for-gestational-age less than P10)
2. Large-for-Gestational-Age infants (LGA, birth-weight-for-gestational-age greater than P90)
3. Near-term infants 35 0/7 to 36 6/7 weeks gestational age with a birth weight greater than 2000 g
4. Infants of Diabetic Mothers (IDM)
Birth-weight-for-gestational-age is defined according to the growth charts of the Perinatale Registratie Nederland (PRN).
Previous participant inclusion criteria:
Infants greater than or equal to 35 weeks gestational age and greater than or equal to 2000 g with one of the four major risk factors for neonatal hypoglycaemia:
1. Small-for-Gestational-Age infants (SGA, birth-weight-for-gestational-age less than P10)
2. Large-for-Gestational-Age infants (LGA, birth-weight-for-gestational-age greater than P90)
3. Near-term infants 35 0/7 to 36 6/7 weeks gestational age with a birth weight greater than 2000 g
4. Infants of Diabetic Mothers (IDM)
Birth-weight-for-gestational-age is defined according to the Kloosterman growth charts.
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
800
Total final enrolment
689
Participant exclusion criteria
Current participant exclusion criteria:
Infants with serious co-morbidity will be excluded, because their co-morbidity can also affect neurodevelopment:
1. Very preterm infants (less than 34 6/7 weeks gestational age)
2. Severe perinatal asphyxia - presence of at least three of the next criteria:
2.1. Signs of intrauterine asphyxia, like late decelerations on Cardiotocogram (CTG) or meconium stained amniotic fluid
2.2. Arterial umbilical cord pH less than 7.10
2.3. Delayed initiation of spontaneous respirations greater than 5 minutes after birth
2.4. Five minute Apgar score less than 5
2.5. Multi-organ failure
3. Severe perinatal infection: requiring support of vital functions (infants without clinical signs of infection who are treated with antibiotics because of suspected perinatal infection can be included)
4. Respiratory insufficiency requiring respiratory support
5. Severe hypotension requiring vasopressor support
6. (Strong suspicion of) a syndrome or major congenital malformations
Other exclusion criteria:
7. Intravenous glucose administration before randomization
8. (Strong suspicion of) inborn error of metabolism
9. (Strong suspicion of) hyperinsulinism, except infants of diabetic mothers
10. No informed consent
Previous participant exclusion criteria:
Infants with serious co-morbidity will be excluded, because their co-morbidity can also affect neurodevelopment:
1. Very preterm infants (less than 34 6/7 weeks gestational age)
2. Severe perinatal asphyxia - presence of at least three of the next criteria:
2.1. Signs of intrauterine asphyxia, like late decelerations on Cardiotocogram (CTG) or meconium stained amniotic fluid
2.2. Arterial umbilical cord pH less than 7.10
2.3. Delayed initiation of spontaneous respirations greater than 5 minutes after birth
2.4. Five minute Apgar score less than 5
2.5. Multi-organ failure
3. Severe perinatal infection: requiring support of vital functions (infants without clinical signs of infection who are treated with antibiotics because of suspected perinatal infection can be included)
4. Respiratory insufficiency requiring respiratory support
5. Severe hypotension requiring vasopressor support
6. (Strong suspicion of) a syndrome or major congenital malformations
Other exclusion criteria:
7. (Strong suspicion of) inborn error of metabolism
8. (Strong suspicion of) hyperinsulinism, except infants of diabetic mothers
9. No informed consent
Recruitment start date
01/10/2007
Recruitment end date
01/04/2011
Locations
Countries of recruitment
Netherlands
Trial participating centre
Department of Neonatology
Amsterdam
1100 DD
Netherlands
Sponsor information
Organisation
Academic Medical Centre (AMC) (The Netherlands)
Sponsor details
Emma Children's Hospital
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
+31 (0)20 566 2131
emma@amc.uva.nl
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
The Netherlands Organisation for Health Research and Development (ZonMw) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2020 results in https://www.ncbi.nlm.nih.gov/pubmed/32023373 (added 06/02/2020)