Condition category
Pregnancy and Childbirth
Date applied
23/08/2007
Date assigned
23/08/2007
Last edited
06/02/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results

Plain English Summary

Not provided at time of registration

Trial website

http://www.studies-obsgyn.nl/hypoexit.nl

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

http://www.amc.uva.nl/

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)

Publication citations

Additional files

Editorial Notes

06/02/2020: The following changes were made to the trial record: 1. Publication reference added. 2. The total final enrolment was added. 04/09/2019: The following changes were made to the trial record: 1. The recruitment end date was changed from 01/10/2010 to 01/04/2011. 2. The overall end date was changed from 01/10/2010 to 01/04/2013. 3. The secondary outcome measures were changed. 4. The inclusion criteria were changed. 5. The exclusion criteria were changed.