Neurodevelopmental outcome after neonatal hypoglycaemia: a multi-centre randomised controlled trial comparing intensive treatment versus expectant glucose monitoring in 'high risk' newborns
| ISRCTN | ISRCTN79705768 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN79705768 |
| Secondary identifying numbers | ZonMW Doelmatigheid 80-007022-98-07406 |
- Submission date
- 23/08/2007
- Registration date
- 23/08/2007
- Last edited
- 06/02/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Ms Debbie Nuytemans
Scientific
Scientific
Department of Neonatology
Emma Children's Hospital
Academic Medical Centre (AMC)
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
| Phone | +31 (0)20 566 3477 |
|---|---|
| HYPO-EXIT@AMC.nl |
Study information
| Study design | Multicentre, randomised, single-blinded, active controlled, parallel group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | Neurodevelopmental outcome after neonatal hypoglycaemia: a multi-centre randomised controlled trial comparing intensive treatment versus expectant glucose monitoring in 'high risk' newborns |
| Study acronym | HYPO-EXIT |
| Study objectives | 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(s) | Ethics approval received from the local medical ethics committee |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/10/2007 |
| Completion date | 01/04/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | 800 |
| Total final enrolment | 689 |
| Key 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. |
| Key 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 |
| Date of first enrolment | 01/10/2007 |
| Date of final enrolment | 01/04/2011 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Department of Neonatology
Amsterdam
1100 DD
Netherlands
1100 DD
Netherlands
Sponsor information
Academic Medical Centre (AMC) (The Netherlands)
Hospital/treatment centre
Hospital/treatment centre
Emma Children's Hospital
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
| Phone | +31 (0)20 566 2131 |
|---|---|
| emma@amc.uva.nl | |
| Website | http://www.amc.uva.nl/ |
"ROR" |
https://ror.org/03t4gr691 |
Funders
Funder type
Research organisation
The Netherlands Organisation for Health Research and Development (ZonMw) (The Netherlands)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 06/02/2020 | 06/02/2020 | Yes | No |
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.
