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Trial registered on ANZCTR


Trial ID
ACTRN12614001263684
Ethics application status
Approved
Date submitted
17/11/2014
Date registered
3/12/2014
Date last updated
19/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
hPOD - Hypoglycaemia Prevention in newborns with Oral Dextrose
Scientific title
In newborn infants at risk of hypoglycaemia does prophylactic oral dextrose gel compared to placebo reduce admission to Newborn Intensive Care Unit (NICU).
Secondary ID [1] 285597 0
NIL
Universal Trial Number (UTN)
U1111-1158-0852
Trial acronym
hPOD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neonatal Hypoglycaemia 293439 0
Condition category
Condition code
Metabolic and Endocrine 293711 293711 0 0
Other metabolic disorders
Reproductive Health and Childbirth 293712 293712 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
40% dextrose gel.

Dose of 200mg/kg (0.5ml/kg), given at 1 hour of age, followed by breastfeed. Administered by massage into the buccal mucosa.

The dose of 40% dextrose gel in this trial has been informed by the pre-hPOD dosage trial (ACTRN12613000322730).
Intervention code [1] 290547 0
Prevention
Comparator / control treatment
Placebo - 2% hydroxymethylcellulose gel.

0.5ml/kg, given at 1 hour of age, followed by breastfeed. Administered by massage into the buccal mucosa.
Control group
Placebo

Outcomes
Primary outcome [1] 293519 0
Admission to NICU, defined as admission to Neonatal Intensive Care Unit (NICU), or Special Care Baby Unit (SCBU) for the hospitals which use that name, for > 4 hours, determined from medical records.
Timepoint [1] 293519 0
Prior to discharge home.
Secondary outcome [1] 311237 0
Incidence of neonatal hypoglycaemia (any blood glucose concentration <2.6mM measured by the glucose oxidase method).
Timepoint [1] 311237 0
In the first 48 hours after birth.
Secondary outcome [2] 311239 0
Hyperglycaemia (any blood glucose concentration of > 10mmol/l measured by the glucose oxidase method).
Timepoint [2] 311239 0
In the first 48 hours after birth.
Secondary outcome [3] 311240 0
Breastfeeding (full or exclusive), determined by parental questionnaire.
Timepoint [3] 311240 0
At discharge home.
Secondary outcome [4] 311241 0
Received any formula prior to discharge from hospital.
Timepoint [4] 311241 0
At discharge home.
Secondary outcome [5] 311242 0
Formula feeding at 6 weeks after birth, determined by parental questionnaire.
Timepoint [5] 311242 0
At 6 weeks after birth.
Secondary outcome [6] 311243 0
Economic cost of healthcare to primary discharge from hospital, determined using resource utilisation data from clinical records.
Timepoint [6] 311243 0
At discharge home.
Secondary outcome [7] 311244 0
Maternal satisfaction, determined by parental questionnaire.
Timepoint [7] 311244 0
At 6 weeks after birth.
Secondary outcome [8] 311245 0
Neurosensory disability, defined as any of: legal blindness; sensorineural deafness requiring hearing aids; cerebral palsy; Bayley Scale of Infant Development Version III cognitive, language or motor score lower than one standard deviation below the mean, at 2 years' corrected age.
Timepoint [8] 311245 0
At 2 years' corrected age.

Eligibility
Key inclusion criteria
Babies who are at risk of hypoglycaemia, defined as satisfying AT LEAST ONE of the following:

1. Infants of diabetic mothers (any type of diabetes)
2. Preterm (< 37 weeks' gestation)
3. Small (< 2.5kg or < 10th centile on population or customised birthweight chart)
4. Large (> 4.5kg or > 90th centile on population or customised birthweight chart)

AND satisfy ALL of the following:

1. > or = 35+0 weeks' gestation
2. Birthweight > or = 2.2kg
3. < 1 hour old
4. No apparent indication for NICU/SCBU admission at time of randomisation
5. Unlikely to require admission to NICU/SCBU for any other reason e.g. respiratory distress
6. Mother intending to breastfeed
Minimum age
0 Hours
Maximum age
1 Hours
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Major congenital abnormality
2. Previous formula feed or intravenous fluids
3. Previous diagnosis of hypoglycaemia
4. Admitted to NICU/SCBU
5. Imminent admission to NICU/SCBU

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Enrolling: Parents of babies who are likely to become eligible (maternal diabetes, likely late preterm birth, or anticipated high or low birthweight) will be identified through lead maternity carers and antenatal clinics and provided with an information sheet as early as is feasible. Written informed consent will normally be obtained before birth by the lead maternity carer or a member of the clinical team.

Treatment allocation: Allocation to intervention will be by central randomisation by computer, which will prescribe the treatment pack number to be used and volume of gel to be given. The intervention and placebo gels look identical and are packaged identically.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Within each hospital and stratum babies will be randomized to placebo or dextrose within fixed block sizes using the Plan procedures of SAS (v9.4 SAS Institute Inc). Seeds for the pseudorandom number generator were chosen from successive random numbers in ETON Statistical and Math Tables (4th Ed. Eton Press Ltd).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Power and Sample Size
Based on data from Auckland City Hospital and Waikato Hospital, 10% of at-risk babies will require admission to NICU. A trial of 2,129 babies (1,014 in each arm, with continuity correction and allowing for 5% drop-out rate), will have 90% power to detect a 40% relative reduction (absolute reduction of 4%) in admission to NICU from 10% to 6% with two-sided alpha of 0.05.

Minimum Important Difference
Apart from any cost implications, any reduction in NICU admission would be an important benefit to both patients and clinicians. NICU admission involves separation of mother and baby at a crucial stage in their relationship 28, potentially disrupts the establishment of breast-feeding and involves painful procedures. Moreover, NICU cots are often in short supply due to the increasing incidence of risk factors for admission, such as preterm births and maternal diabetes. Any intervention that reduced NICU admission would be welcomed by clinicians as this will make it less likely that critically unwell babies will need to be transferred to a NICU in another city that has cots available.
Should this study show that dextrose gel is effective at preventing NICU admission, it will also be critical to find out if this improves long-term outcomes for babies. Our own preliminary data in 138 2-year-old Waikato children born at risk of hypoglycaemia show that 40% have evidence of developmental delay. A sample size of 2028 babies would allow us to detect a reduction in the number of children with one or more low developmental scores (more than 1SD below the mean) on Bayley Scales of Infant Development Edition III assessment at 2 years of age from 40% to 33%. Thus, if this trial is successful, we will have adequate power to investigate further these long-term outcomes in the future.

Analyses
The primary outcome of NICU admission will be analysed by logistic regression, stratifying by collaborating centre. Secondary analyses will adjust for potentially confounding variables: reason for risk of hypoglycaemia (infant of diabetic, late preterm, small, large, and other), sex, gestational age, and mode of birth (vaginal vs caesarean section). Continuous data will be compared by Student’s t test, or the Mann-Whitney U test if the data are not normally distributed and cannot be converted to near-normality by simple transformation. Data with repeated points, such as blood glucose concentrations, will be compared using mixed model techniques, modelling the main effect of treatment group allocation, time and their interaction, with significant main effects and interactions tested using the method of Tukey. All tests will be two-tailed, with P<0.05 considered significant. The data will be analysed on an intention-to-treat basis, and any baby who dies or for whom admission to NICU is unable to be verified (e.g. through maternal withdrawal of consent for ascertainment of NICU admission status) will be assigned the worst case outcome of NICU admission.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 7184 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [2] 9616 0
The Townsville Hospital - Douglas
Recruitment hospital [3] 9617 0
Mackay Base Hospital - Mackay
Recruitment postcode(s) [1] 14946 0
5006 - North Adelaide
Recruitment postcode(s) [2] 18372 0
4814 - Douglas
Recruitment postcode(s) [3] 18373 0
4740 - Mackay
Recruitment outside Australia
Country [1] 6454 0
New Zealand
State/province [1] 6454 0
Auckland, Whangarei, Waikato, Hawkes Bay, Tauranga, Whakatane, Southland

Funding & Sponsors
Funding source category [1] 290194 0
Government body
Name [1] 290194 0
Health Research Council of New Zealand
Address [1] 290194 0
PO Box 5541
Wellesley Street
Auckland 1141
Country [1] 290194 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
The University of Auckland
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 288904 0
None
Name [1] 288904 0
Address [1] 288904 0
Country [1] 288904 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291905 0
Health and Disability Ethics Committees
Ethics committee address [1] 291905 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6011
Ethics committee country [1] 291905 0
New Zealand
Date submitted for ethics approval [1] 291905 0
Approval date [1] 291905 0
15/02/2013
Ethics approval number [1] 291905 0
13/NTA/8
Ethics committee name [2] 299264 0
Women's and Children's Network Research Ethics Committee
Ethics committee address [2] 299264 0
Level 2, Samuel Way Building
72 King William Road
North Adelaide SA 5006
Ethics committee country [2] 299264 0
Australia
Date submitted for ethics approval [2] 299264 0
27/05/2016
Approval date [2] 299264 0
18/08/2016
Ethics approval number [2] 299264 0
HREC/16/WCHN/86

Summary
Brief summary
Hypoglycaemia is the commonest metabolic condition of the newborn. It affects up to 15% of babies, and the incidence is increasing as risk factors such as maternal diabetes and preterm birth are becoming more common. Neonatal hypoglycaemia frequently leads to neonatal intensive care unit (NICU) admission and may cause long-term brain damage. There currently are no evidence-based strategies to prevent hypoglycaemia and its adverse consequences.

The purpose of this trial is to determine whether prophylactic dextrose gel prevents admission to NICU.
Trial website
http://www.liggins.auckland.ac.nz/en/about/research-themes/life-path_1/clinical-research-1_1/hpod-study.html
Trial related presentations / publications
Hegarty, J.E, Harding, J.E, Gamble, G.D, Crowther, C.A, Edlin, R.P, Alsweiler, J.M. (2016). Oral Dextrose Gel to Prevent Neonatal Hypoglycaemia in Newborn Babies at Risk: a Randomised Controlled Dose-Finding Trial (The pre-hPOD Study). PLoS Medicine (on-line).http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002155
Public notes

Contacts
Principal investigator
Name 52502 0
Prof Jane Harding
Address 52502 0
Liggins Institute
University of Auckland
Private Bag 92019
Auckland 1142
Country 52502 0
New Zealand
Phone 52502 0
+6493737599 ext 86439
Fax 52502 0
Email 52502 0
j.harding@auckland.ac.nz
Contact person for public queries
Name 52503 0
Prof Jane Harding
Address 52503 0
Liggins Institute
University of Auckland
Private Bag 92019
Auckland 1142
Country 52503 0
New Zealand
Phone 52503 0
+6493737599 ext 86439
Fax 52503 0
Email 52503 0
j.harding@auckland.ac.nz
Contact person for scientific queries
Name 52504 0
Prof Jane Harding
Address 52504 0
Liggins Institute
University of Auckland
Private Bag 92019
Auckland 1142
Country 52504 0
New Zealand
Phone 52504 0
+6493737599 ext 86439
Fax 52504 0
Email 52504 0
j.harding@auckland.ac.nz