Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001473358
Ethics application status
Approved
Date submitted
29/09/2017
Date registered
18/10/2017
Date last updated
7/02/2019
Date data sharing statement initially provided
7/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Treating hypoglycaemia in newborns with Glucagon And Diazoxide: The Glad Study
Scientific title
A randomized, controlled trial to evaluate the effect of Diazoxide and Glucagon for the treatment of significant hypoglycaemia in neonates: The GLAD study
Secondary ID [1] 292981 0
Nil known
Universal Trial Number (UTN)
U1111-1202-7735
Trial acronym
GLAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypoglycaemia 304884 0
Infant of diabetic mother 304885 0
Condition category
Condition code
Reproductive Health and Childbirth 304200 304200 0 0
Complications of newborn
Metabolic and Endocrine 304201 304201 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diazoxide – 5mg/kg/dose 8 hourly orally.
Treatment algorithm will be used to maintain treatment fidelity, with increases and decreases in glucose and medications based on blood glucose level (BGL)
Fluids or Diazoxide will be titrated down (by 1mg/kg) if BGL is 5.0mmol/L.
Treatment will continue until Diazoxide is no longer required; OR if BGLs not maintained at 3.5 mmol/L or more in spite of maximal therapy; OR at 48 hours; OR at discretion of clinician (with reason to be documented). After this point, further management is at the discretion of the clinician and may involve increased concentration glucose infusion or use of glucagon.
Adherence with treatment algorithm will be monitored by investigators. The case notes of all enrolled patients will be screened for adherence by research nurse/investigators.
Intervention code [1] 299222 0
Treatment: Drugs
Comparator / control treatment
Glucagon – 10microgram/kg/hr continuous intravenous infusion. For up to 48 hours.
Glucagon will be titrated up to a maximum of 20microgram/kg/hr if blood glucose level is less than 3.5mmol/L. Glucagon will be titrated down (by half each time) if BGL is 5.0mmol/L or more.
Treatment algorithm will be used to maintain treatment fidelity, with increases and decreases in glucose and medications based on blood glucose level (BGL)
Treatment will continue until Glucagon is no longer required; OR if BGLs not maintained at 3.5 mmol/L or more in spite of maximal therapy; OR at 48 hours; OR at discretion of clinician (with reason to be documented). After this point, further management is at the discretion of the clinician and may involve increased concentration glucose infusion or use of diazoxide.
Adherence with treatment algorithm will be monitored by investigators. The case notes of all enrolled patients will be screened for adherence by research nurse/investigators.
Control group
Active

Outcomes
Primary outcome [1] 303503 0
Treatment failure in allocated study arm defined as:
• requirement for continuous intravenous glucose infusion with >10% glucose to maintain blood glucose measurement more than or equal to 3.5mmol/l
• and/or failure to obtain central venous access if required
• and/or additional therapies (Diazoxide/Glucagon) required

All blood glucose concentrations will be analysed by the gold standard glucose oxidase method by a combined metabolite/ blood gas analyser (e.g. ABL 700, Radiometer Ltd, Copenhagen, Denmark).
Timepoint [1] 303503 0
within 48 hours of treatment commencement.
Secondary outcome [1] 339102 0
Proportion of participants with a reduction in serum sodium to less than 132 mmol/L
Timepoint [1] 339102 0
In the first 24 hours after commencement of treatment
Secondary outcome [2] 339104 0
Duration of use of peripheral central venous catheter for glucose administration
Timepoint [2] 339104 0
1 week after commencement of treatment
Secondary outcome [3] 339105 0
Change in weight
Timepoint [3] 339105 0
24 hours after treatment commencement
Secondary outcome [4] 339106 0
Number of hypoglycaemic episodes (defined as a BGL of less than 3.5mmol/l)
Timepoint [4] 339106 0
within 48 hours of treatment commencement
Secondary outcome [5] 339107 0
Length of stay in the nursery
Timepoint [5] 339107 0
Within 1 week of treatment commencement
Secondary outcome [6] 339666 0
Cost effectiveness of each treatment. A health economist will assess this outcome based on such measures as length of nursery stay, duration of treatment and relative cost of treatments.
Timepoint [6] 339666 0
2 weeks

Eligibility
Key inclusion criteria
Infants of diabetic mothers (any type of diabetes) who satisfy ALL of the following:
1. more than or equal to 35 weeks gestation
2. Birth-weight more than 2.2 kg
3. Less than 12 hours old
4. Unlikely to require admission to NICU for any other reason e.g. respiratory distress
5. Diagnosis of neonatal hypoglycaemia with 10% Glucose infusion rate 90ml/kg/day and BGL less than 3.5mmol/L
Minimum age
No limit
Maximum age
12 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Major congenital abnormalities

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data analysis
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.

Economic evaluation
The cost-effectiveness of Diazoxide to prevent primary treatment failure will be compared with glucagon within the period to discharge. Resource utilisation will be obtained from a clinical record form identifying both length of stay (LOS) and relevant Diagnostic Related Group (DRG) code for the mother, plus any subsequent operative procedure (DRG), respiratory problem requiring treatment (DRG), and NICU admission for the baby (plus LOS). Costs will be assessed using Australian Department of Health cost weights and purchase unit prices.

Power and sample size
Typically, 50% of term infants of mothers with diabetes (gestational or insulin dependent) will be diagnosed as hypoglycaemic in our institution. Assuming a similar 10% rate of admission to NICU for intensive treatment this would still result in 90 nursery admissions per year. In 2015-16 42 infants were prescribed Diazoxide for the management hypoglycaemia. We predict a 25% reduction in the rate of treatment failure in the Diazoxide arm of the study. This will require 100 infants who meet the eligibility criteria and a recruitment period of 2 years.
No head to head trial has been previously undertaken and there is no data on the effectiveness of either medication for this outcome. As such, a more pragmatic approach has been taken based on both clinical experience and available trial information. The authors propose the current trial size as a representative sample, being similar to the annual experience in our centre. We will recalculate sample size after enrollment of the first 25 babies.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
6/11/2017
Actual
12/02/2018
Date of last participant enrolment
Anticipated
12/02/2020
Actual
Date of last data collection
Anticipated
12/03/2020
Actual
Sample size
Target
100
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 9112 0
Womens and Childrens Hospital - North Adelaide
Recruitment postcode(s) [1] 17612 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 297606 0
Hospital
Name [1] 297606 0
Department of Perinatal Medicine, Women's and Children's Hospital
Country [1] 297606 0
Australia
Primary sponsor type
Individual
Name
Dr Lydia Kennedy
Address
Department of Perinatal Medicine,
Women's and Children's Hospital
72 King William Street
North Adelaide SA 5006
Country
Australia
Secondary sponsor category [1] 296620 0
Individual
Name [1] 296620 0
Dr Michael Stark
Address [1] 296620 0
Department of Perinatal Medicine,
Women's and Children's Hospital
72 King William Street
North Adelaide SA 5006
Country [1] 296620 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298699 0
Women's and Children's Human Research Ethics Committee
Ethics committee address [1] 298699 0
Ethics committee country [1] 298699 0
Australia
Date submitted for ethics approval [1] 298699 0
06/06/2017
Approval date [1] 298699 0
17/10/2017
Ethics approval number [1] 298699 0
HREC/17/WCHN/99

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2089 2089 0 0
/AnzctrAttachments/373719-The GLAD study protocol for CTR.pdf (Protocol)

Contacts
Principal investigator
Name 77934 0
Dr Lydia Kennedy
Address 77934 0
Department of Perinatal Medicine
Women's and Children's Hospital
72 King William Street
North Adelaide SA 5006
Country 77934 0
Australia
Phone 77934 0
+61 8 81617631
Fax 77934 0
+61 8 81617654
Email 77934 0
[email protected]
Contact person for public queries
Name 77935 0
Lydia Kennedy
Address 77935 0
Department of Perinatal Medicine
Women's and Children's Hospital
72 King William Street
North Adelaide SA 5006
Country 77935 0
Australia
Phone 77935 0
+61 8 81617631
Fax 77935 0
+61 8 81617654
Email 77935 0
[email protected]
Contact person for scientific queries
Name 77936 0
Lydia Kennedy
Address 77936 0
Department of Perinatal Medicine
Women's and Children's Hospital
72 King William Street
North Adelaide SA 5006
Country 77936 0
Australia
Phone 77936 0
+61 8 81617631
Fax 77936 0
+61 8 81617654
Email 77936 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not in original study protocol.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.