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Trial registered on ANZCTR
Registration number
ACTRN12624001025527
Ethics application status
Approved
Date submitted
12/06/2024
Date registered
23/08/2024
Date last updated
5/10/2024
Date data sharing statement initially provided
23/08/2024
Type of registration
Prospectively registered
Titles & IDs
Public title
Redefining Glucose thresholds for Hypo Treatment in Children with Type 1 Diabetes on Closed loop Therapy
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Scientific title
Redefining Glucose Thresholds for Hypoglycaemia Management in Children with Type 1 Diabetes on Closed Loop Therapy: A Cross-over Clinical Trial
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Secondary ID [1]
312269
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Nil known
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes
333985
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Condition category
Condition code
Metabolic and Endocrine
330650
330650
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0
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Diabetes
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Public Health
330818
330818
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0
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Health service research
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
The study aims to determine if reducing the cut-off of initiating treatment will be an acceptable hypoglycaemia threshold and will not be associated with an increase in time spent in hypoglycaemia <3.0 mmol/L with worsening of glycaemic outcomes.
A two-treatment, two-period cross-over randomised controlled non-inferiority trial design will be used. Participants will be randomised to sequence A (‘Standard Hypo Rx First’), or sequence B (‘Revised Hypo Rx First’).
‘Standard Hypo Rx First’ participants will use the standard hypo treatment (i.e. Hypoglycaemia treatment initiated with glucose level <3.9 mmol/L) for 4 weeks (Period 1) after which they will switch to revised hypo treatment plan for 4 weeks (Hypoglycaemia treatment initiated at lower revised threshold of less than or equal to 3.6 mmol/L) (Period 2). The revised hypo treatment plan will consist of the same hypo treatment as clinically recommended (i.e. 10-15g of fast-acting carbohydrates, or 5.0-7.5g of fast-acting carbohydrates if on closed loop therapy) and does not change between the two arms.
‘Revised Hypo Rx First’ participants will start with revised hypo treatment plan for 4 weeks (Period 1) and cross over to standard hypo Rx plan for 4 weeks (Period 2). The 4-week duration is chosen to capture adequate number of hypoglycaemic episodes. Most children are expected to experience at least 2 or more episodes per week.
There will be a wash-out phase of at least 2 weeks to prevent carryover effects.
Participants will be randomised to one of the two treatment sequences using https://sealedenvelope.com/ into a) Standard Hypo Rx First’ or b) Revised Hypo Rx First’.
All participants will receive weekly review with email/phone calls by our team to ensure adherence and address any concerns or questions participants may have. If time spent <3.0 mmol/L has doubled from baseline and/or is >1%, research staff (doctor and research diabetes educator) will review the participant to ensure 1) if they are ‘true’ hypoglycaemic events 2) explore the reason if ‘true’ hypoglycaemic.
Adherence to hypo management will be monitored using a participant Logbook that asks for the date and time the hypo occurred, the glucose level (in mmol/L), the amount of carbohydrates given as treatment, and whether they are in the revised or standard treatment plan arms at the time of the hypo occurring.
Potential participants will be identified from the Western Australian Children’s Diabetes Database by a Child and Adolescent Health Service employee and invited via email to partake in this study. Participants must attend the Diabetes Clinics at Perth Children’s Hospital to be eligible.
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Intervention code [1]
328726
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Treatment: Other
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Comparator / control treatment
As this is a cross-over randomised control study, the intervention participants will be their own control. The ‘Standard Hypo Rx First’ arm/study period will be acting as the control/comparator.
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Control group
Active
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Outcomes
Primary outcome [1]
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Time spent in hypoglycaemia <3.0 mmol/l
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Assessment method [1]
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Continuous Glucose Monitoring (CGM)
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Timepoint [1]
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During the 10-week period (4 weeks intervention, 2 weeks washout, 4 weeks standard)
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Secondary outcome [1]
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Time in range 3.9-10.0 mmol/l
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Assessment method [1]
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Continuous Glucose Monitoring (CGM)
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Timepoint [1]
436048
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During the 10-week period (4 weeks intervention, 2 weeks washout, 4 weeks standard)
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Secondary outcome [2]
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Time spent in hyperglycaemia >10.0 mmol/l
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Assessment method [2]
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Continuous Glucose Monitoring (CGM)
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Timepoint [2]
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During the 10-week period (4 weeks intervention, 2 weeks washout, 4 weeks standard)
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Secondary outcome [3]
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Time spent in hyperglycaemia >13.9 mmol/l
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Assessment method [3]
436050
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Continuous Glucose Monitoring (CGM)
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Timepoint [3]
436050
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During the 10-week period (4 weeks intervention, 2 weeks washout, 4 weeks standard)
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Secondary outcome [4]
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Participant’s acceptability of revised hypoglycaemia cut-off
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Assessment method [4]
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Open-ended questions in semi-structured interview (Telehealth), conducted by a clinical diabetes nurse educator who is qualified to undertake qualitative research. These interviews will take approximately 30 minutes, and will be audio-recorded for transcription.
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Timepoint [4]
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At the end of the 10 weeks of study participation
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Eligibility
Key inclusion criteria
1. Diagnosis of Type 1 diabetes
2. 6 to 18 years
3. Duration of diabetes of >12 months
4. On advanced closed loop therapy
4.1 for at least 4 weeks and
4.2 using the system optimally for >80% in last 2 weeks.
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Minimum age
6
Years
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Maximum age
18
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Impaired hypoglycaemia awareness. Self-reported Gold score greater than or equal to 4 (these patients need higher glucose targets). For young children (age 6 to 10 years or if the child is developmentally young to self-report), parent-reported response will be used.
2. Increased time spent in hypoglycaemia as documented on CGM (>2% of time spent <3.0 mmol/L and/or >6% of time spent <3.9 mmol/L) for last two weeks
3. Families not willing to try lower cut-off due to fear of hypoglycaemia.
4. Severe hypoglycaemia (coma, convulsion or altered consciousness requiring third party assistance) in last 12 months.
5. Any medical or psychological disease state of the child and/or caregiver that limits capacity to participate in the study.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised to one of the two treatment sequences using https://sealedenvelope.com/ into a) 'Standard Hypo Rx First’ or b) 'Revised Hypo Rx First’.
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Crossover
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Other design features
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Phase
Not Applicable
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Type of endpoint/s
Safety/efficacy
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Statistical methods / analysis
A non-inferiority limit was identified based on discussions with clinicians and was set at a 75% increase in time spent in hypoglycaemia. This equates to a difference of 0.56 in the log-transformed time <3.0 mmol/L.
A sample of 36 participants would provide over 90% power for the boundary of a one-sided 97.5% confidence interval (one sided alpha of 0.025) to fall below the non-inferiority limit of 0.56. Allowing for 10% drop-out, we will recruit 40 participants.
The primary analysis will assess the difference in time spent in clinically significant hypoglycaemia (<3.0 mmol/L) between the ‘standard hypo Rx’ and ‘revised hypo Rx’ conditions measured over four weeks. A linear mixed model including terms for treatment, period and sequence will be conducted on the log-transformation of ‘time spent < 3.0 mmol/L’. The ‘treatment’ effect along with 95% confidence intervals will be produced. To demonstrate non-inferiority, the lower limit of the one-sided 95% confidence interval must fall below the pre-specified non-inferiority limit.
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Recruitment
Recruitment status
Not yet recruiting
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Date of first participant enrolment
Anticipated
21/10/2024
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Actual
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Date of last participant enrolment
Anticipated
30/04/2025
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Actual
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Date of last data collection
Anticipated
31/07/2025
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Actual
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Sample size
Target
40
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
WA
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Recruitment hospital [1]
26664
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Perth Children's Hospital - Nedlands
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Recruitment postcode(s) [1]
42703
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6009 - Nedlands
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Funding & Sponsors
Funding source category [1]
316654
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Charities/Societies/Foundations
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Name [1]
316654
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Perth Children's Hospital Foundation
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Address [1]
316654
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Country [1]
316654
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Australia
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Primary sponsor type
Hospital
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Name
Perth Children's Hospital
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Address
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Country
Australia
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Secondary sponsor category [1]
318906
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None
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Name [1]
318906
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Address [1]
318906
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Country [1]
318906
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
315433
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Child and Adolescent Health Service Human Research Ethics Committee
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Ethics committee address [1]
315433
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CAHS.Ethics@health.wa.gov.au
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Ethics committee country [1]
315433
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Australia
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Date submitted for ethics approval [1]
315433
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28/11/2023
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Approval date [1]
315433
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29/11/2023
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Ethics approval number [1]
315433
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RGS0000006405
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Summary
Brief summary
Hypoglycaemia (hypo) education is provided at the time of type 1 diabetes diagnosis and knowledge reviewed in the clinic as required. The current threshold for initiating hypo treatment at glucose level < 3.9 mmol/L is on expert opinion, rather than evidence based, which was chosen to avoid glucose levels from dropping even further (<3.0 mmol/L), considered as significant hypoglycaemia below which neurocognitive decline occurs. However, it needs to be appreciated that levels between 3.0 and 3.9 mmol/L are considered as normal in healthy individuals with no diabetes. With the availability of continuous glucose monitoring (CGM) and closed loop therapy as standard care in management of T1D, there is ability to support lower glucose thresholds for treatment as basal insulin delivery is suspended with prediction of a hypo. This will avoid overtreatment of hypos and resultant high glucose levels. The study aims to determine if reducing the cut-off of initiating treatment will be an acceptable hypo threshold and will not be associated with an increase in time spent in hypos <3.0 mmol/L with worsening of glycaemic outcomes.
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Dr Mary Abraham
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Address
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Perth Children's Hospital, 15 Hospital Avenue, Nedlands, WA 6009
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Country
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Australia
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Phone
134686
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+61 8 6456 5027
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Fax
134686
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Email
134686
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[email protected]
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Contact person for public queries
Name
134687
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Dr Mary Abraham
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Address
134687
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Perth Children's Hospital, 15 Hospital Avenue, Nedlands, WA 6009
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Country
134687
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Australia
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Phone
134687
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+61 8 6456 5027
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Fax
134687
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Email
134687
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[email protected]
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Contact person for scientific queries
Name
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Dr Mary Abraham
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Address
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Perth Children's Hospital, 15 Hospital Avenue, Nedlands, WA 6009
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Country
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Australia
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Phone
134688
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+61 8 6456 5027
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Fax
134688
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Email
134688
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[email protected]
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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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.
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