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Trial registered on ANZCTR


Registration number
ACTRN12621001387819
Ethics application status
Approved
Date submitted
16/08/2021
Date registered
14/10/2021
Date last updated
28/09/2022
Date data sharing statement initially provided
14/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Development of small blood vessels in the kidneys of preterm infants
Scientific title
Ex utero Development of Intra-renal Vasculature in Preterm Infants from 24 weeks gestation to Term Equivalent Age
Secondary ID [1] 305056 0
None
Universal Trial Number (UTN)
Trial acronym
DIVALI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prematurity
Kidney development 323262 0
Condition category
Condition code
Renal and Urogenital 320831 320831 0 0
Normal development and function of male and female renal and urogenital system
Reproductive Health and Childbirth 320832 320832 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Exposure: preterm birth in 4 brackets of gestational age: 24 weeks, 28 weeks, 32 weeks, 36 weeks
Observations: Vascularity of kidney cortex (the study involves study participants to undergo Doppler ultrasound of kidney cortex)
Observation period: From birth to 12 months corrected age
Intervention code [1] 321453 0
Diagnosis / Prognosis
Comparator / control treatment
Term born infants
Observation: Vascularity of kidney cortex from birth to 12 months of age
Control group
Active

Outcomes
Primary outcome [1] 328629 0
Vascularity of kidney cortex (defined as ratio of vascular structures and non-vascularized tissue on a very low flow doppler ultrasound image (SMI=Superb microvascular imaging mode))
Timepoint [1] 328629 0
Term (corrected) age and 12 months of age
Secondary outcome [1] 399758 0
Renal structure (kidney length and cortical thickness by conventional 2D ultraound)
Timepoint [1] 399758 0
Term (corrected) age and 12 months of age
Secondary outcome [2] 401047 0
Renal function, composite outcome from
- serum creatinine (Jaffé assay)
- eGFR (calculated by serum creatinine, anthropometry of study participant and factor for either premature or term birth)
- albuminuria (albumine/creatinine ratio in spot urine)
- blood pressure (non invasive measurement via BP cuff)
Timepoint [2] 401047 0
Term (corrected) age and 12 months of age

Eligibility
Key inclusion criteria
Preterm infant born in one of the 4 gestational age groups:
Group 1: 24 gestational weeks
Group 2: 28 gestational weeks
Group 3: 32 gestational weeks
Group 4: 36 gestational weeks
Group 5 (control group): 39-40 gestational weeks
Minimum age
0 Hours
Maximum age
72 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Antenatally detected congenital abnormality of the kidneys or urinary tract, including:
o Underdevelopment or absence of one or both kidney
o Horseshoe kidney or fused kidneys
o One or more intrarenal cysts
o Duplex kidney or duplicated collecting system
o Hydronephrosis, ureteropelvic junction obstruction, megaureter
o Posterior urethral valves
o Any abnormality of the kidney or urogenital system or associated condition with the potential to affect the normal renal development
- If one of the above conditions are not known at the time of enrolment, but diagnosed with the first assessment at less than 72 hours after birth, the infant will be excluded from the study and referred for specialist assessment and management.
- Moribund infant who is not expected to survive beyond the first scheduled study assessment.


Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample size: Assumption (from previously published data): reduction of 10% in vascularisation in the kidney cortex between preterm and term born infants as the minimal clinically important difference (MCID) resulting in long term alteration of renal function and blood pressure regulation. Preliminary data estimate: proportion of vasculature within the cortex of infants at 44%, with a standard deviation of 6.7%. Sample size of 14 per group will be required to demonstrate a 10% difference in this proportion ( with alpha 0.05, power 80%).
Statistical analysis: For all analyses, the level of statistical significance (two-sided) is 0.05. Correction for multiple testing will be used where applicable. All statistics will include appropriate measures of uncertainty for inferential statistics, such as standard error or 95% confidence intervals.
Patient characteristics and outcomes per group as mean with standard deviation (SD) or median with interquartile range (IQR), depending on distribution of data. Normality of the data will be assessed with graphical methods (Q-Q plots and histograms) and tests of univariate normality (e.g. Shapiro-Wilkins test). Differences between group means will be analysed using ANOVA, and differences between group medians by Kruskal-Wallis test. Dichotomous data will be presented in proportions. Chi-Square test and Fisher’s exact test will be used to analyse differences between group proportions.
The primary outcome of cortical vascular development for all assessments over time will be analyzed by repeated measures regression model for each group separately. For group 1,2 and 3 (study participants born <36 weeks gestational age), the primary outcome at 40 weeks postmenstrual age will be correlated to covariates of perinatal and neonatal morbidities using multivariable regression models. For all groups, the primary outcome at 12 months of age will additionally be correlated to morbidities and treatments in the interval between assessment W40 and assessment Y1 using multivariable regression models.
Secondary outcomes of serum creatinine, eGFR, albuminuria, blood pressure, kidney length, cortical thickness on ultrasound at 40 weeks postmenstrual age and 12 months of age for all groups will be correlated with the primary outcome of the same assessment using correlation coefficients (Pearson r)

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/10/2021
Actual
23/10/2021
Date of last participant enrolment
Anticipated
14/10/2023
Actual
Date of last data collection
Anticipated
14/10/2024
Actual
Sample size
Target
70
Accrual to date
25
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20252 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 34991 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 309452 0
Charities/Societies/Foundations
Name [1] 309452 0
Ramsay Reserach and Teaching Fund Scheme
Country [1] 309452 0
Australia
Primary sponsor type
Individual
Name
Dr Eveline Staub
Address
Department of Neonatology
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 310420 0
None
Name [1] 310420 0
Address [1] 310420 0
Country [1] 310420 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309245 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 309245 0
Level 13 Kolling Building
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Ethics committee country [1] 309245 0
Australia
Date submitted for ethics approval [1] 309245 0
18/02/2021
Approval date [1] 309245 0
23/03/2021
Ethics approval number [1] 309245 0
2021/ETH00082

Summary
Brief summary
This study will characterize the development of the small blood vessels in the outermost layer of the kidney after very preterm birth (as early as 24 of 40 weeks of pregnancy) to term and to one year of age, using a new ultrasound mode with the ability to demonstrate blood flow in very small blood vessels (SMI ultrasound). The study will also compare the findings of the blood vessel development with measurements traditionally used to measure the function of the kidneys.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113474 0
Dr Eveline Staub
Address 113474 0
Department of Neonatology
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Country 113474 0
Australia
Phone 113474 0
+61 2 9463 2186
Fax 113474 0
Email 113474 0
[email protected]
Contact person for public queries
Name 113475 0
Eveline Staub
Address 113475 0
Department of Neonatology
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Country 113475 0
Australia
Phone 113475 0
+61 2 9463 2186
Fax 113475 0
Email 113475 0
[email protected]
Contact person for scientific queries
Name 113476 0
Eveline Staub
Address 113476 0
Department of Neonatology
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Country 113476 0
Australia
Phone 113476 0
+61 2 9463 2186
Fax 113476 0
Email 113476 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in the publication after de-identification (text, tables, figures and appendices)
When will data be available (start and end dates)?
12 months after publication of results, no end date.
Available to whom?
To future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept NSW Health/NSLHD conditions for access according to the Data Sharing Accord.
Available for what types of analyses?
To achieve the aims in the approved proposal and for IPD meta-analyses
How or where can data be obtained?
Researchers can apply for access to the data deposited in the digital research data respository of the Australian Data Archive by emailing the PI ([email protected]) a research proposal approved by an independent ethics committee and in accordance with the NSW health/NSLDH conditions for access according to the Data Sharing Accord.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12896Study protocol  [email protected] Study protocol will be uploaded into the digital r... [More Details]
12897Statistical analysis plan  [email protected] Study protocol will be uploaded into the digital r... [More Details]



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.