Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001084875
Ethics application status
Approved
Date submitted
9/10/2012
Date registered
10/10/2012
Date last updated
13/07/2022
Date data sharing statement initially provided
1/07/2019
Date results information initially provided
1/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The ProVIDe Study. The effect of higher intravenous protein intake for extremely low birthweight babies in the first week after birth on survival free from neurodevelopmental disability at 2 years' corrected age.
Scientific title
For extremely low birthweight babies, does higher intravenous protein intake in the first 5 days after birth improve survival free from neurodevelopmental disability at 2 years' corrected age.
Secondary ID [1] 281361 0
NIL
Universal Trial Number (UTN)
U1111-1135-5325
Trial acronym
PROVIDE: The impact of protein IVN on development
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Extremely preterm birth 287583 0
Faltering growth / postnatal growth restriction 287584 0
Neurodevelopmental outcome following preterm birth 287585 0
Condition category
Condition code
Diet and Nutrition 287909 287909 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 287919 287919 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All babies will receive intravenous nutrition according to NICU practices. In addition, babies will be randomised to the intervention or placebo control:

Intervention group: Babies will receive 8.5% intravenous amino acid solution at 0.5 mL/hr via the umbilical arterial catheter (UAC), providing an additional 1 to 2 g/Kg.d protein for 5 days. If the UAC is required for longer than 5 days, the solution will be changed to 0.45% saline.
Intervention code [1] 285822 0
Prevention
Intervention code [2] 285832 0
Treatment: Other
Comparator / control treatment
The UAC solution will be 0.45% saline at 0.5 mL/hr maintained for 5 days.
Control group
Placebo

Outcomes
Primary outcome [1] 288126 0
Survival free from neurodevelopmental disability at 2 years’ corrected age, defined as cerebral palsy, blindness, deafness, developmental delay (defined as a standardised score more than 1 SD below the mean (<-1 SD) on the Bayley Scales of Infant Development Edition 3 [BSID-III] scores), Gross Motor Function Classification System score (Doyle LW: Changing availability of neonatal intensive care for extremely low birthweight infants in Victoria over two decades. Med J Aust 2004, 181(3):136-139).
Timepoint [1] 288126 0
2 years corrected age
Secondary outcome [1] 299460 0
Body composition (the amount and ratio of lean body mass to fat mass) measured by air displacement plethysmography
Timepoint [1] 299460 0
36 weeks corrected gestational age
Secondary outcome [2] 299461 0
Growth velocity calculated using the exponential method. (Patel AL, Engstrom JL, Meier PP, Kimura RE. Accuracy of methods for calculating postnatal growth velocity for extremely low birth weight infants. Pediatrics 2005;116:1466-73)
Timepoint [2] 299461 0
Birth to 36 weeks corrected gestational age.
Secondary outcome [3] 308194 0
Crown heel length, weight and head circumference Z-score change according to Fenton 2013 and WHO growth standards.
Timepoint [3] 308194 0
Birth to 28 days, 8 weeks and 36 weeks corrected gestational age, discharge and 2 years corrected age. Collected prospectively from medical records at 36 weeks corrected age, discharge and 2 years.
Secondary outcome [4] 391613 0
Composite motor function score, defined as the average age-adjusted score for the Nine-hole Peg Board Test and Standing Balance Test
Timepoint [4] 391613 0
At 6-7 years of age.
Secondary outcome [5] 411829 0
The presence of intraventricular haemorrhage (IVH).
Timepoint [5] 411829 0
Collected prospectively from medical records at 36 weeks corrected age.
Secondary outcome [6] 411830 0
Intravenous nutritional intake until 28 days (fluid, energy, protein, fat, carbohydrate, vitamins and minerals).
Timepoint [6] 411830 0
Collected prospectively from medical records at 28 days
Secondary outcome [7] 411831 0
Individual components of the primary outcome - cerebral palsy. Assessed at the 2 years corrected age follow-up visit by a paediatrician as part of the trial.
Timepoint [7] 411831 0
Assessed at the follow-up visit at 2 years corrected age.
Secondary outcome [8] 411832 0
The presence of chronic lung disease (need for oxygen at 36 weeks’ post-menstrual age) collected prospectively from medical records at 36 weeks corrected age.
Timepoint [8] 411832 0
Collected prospectively from medical records at 36 weeks corrected age.
Secondary outcome [9] 411833 0
Retinopathy of prematurity grades 3 and 4 as per the International Classification of Retinopathy of Prematurity collected prospectively from medical records at 36 weeks corrected age.
Timepoint [9] 411833 0
Collected prospectively from medical records at 36 weeks corrected age.
Secondary outcome [10] 411834 0
Necrotising enterocolitis (defined as Bell’s stage 2 or higher)
Timepoint [10] 411834 0
Collected prospectively from medical records at 36 weeks corrected age.
Secondary outcome [11] 411835 0
Patent ductus arteriosus diagnosed by echocardiography needing treatment,
Timepoint [11] 411835 0
Collected prospectively from medical records at 36 weeks corrected age.
Secondary outcome [12] 411836 0
Early (less than or equal to 48 hours after birth) and late-onset sepsis (beyond 48 hours after birth) culture-proven [positive bacterial culture in cerebrospinal fluid, blood or urine with clinical signs of infection and requiring antibiotic therapy for greater than or equal to 5 days or for a shorter period if the participant died] and probable [absent positive culture but with clinical signs of infection and a plan for greater than or equal to 5 days of antibiotics].
Timepoint [12] 411836 0
Collected prospectively from medical records at 36 weeks corrected age.
Secondary outcome [13] 411837 0
Enteral nutritional intake until 28 days (fluid, energy, protein, fat, carbohydrate, vitamins and minerals).
Timepoint [13] 411837 0
Collected prospectively from medical records at 28 days.
Secondary outcome [14] 411838 0
Total nutritional intake until 28 days (fluid, energy, protein, fat, carbohydrate, vitamins and minerals).
Timepoint [14] 411838 0
Collected prospectively from medical records at 28 days.
Secondary outcome [15] 411839 0
Feed type and nutritional supplementation at NICU discharge.
Timepoint [15] 411839 0
Collected prospectively from medical records at discharge.
Secondary outcome [16] 411840 0
Length of stay
Timepoint [16] 411840 0
Collected prospectively from medical records at at discharge
Secondary outcome [17] 411841 0
Individual components of the primary outcome - blindness
Timepoint [17] 411841 0
Assessed at 2 years corrected age
Secondary outcome [18] 411842 0
Individual component of the primary outcome - developmental delay (defined as a standardised score more than 1 SD below the mean (<-1 SD) on the Bayley Scales of Infant Development Edition 3 scores)
Timepoint [18] 411842 0
Assessed at 2 years corrected age
Secondary outcome [19] 411843 0
Individual component of the primary outcome - Gross Motor Function Classification System score
Timepoint [19] 411843 0
Assessed at 2 years corrected age
Secondary outcome [20] 411844 0
The presence of cerebellar haemorrhage


Timepoint [20] 411844 0
Collected prospectively from medical records at 36 weeks corrected age.
Secondary outcome [21] 411845 0
The presence of peri-ventricular leukomalacia.
Timepoint [21] 411845 0
Collected prospectively from medical records at 36 weeks corrected age.

Eligibility
Key inclusion criteria
Babies <1,000 g at birth and admitted to NICU with a UAC placed.
Minimum age
No limit
Maximum age
24 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Birth weight greater than or equal to 1000 g; admission to NICU >24 hours after birth; multiple birth >2 children; congenital disorder affecting growth; inborn error of metabolism; in danger of imminent death.

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)
Within 24 hours of birth babies will be randomly allocated to treatment and control groups by central randomisation.

Allocation to intervention or control will be concealed. Allocation to the study will not be concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation Via a web-based interface managed by an independent database controller (IDC). Randomisation will be stratified for recruitment centre, sex and for appropriate-for-gestational-age / small-for-gestational-age status.
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
nil
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
23/04/2014
Actual
29/04/2014
Date of last participant enrolment
Anticipated
30/09/2018
Actual
31/10/2018
Date of last data collection
Anticipated
30/06/2021
Actual
31/05/2021
Sample size
Target
430
Accrual to date
Final
434
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11448 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 23464 0
3052 - Parkville
Recruitment outside Australia
Country [1] 4587 0
New Zealand
State/province [1] 4587 0

Funding & Sponsors
Funding source category [1] 289213 0
Charities/Societies/Foundations
Name [1] 289213 0
Nurture Foundation
Country [1] 289213 0
New Zealand
Funding source category [2] 289214 0
Other
Name [2] 289214 0
Gravida
Country [2] 289214 0
New Zealand
Funding source category [3] 289215 0
Charities/Societies/Foundations
Name [3] 289215 0
Cure Kids
Country [3] 289215 0
New Zealand
Funding source category [4] 289216 0
Government body
Name [4] 289216 0
Lotteries Health Research
Country [4] 289216 0
New Zealand
Funding source category [5] 289320 0
Charities/Societies/Foundations
Name [5] 289320 0
A+ Trust
Country [5] 289320 0
New Zealand
Funding source category [6] 300159 0
Government body
Name [6] 300159 0
Health Research Council of New Zealand
Country [6] 300159 0
New Zealand
Primary sponsor type
Individual
Name
Professor Frank Bloomfield
Address
Liggins Institute / Department of Paediatrics
University of Auckland
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 284929 0
Individual
Name [1] 284929 0
Professor Caroline Crowther
Address [1] 284929 0
Liggins Institute
University of Auckland
Private Bag 92019
Auckland 1142
Country [1] 284929 0
New Zealand
Other collaborator category [1] 277116 0
Individual
Name [1] 277116 0
Dr Cathryn Conlon
Address [1] 277116 0
Massey University
Institute of Food, Nutrition and Human Health
Private Bag 102 904
North Shore City
Auckland 0745
Country [1] 277116 0
New Zealand
Other collaborator category [2] 277942 0
Individual
Name [2] 277942 0
Professor Jane Harding
Address [2] 277942 0
Liggins Institute / Department of Paediatrics
University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country [2] 277942 0
New Zealand
Other collaborator category [3] 277943 0
Individual
Name [3] 277943 0
Yannan Jiang
Address [3] 277943 0
Liggins Institute University of Auckland Private Bag 92019 Auckland 1142
Country [3] 277943 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288171 0
Multiregion Ethics committee
Ethics committee address [1] 288171 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 288171 0
New Zealand
Date submitted for ethics approval [1] 288171 0
14/06/2013
Approval date [1] 288171 0
11/07/2013
Ethics approval number [1] 288171 0
No 13/NTB/84

Summary
Brief summary
Postnatal growth restriction, or faltering growth, is almost universal in extremely low birthweight (ELBW) babies. This is largely due to inadequate nutrition, as it is very difficult to maintain nutritional intake in the smallest babies, particularly in the first week after birth. ELBW babies are also at risk of adverse neurodevelopmental outcomes, likely also due, in part, to inadequate nutrition. We have shown that increasing protein intakes in early life prevents faltering growth. We now propose to determine whether increased protein intake in early life in ELBW babies improves neurodevelopmental outcomes through a multicentre, double-blind randomised placebo-controlled trial. The findings of this trial will be of relevance to the management of all preterm babies because the intervention is simple and cheap.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34802 0
Prof Frank Bloomfield
Address 34802 0
Liggins Institute / Department of Paediatrics
University of Auckland
Private Bag 92019
Auckland 1142
Country 34802 0
New Zealand
Phone 34802 0
+64 21 497 598
Fax 34802 0
Email 34802 0
[email protected]
Contact person for public queries
Name 18049 0
Dr Barbara Cormack
Address 18049 0
Neonatal/Paediatric Dietitian
Nutrition Services
Office 2, Level 8. Room 81.038 Support Building, Auckland City Hospital, Private Bag 920 24, Auckland 1142, New Zealand
Country 18049 0
New Zealand
Phone 18049 0
Tel +64 9 307 4949 Ext 23351
Fax 18049 0
Email 18049 0
[email protected]
Contact person for scientific queries
Name 8977 0
Dr Barbara Cormack
Address 8977 0
Neonatal/Paediatric Dietitian
Nutrition Services
Office 2, Level 8. Room 81.038 Support Building, Auckland City Hospital, Private Bag 920 24, Auckland 1142, New Zealand
Country 8977 0
New Zealand
Phone 8977 0
Tel +64 9 307 4949 Ext 23351
Fax 8977 0
Email 8977 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?
All of the IPD collected during the trial will be available upon request after signed collaborative agreement with whoever is leading the IPD metaanalysis.
When will data be available (start and end dates)?
Data available - After the end of the study in 2020 until 'No end date determined'
Available to whom?
After signed collaborative agreement with whoever is leading the IPD metaanalysis.
Available for what types of analyses?
Yes data available for IPD upon request
How or where can data be obtained?
After signed collaborative agreement with whoever is leading the IPD metaanalysis.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2500Study protocolBloomfield FH, Crowther CA, Harding JE, Conlon CA, Jiang Y, Cormack BE. The ProVIDe study: the impact of protein intravenous nutrition on development in extremely low birthweight babies. BMC Pediatr. 2015;15(1):100.  
2501Statistical analysis plan  [email protected]
2502Informed consent form  [email protected]
2503Ethical approval  [email protected]



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePlasma ammonia concentrations in extremely low birthweight infants in the first week after birth: secondary analysis from the ProVIDe randomized clinical trial.2020https://dx.doi.org/10.1038/s41390-019-0730-z
EmbaseRelationships between neonatal nutrition and growth to 36 weeks' corrected age in ELBW babies-secondary cohort analysis from the provide trial.2020https://dx.doi.org/10.3390/nu12030760
EmbaseNeonatal Refeeding Syndrome and Clinical Outcome in Extremely Low-Birth-Weight Babies: Secondary Cohort Analysis From the ProVIDe Trial.2021https://dx.doi.org/10.1002/jpen.1934
EmbaseEarly Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years.2022https://dx.doi.org/10.1056/NEJMoa2204886
Dimensions AIThe ProVIDe study: the impact of protein intravenous nutrition on development in extremely low birthweight babies2015https://doi.org/10.1186/s12887-015-0411-y
N.B. These documents automatically identified may not have been verified by the study sponsor.