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Trial registered on ANZCTR


Registration number
ACTRN12619001773123
Ethics application status
Approved
Date submitted
7/09/2019
Date registered
13/12/2019
Date last updated
13/12/2019
Date data sharing statement initially provided
13/12/2019
Date results information initially provided
13/12/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Energy-Enhanced Parenteral Nutrition in preterm newborns
Scientific title
Long term effects of Energy-Enhanced Parenteral Nutrition in preterm newborns
Secondary ID [1] 299210 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
preterm newborns 314325 0
Parenteral Nutrition 314328 0
Condition category
Condition code
Diet and Nutrition 312676 312676 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 313897 313897 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous administration of parenteral nutrition given by neonatal specialist, starting from the first day of life. Adherence to the intervention was monitored by clinical observation. For newborns with a birth weight less than 1000 g in the Cohort B: Energy starting dose 45 kcal/kg/day and target dose 105 kcal/kg/day at 7 days of life; Proteins starting dose 2.0 g/kg/day and target dose 4.0 g/kg/day at 7 days of life; Dextrose starting dose 7.0 g/kg/day and target dose 14.0 at 7 days of life; Lipids starting dose 1.0 g/kg/day and target dose 3.5 at 7 days of life. For newborns with a birth weight greater than or equal to 1000 g in the Cohort B: Energy starting dose 45 kcal/kg/day and target dose 100 kcal/kg/day at 7 days of life; Proteins starting dose 2.0 g/kg/day and target dose 3.5 g/kg/day at 7 days of life; Dextrose starting dose 7.0 g/kg/day and target dose 14.5 at 7 days of life; Lipids starting dose 1.0 g/kg/day and target dose 3.0 at 7 days of life.
Intervention code [1] 315511 0
Treatment: Other
Comparator / control treatment
Intravenous administration of parenteral nutrition given by neonatal specialist, starting from the first day of life. Adherence to the intervention was monitored by clinical observation. Data of Cohort A was collected from Policlinico Umberto I records from 1st January 2015 to 31 January 2016. For newborns with a birth weight less than 1000 g in the Cohort A: Energy starting dose 55 kcal/kg/day and target dose 120 kcal/kg/day at 7 days of life; Proteins starting dose 2.0 g/kg/day and target dose 4.0 g/kg/day at 7 days of life; Dextrose starting dose 7.0 g/kg/day and target dose 16.0 at 7 days of life; Lipids starting dose 2.0 g/kg/day and target dose 4.0 at 7 days of life. For newborns with a birth weight greater than or equal to 1000 g in the Cohort A: Energy starting dose 60 kcal/kg/day and target dose 110 kcal/kg/day at 7 days of life; Proteins starting dose 2.0 g/kg/day and target dose 3.5 g/kg/day at 7 days of life; Dextrose starting dose 8.5 g/kg/day and target dose 15 at 7 days of life; Lipids starting dose 2.0 g/kg/day and target dose 3.5 at 7 days of life.
Control group
Historical

Outcomes
Primary outcome [1] 321324 0
Body weight measured by digital scale
Timepoint [1] 321324 0
At 24 months of life.
Primary outcome [2] 321726 0
Head circumference measured by tape measurement
Timepoint [2] 321726 0
At 24 months of life.
Primary outcome [3] 321727 0
Length measured from the top of the head to the sole of the feet, using a neonatal stadiometer,
Timepoint [3] 321727 0
At 24 months of life.
Secondary outcome [1] 374679 0
The rate of patients with Extrauterine growth retardation (EUGR), defined as a reduction in percentiles >2.0 SD in body weight (measured by digital scale). between birth and 36 weeks of postmestrual age (PMA), according with INeS charts (http://inescharts.com).
Timepoint [1] 374679 0
At 36 weeks of PMA

Eligibility
Key inclusion criteria
Newborns with gestational age <32 weeks or with birth weight <1500 g,
Minimum age
0 Days
Maximum age
2 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Infants with major congenital malformations, inborn errors of metabolism, congenital infections, hospital discharge or death within 72 hours of life.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This study compared two Cohorts of newborns, consecutively observed during two different periods in NICU of Policlinico Umberto I, receiving different energy intakes through PN in the first weeks of life. Cohort A included newborns observed from the 1st of January 2015 to 31 January 2016 (historical control), and Cohort B included newborns observed from the 1st of February 2016 to 31 March 2017 (intervention). We provided a clinical follow-up to evaluate growth until 24 months of adjusted age for both Cohorts of the study.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis performed using Statistical Package for Social Science software for Microsoft Windows (SPSS Inc, Chicago, IL), version 22.0. Check for normality using Shapiro-Wilk test. The mean and standard deviation or median and interquartile range summarised continuous variables. Cohorts compared using chi-square test for categorical variable and t-test or Mann-Whitney for paired and unpaired variables. Multivariate analysis using binary logistic regression analysis to evaluate whether GA, sex, pH of cord blood at birth or PN protocol, influenced growth at 36 weeks PMA and at 24 months of life. The level of significance for all statistical tests: 2-sides (p<0.05).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/01/2015
Date of last participant enrolment
Anticipated
Actual
31/03/2017
Date of last data collection
Anticipated
Actual
3/06/2019
Sample size
Target
120
Accrual to date
Final
130
Recruitment outside Australia
Country [1] 21844 0
Italy
State/province [1] 21844 0
Rome

Funding & Sponsors
Funding source category [1] 303755 0
University
Name [1] 303755 0
Department of Maternal and Child Health Policlinico Umberto I, University La Sapienza, Rome, Italy
Country [1] 303755 0
Italy
Primary sponsor type
University
Name
Department of Maternal and Child Health Policlinico Umberto I, University La Sapienza, Rome, Italy
Address
Viale del Policlinico, 155 , 00161 Roma RM
Country
Italy
Secondary sponsor category [1] 303873 0
None
Name [1] 303873 0
none
Address [1] 303873 0
Country [1] 303873 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304276 0
Policlinico Umberto I
Ethics committee address [1] 304276 0
Viale del Policlinico, 155, 00161 Roma RM
Ethics committee country [1] 304276 0
Italy
Date submitted for ethics approval [1] 304276 0
01/09/2018
Approval date [1] 304276 0
13/09/2018
Ethics approval number [1] 304276 0
5089

Summary
Brief summary
To assess the best energy intake for very low birth weight newborns, considering both possible benefits for growth and risk of metabolic complications, we designed a prospective study, comparing Cohort of newborns, which received Energy-Enhanced (Cohort A) vs. Standard (Cohort B) Parenteral Nutrition. The main outcome measure was the growth until 24 months of life. Extra-uterine growth retardation, complications associated with PN, survival, length of the hospital stay and morbidity at time point of 36 weeks of Post Menstrual Age were also measured.
Trial website
Trial related presentations / publications
Public notes
Since the 1st of January 2015, we prospectively collected, in a specific database, data regarding metabolic complications, nutritional intakes, morbidity, survival during hospitalization and growth until 24 months of life of all VLBW newborns consecutively observed in the NICU of Policlinico Umberto I. According with our policy, we collected and recorded only data of newborns for which parents gave informed signed consent.
From the 1st of January 2015 to 31 January 2016, we used an aggressive PN protocol. Starting from the 1st of February 2016, we adopted a new PN protocol, consisting in a reduced energy intake.
To verify the effects of the change of nutritional policy on the children growth at 24 months of life, we designed a study protocol that was submitted to Ethical Committee. We obtained ethics approval in 13/09/2018.
Thus, in the first Cohort of the study we included newborns observed in the NICU from the 1st of January 2015 to 31 January 2016, and followed in paediatric office of NICU of Policlinico Umberto I for growth assessment until 31 January 2018 (i.e. historical Cohort).
In the second Cohort of the study, we included newborns admitted in the NICU from the 1st of February 2016 to 31 March 2017. On the 3rd June of 2019 we completed the follow-up of the last infant enrolled in the second Cohort of the study (namely “interventional Cohort”). Finally, we concluded the study and we analysed data prospectively collected in our database.

Contacts
Principal investigator
Name 96366 0
Prof Gianluca Terrin
Address 96366 0
Department of Maternal and Child Health Policlinico Umberto I, University La Sapienza, Rome, Italy, Viale del Policlinico 155, 00161 Roma RM
Country 96366 0
Italy
Phone 96366 0
+39 0649972536
Fax 96366 0
Email 96366 0
[email protected]
Contact person for public queries
Name 96367 0
Prof Gianluca Terrin
Address 96367 0
Department of Maternal and Child Health Policlinico Umberto I, University La Sapienza, Rome, Italy, Viale del Policlinico 155, 00161 Roma RM
Country 96367 0
Italy
Phone 96367 0
+39 0649972536
Fax 96367 0
Email 96367 0
[email protected]
Contact person for scientific queries
Name 96368 0
Prof Gianluca Terrin
Address 96368 0
Department of Maternal and Child Health Policlinico Umberto I, University La Sapienza, Rome, Italy, Viale del Policlinico 155, 00161 Roma RM
Country 96368 0
Italy
Phone 96368 0
+39 0649972536
Fax 96368 0
Email 96368 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


What supporting documents are/will be available?




Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 378327-(Uploaded-07-09-2019-22-07-00)-Basic results summary.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLong-term effects on growth of an energy-enhanced parenteral nutrition in preterm newborn: A quasi-experimental study.2020https://dx.doi.org/10.1371/journal.pone.0235540
N.B. These documents automatically identified may not have been verified by the study sponsor.