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Trial registered on ANZCTR


Registration number
ACTRN12616000925448
Ethics application status
Approved
Date submitted
18/03/2016
Date registered
12/07/2016
Date last updated
15/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of extra intravenous (IV) nutrition compared to standard IV nutrition on growth in moderately preterm babies
Scientific title
A randomised controlled trial comparing the effect on growth of peripheral parenteral nutrition versus 10% glucose during the transition to enteral feeds in moderately preterm infants. The P-PN Study
Secondary ID [1] 288798 0
None
Universal Trial Number (UTN)
U1111-1180-9563
Trial acronym
The P-PN Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Extra-uterine growth failure 298065 0
Preterm birth 298322 0
Condition category
Condition code
Diet and Nutrition 298228 298228 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 298444 298444 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Peripherally administered intravenous peripheral parenteral nutrition (amino acid, glucose 8% and lipids).
The P-PN Study solution will be prepared by Baxter and consist of Primene 30g/L, glucose 80g/L and Heparin 500IU/L. It will be administered at maxmimum rate of 100mL/kg/d, which will give a maximum protein dose of 3 g/kg/d.
The lipid solution is a 17% fat emulsion with added vitamins for injection (SMOFlipid 20% 15ml, Vitalipid N Infant 4ml and Soluvit N 1ml per 20ml. (Fresenius Kabi) It will be manufactured on site at WCH Sterile Manufacturing Pharmacy. It will be administered at a dose of lipid of 2 g/kg/d.
The study and standard solutions will be administered as continuous IV infusions.
When consent, and randomisation has been confirmed, the study fluids will be commenced or the standard fluid will be continued. The lipid infusion will cease when feeds are 100mL/kg/d, and the P-PN Study fluid will cease when the feeds are 100mL/kg/d.
Registered nurses or Registered Midwifes from the Neonatal Unit will administer the study fluids.
The study will occur in the Neonatal intensive care unit (NICU) or special care baby unit (SCBU) at the Women's and Children's Hospital, Adelaide.
The study IV solutions will commence at a total of 45-60mLkg/d and increase 10-15mL/kg/d until full enteral feeds are established. At the clinician's discretion the study fluids will be titrated if there is feed intolerance, or evidence of fluid/nutrition/electrolyte disturbance - for example - fluid overload, increased fluid need, lipid intolerance, hypoglycaemia, or hyperglycaemia.
Protocol adherence checked daily by research nurse
Intervention code [1] 294248 0
Treatment: Other
Comparator / control treatment
The control treatment will be the standard intravenous fluid as per current practice - Glucose 10% (glucose 100 grams per litre) (Baxter Healthcare).
As per standard practice, during days 2-4 of life the following standard bag of fluid will be commenced: Glucose 10%, potassium chloride 20mmol /L, Sodium chloride 0.225% (Glucose 100g /L, Potassium chloride 1.5g/L, Sodium chloride 2.25g/L) (Baxter Healthcare).
The dose of the control fluids will as per standard practice, ie commencing at 45-60 mL/kg/day, and increasing each subsequent by approximately 10-15 mL/kg/day until a maximum of 100 mL/kg/day is achieved or full enteral feeds have been achieved.
The control fluid will be continued until enteral milk feeds are at least 120mL/kg/d.
Control group
Active

Outcomes
Primary outcome [1] 297729 0
The primary outcome of the study is rate of weight gain (grams per day) from birth until 21 days of age. Infants will be weighed daily by clinical staff.
The scales are calibrated annually using standard weights.
Timepoint [1] 297729 0
Weight will be measured daily from birth until 21 days of age.
Secondary outcome [1] 322037 0
Weight gain until discharge.
Timepoint [1] 322037 0
Infants will be weighed daily up to 21 days of age then according to current clinical practice (daily to twice weekly). Infants will also be weighed on day of discharge home.
Secondary outcome [2] 322721 0
Length gain (cm/week) to 21 days of age and discharge home. Research nurses or clinical staff will measure length weekly and on day of discharge home. Duplicate measurements will be taken. Length will be determined in the supine position to the nearest 0.1 cm using a recumbent length board. A third measurement will be taken if there is a discrepancy of more than 5 mm.
Timepoint [2] 322721 0
Length will be measured on day of birth, then weekly until discharge home.
Secondary outcome [3] 322722 0
Head circumference gain (cm/week) to 21 days of age and discharge home. Research nurses or clinical staff will measure head circumference weekly and on day of discharge home. Head circumference will be measured in duplicate around the largest occipito-frontal circumference using a non-stretching tape. A third measurement will be taken if there is a discrepancy of more than 5 mm.
Timepoint [3] 322722 0
Head circumference will measured weekly until discharge home.
Secondary outcome [4] 322723 0
Body composition: Lean body mass will be obtained by weekly Bioelectrical Impedance measurements.
Timepoint [4] 322723 0
BIS will be measured in the first 48 hours of life then weekly until day 21.
Secondary outcome [5] 322724 0
Feed tolerance: The number of days on which one or more feeds have been stopped.
Enteral intake data will be collected prospectively from clinical fluid balance charts.
Timepoint [5] 322724 0
Cessation or witholding feeds will be monitored daily until 21 days of age.
Secondary outcome [6] 322725 0
Protein intake: Parenteral and enteral intake data will be collected prospectively from clinical fluid balance charts. This will include volume, protein and caloric density of intravenous fluids, human milk, formula and fortifier/supplements.
Timepoint [6] 322725 0
Protein intake will be monitored daily until discharge.
Secondary outcome [7] 322726 0
Number of peripheral venous cannulae.
Intravenous cannulae (IVC) data will be collected prospectively from IVC charts.
Timepoint [7] 322726 0
Number of peripheral venous cannulae will be monitored daily until discharge home.
Secondary outcome [8] 322915 0
Feed tolerance: Date first reached an enteral intake of >120 mLs/kg/day and maintained >120 mLs/kg/day for three days.
Parenteral and enteral intake data will be collected prospectively from clinical fluid balance charts.
Timepoint [8] 322915 0
Achievement of full enteral feeds will be monitored daily until discharge.
Secondary outcome [9] 322916 0
Energy intake: Parenteral and enteral intake data will be collected prospectively from clinical fluid balance charts. This will include volume, protein and caloric density of intravenous fluids, human milk, formula and fortifier/supplements.
Timepoint [9] 322916 0
Energy intake will be monitored daily until discharge.
Secondary outcome [10] 322917 0
Duration of peripheral venous cannulae.
Intravenous cannulae (IVC) data will be collected prospectively from IVC charts.
Timepoint [10] 322917 0
Duration of peripheral venous cannulae being in-situ will be monitored daily until discharge.
Secondary outcome [11] 322918 0
Frequency of infiltration/extravasation injuries due to peripheral venous cannulae.
Intravenous cannulae (IVC) data will be collected prospectively from IVC charts.
Timepoint [11] 322918 0
The possibility of infiltration/extravasation injuries due to peripheral venous cannulae will be monitored for daily until discharge.
Secondary outcome [12] 322919 0
Frequency and severity of thrombophlebitis due to peripheral venous cannulae.
Intravenous cannulae (IVC) data will be collected prospectively from IVC charts.
Timepoint [12] 322919 0
The possibility of thrombophlebitis due to peripheral venous cannulae will be monitored for daily until discharge.
Secondary outcome [13] 322920 0
Frequency and severity of line associated sepsis.
Intravenous cannulae (IVC) data will be collected prospectively from IVC charts and medical records.
Timepoint [13] 322920 0
The possibility of line associated sepsis due to peripheral venous cannule will be monitored for daily until discharge.
Secondary outcome [14] 322921 0
Blood urea will be measured.
Timepoint [14] 322921 0
Blood tests will be done on randomisation, days 2, 4, 7 and then weekly until 21 days or discharge home.
Secondary outcome [15] 322922 0
Blood albumin will be measured.
Timepoint [15] 322922 0
Blood tests will be done on randomisation, days 2, 4, 7 and then weekly until 21 days or discharge home.
Secondary outcome [16] 322923 0
Blood triglycerides will be measured.
Timepoint [16] 322923 0
Blood tests will be done on randomisation, days 2, 4, 7 and then weekly until 21 days or discharge home.
Secondary outcome [17] 322924 0
Blood pH will be measured.
Timepoint [17] 322924 0
Blood tests will be done on randomisation, days 2, 4, 7 and then weekly until 21 days or discharge home.
Secondary outcome [18] 322925 0
Blood bicarbonate will be measured.
Timepoint [18] 322925 0
Blood tests will be done on randomisation, days 2, 4, 7 and then weekly until 21 days or discharge home.
Secondary outcome [19] 322926 0
Blood base excess will be measured.
Timepoint [19] 322926 0
Blood tests will be done on randomisation, days 2, 4, 7 and then weekly until 21 days or discharge home.
Secondary outcome [20] 322927 0
Blood sodium will be measured.
Timepoint [20] 322927 0
Blood tests will be done on randomisation, days 2, 4, 7 and then weekly until 21 days or discharge home.
Secondary outcome [21] 322928 0
Blood potassium will measured.
Timepoint [21] 322928 0
Blood tests will be done on randomisation, days 2, 4, 7 and then weekly until 21 days or discharge home.
Secondary outcome [22] 322929 0
Blood spot analyses will be undertaken to determine amino acid (complete metabolic profile).
Timepoint [22] 322929 0
A 30 microL spot of blood will be taken at randomisation then on study days 2, 4, 7, 14 and 21.
Secondary outcome [23] 322930 0
Blood spot analyses will be undertaken to determine polyunsaturated fatty acid (PUFA - most fatty acids including AA, EPA and DHA) profiles.
Timepoint [23] 322930 0
A 30 microL spot of blood will be taken at randomisation then on study days 2, 4, 7, 14 and 21.
Secondary outcome [24] 322931 0
Number of infants requiring central venous catheter insertion.
Central venous catheter data will be collected prospectively from the medical records.
Timepoint [24] 322931 0
Monitored daily until discharge home.
Secondary outcome [25] 322932 0
Grade of intra-ventricular haemorrhage (IVH).
IVH data will be collected prospectively from the medical records.
Timepoint [25] 322932 0
Monitored daily until discharge home.
Secondary outcome [26] 322933 0
Confirmed sepsis.
Sepsis data will be collected prospectively from the medical records.
Timepoint [26] 322933 0
Monitored daily until discharge home.
Secondary outcome [27] 322934 0
Confirmed necrotising enterocolitis (NEC).
NEC data will be collected prospectively from the medical records.
Timepoint [27] 322934 0
Monitored daily until discharge home.
Secondary outcome [28] 322935 0
Grade of retinopathy of prematurity (ROP).
ROP data will be collected prospectively from the medical records.
Timepoint [28] 322935 0
Monitored daily until discharge home.
Secondary outcome [29] 322936 0
Total dose of corticosteroid use.
Steroid use will be collected prospectively from the medical records.
Timepoint [29] 322936 0
Monitored daily until discharge home.
Secondary outcome [30] 322937 0
Days of oxygen therapy.
Oxygen therapy data will be collected prospectively from the medical records.
Timepoint [30] 322937 0
Monitored daily until discharge home.
Secondary outcome [31] 322938 0
Oxygen at 36 weeks post menstrual age.
Oxygen use data will be collected prospectively from the medical records.
Timepoint [31] 322938 0
Monitored daily until 36 weeks post menstrual age.
Secondary outcome [32] 322939 0
Length of hospital stay.
Timepoint [32] 322939 0
Assessed at discharge.
Secondary outcome [33] 323742 0
Hypoglycaemic events. Less than 2.5mmol/L.
Blood glucose data will be collected prospectively from the medical records.
Timepoint [33] 323742 0
Monitored daily until discharge home.

Eligibility
Key inclusion criteria
1. Delivered in the Women’s and Children’s Hospital
2. Born 30+0 to 33+6 weeks of gestation from singleton or multiple births
3. Less than 24 hours of age
4. Requires intravenous fluids
5. Has parent or guardian capable of giving informed consent
Minimum age
0 Hours
Maximum age
24 Hours
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Receiving central venous fluids
2. Major congenital or chromosomal 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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted blocks of random sizes. The block sizes will not be disclosed to ensure concealment.
Stratification will occur for sex and gestation (30+0 to 31+6 weeks gestation, and 32+0 to 33+6 weeks gestation). Infants from multiple births will be randomised individually.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Assuming a standard deviation in weight gain of 5 grams per day in this population, 45 infants per group (total of 90 infants) will be required to detect a difference in weight gain of 3 grams per day between groups with 80% power, (P <0.05). Neonatologists have indicated that this is a clinically important difference on which they would base practice change.
The primary outcome of weight gain will be analysed using a linear mixed effects model, with clustering due to repeated measures and multiple births accounted for in the model. Analyses will be performed on data from all babies randomised on an intention-to-treat basis and a two-tailed probability <0.05 will be considered statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 5470 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [2] 6645 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 12953 0
5006 - North Adelaide
Recruitment postcode(s) [2] 14269 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 293163 0
Charities/Societies/Foundations
Name [1] 293163 0
Women's and Children's Hospital Foundation
Address [1] 293163 0
Ground Floor 55 King William Road North Adelaide, 5006, SA
Country [1] 293163 0
Australia
Primary sponsor type
Government body
Name
Women's and Children's Health Network
Address
Level 2 Samuel Way Building
72 King William Rd
North Adelaide, 5006, SA
Country
Australia
Secondary sponsor category [1] 291958 0
None
Name [1] 291958 0
None
Address [1] 291958 0
None
Country [1] 291958 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294656 0
Women's and Children's Health Network
Ethics committee address [1] 294656 0
Research Secretariat
Level 2 Samuel Way Building
72 King William Rd
North Adelaide, 5006, SA
Ethics committee country [1] 294656 0
Australia
Date submitted for ethics approval [1] 294656 0
10/09/2015
Approval date [1] 294656 0
11/05/2016
Ethics approval number [1] 294656 0
HREC/15/WCHN/134

Summary
Brief summary
Many babies are born early for a variety of reasons. These premature babies have more problems with growth and later development than other babies born at term.
Babies born between 6 and 10 weeks early miss out on the important nutrition from the placenta. In addition, these newborn babies often lose further weight in the first week of life. Despite these recognised problems there is very little research about how best to address these issues.
At present, these babies receive a simple sugar and water solution through an IV line whilst building up oral feeds with either breast milk or artificial formula. As a result many babies lose weight but also protein and fat as the simple sugar and water solution is unable to provide these babies with the more complex mixture of dietary supplementation they require.
It is the purpose of this study to provide premature babies born between 6 and 10 weeks early with a more complex dietary infusion delivered through an IV line to improve their nutrition and reduce weight loss after premature birth.
Ninety babies will be enrolled in the study with each having an equal chance of receiving either the routine sugar and water IV solution or a combined solution of sugar, protein, fat and water also through an IV line. The baby’s growth will be monitored up to three weeks of age.
This study will provide important information about how best to improve the nutrition in premature babies, which we hope will also improve their longer term outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62502 0
Dr Dennis Bonney
Address 62502 0
Department of Neonatal Medicine
Women's and Children's Hospital
72 King William Rd
North Adelaide, 5006, SA
Country 62502 0
Australia
Phone 62502 0
+61 8 81617631
Fax 62502 0
Email 62502 0
dennis.bonney@sa.gov.au
Contact person for public queries
Name 62503 0
Dr Dennis Bonney
Address 62503 0
Department of Neonatal Medicine
Women's and Children's Hospital
72 King William Rd
North Adelaide, 5006, SA
Country 62503 0
Australia
Phone 62503 0
+61 8 81617631
Fax 62503 0
Email 62503 0
dennis.bonney@sa.gov.au
Contact person for scientific queries
Name 62504 0
Dr Dennis Bonney
Address 62504 0
Department of Neonatal Medicine
Women's and Children's Hospital
72 King William Rd
North Adelaide, 5006, SA
Country 62504 0
Australia
Phone 62504 0
+61 8 81617631
Fax 62504 0
Email 62504 0
dennis.bonney@sa.gov.au

No information has been provided regarding IPD availability
Summary results
No Results