The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616000160437
Ethics application status
Approved
Date submitted
5/02/2016
Date registered
10/02/2016
Date last updated
12/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of feeding on blood flow to the gut in preterm infants receiving red blood cell transfusion
Scientific title
The effects of enteral feeding during red blood cell transfusion on the cerebro-splanchnic oxygenation ratio (CSOR) in preterm infants with anaemia, as measured by near infrared spectroscopy (NIRS)
Secondary ID [1] 288487 0
None
Universal Trial Number (UTN)
U1111-1179-2618
Trial acronym
FEEding DURing Red Cell Transfusion (FEEDUR RCT)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transfusion associated necrotising enterocolitis 297542 0
Preterm birth 297562 0
Anaemia 297563 0
Condition category
Condition code
Oral and Gastrointestinal 297743 297743 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Reproductive Health and Childbirth 297762 297762 0 0
Complications of newborn
Blood 297763 297763 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1) Withholding of enteral feeds during red cell transfusion for 12 hours from the start of the transfusion.
2) Restriction of enteral feed volume to 120 ml/kg/day, maximum calorie concentration 20 kcal/30ml.
Intervention code [1] 293846 0
Treatment: Other
Comparator / control treatment
Continuing of enteral feeds during red cell transfusion for 24 hours from the start of the transfusion. Enteral feeds will be continued according to the feeding regime prior to the transfusion, which may be continuous feeds or bolus feeds every 1-3 hours.
Control group
Active

Outcomes
Primary outcome [1] 297272 0
Mean CSOR, using near-infrared spectroscopy (NIRS)
Timepoint [1] 297272 0
1 hour prior to transfusion, during transfusion, immediately post-transfusion, 12 & 24 hours after transfusion
Primary outcome [2] 297273 0
Mean mesenteric fractional oxygen extraction, using near-infrared spectroscopy (NIRS)
Timepoint [2] 297273 0
1 hour prior to transfusion, during transfusion, immediately post-transfusion, 12 & 24 hours after transfusion
Secondary outcome [1] 320545 0
Time to return to full feeds, defined as the number of hours after the 24 hour study period until the infant is receiving the same feed volume as prior to the transfusion.
Timepoint [1] 320545 0
Post-transfusion
Secondary outcome [2] 320546 0
Feed intolerance, defined as gastric aspirates >30% of feed volume or vomiting
Timepoint [2] 320546 0
24 hours after completion of study
Secondary outcome [3] 320547 0
Abdominal distension, assessed by review of medical and nursing documentation.
Timepoint [3] 320547 0
24 hours after completion of study
Secondary outcome [4] 320548 0
Adverse events including transfusion reactions, suspected or proven sepsis, necrotising enterocolitis, assessed by review of medical records
Timepoint [4] 320548 0
24 hours after completion of study
Secondary outcome [5] 320549 0
Necrotising enterocolitis, assessed by data linkage to patient medical records
Timepoint [5] 320549 0
At time of discharge
Secondary outcome [6] 320550 0
Late onset sepsis, assessed by data linkage to patient medical records
Timepoint [6] 320550 0
At time of discharge
Secondary outcome [7] 320638 0
Mortality, assessed by data linkage to patient medical records
Timepoint [7] 320638 0
At time of disharge

Eligibility
Key inclusion criteria
Preterm infants <35 weeks gestation
Receiving red cell transfusion for anaemia
Enteral feeding of at least 120 ml/kg/day
Minimum age
No limit
Maximum age
4 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
<28 weeks corrected gestation at time of intervention
Growth restriction (BW < 3rd centile)
Major congenital anomalies (including severe cardiac or cerebral disease, any malformation or disease of the gastrointestinal tract)
Diagnosis of necrotising enterocolitis, spontaneous intestinal perforation or history of abdominal surgery
Need for vasopressor therapy
Cutaneous disease not allowing for placement of NIRS sensor

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Based on recently published reference values in preterm neonates, we would expect mean regional cerebral oxygen saturations to be approximately 70% with a standard deviation of approximately 7%. To detect a 10% change in mean cerebral oxygenation, a sample size of at least 16 neonates will be required to achieve 80% power at 0.05 level. We plan to recruit 20 infants per group.
Assuming normal distribution of data, we will use parametric statistics to analyse our data. We will use paired t-tests to determine any difference in pre-transfusion mean CSOR and post-transfusion CSOR in the two groups of infants. Independent t-tests will be used to evaluate differences in mean CSOR between groups at all time points. Repeated measures ANOVA will be used to analyse changes in CSOR over the four pre-specified time points. Post-hoc tests, such as Tukey's, will be performed to further analyse significant results. Clinical outcome data will be analysed using a combination of chi-squared, ANOVA and Kruskall-Wallis tests as appropriate.

Recruitment
Recruitment status
Completed
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)
NSW
Recruitment hospital [1] 5234 0
Royal Hospital for Women - Randwick
Recruitment postcode(s) [1] 12705 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 292836 0
Charities/Societies/Foundations
Name [1] 292836 0
Madison Capaldi Research Fund
Address [1] 292836 0
C/O Royal Hospital for Women Foundation
Royal Hospital for Women
Barker St
Randwick NSW 2031
Country [1] 292836 0
Australia
Primary sponsor type
Individual
Name
Tim Schindler
Address
Newborn Care Centre
Royal Hospital for Women
Barker St
Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 291595 0
None
Name [1] 291595 0
Address [1] 291595 0
Country [1] 291595 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294341 0
South Eastern Sydney Local Health District - Northern Sector Human Research Ethics Committee
Ethics committee address [1] 294341 0
Research Support Office
G71, East Wing
Edmund Blacket Building
Prince of Wales Hospital
Randwick NSW 2031
Ethics committee country [1] 294341 0
Australia
Date submitted for ethics approval [1] 294341 0
31/10/2014
Approval date [1] 294341 0
29/05/2015
Ethics approval number [1] 294341 0
HREC/14/POWH/624

Summary
Brief summary
Background:
Development of anaemia in preterm infants is a common occurrence during hospitalisation as a result of iatrogenic blood loss and poor erythropoiesis. A significant proportion of extremely preterm infants are exposed to one or more RBC transfusions during their neonatal intensive care unit (NICU) stay. The association between red blood cell (RBC) transfusions and the development of necrotizing enterocolitis (NEC) in preterm infants was first recognized in the late 1980’s and has since been increasingly recognized. This association between RBC transfusion and NEC may coincide as a result of the timing of their occurrence, as most preterm infants will receive transfusions within the first 4 weeks of life, which is the same time frame for the development of NEC.
Mechanisms related to the development of TANEC are unknown. Several hypotheses have been proposed including the prolonged storage of blood, increased viscosity of blood, perfusion-reperfusion injury and enteral feeding. The effect of enteral feeding during RBC transfusion on the mesenteric perfusion and oxygenation has not been fully elucidated. Due to the association between NEC and feeding practices in the preterm infants, there have been concerns about the effects of feeding during RBC transfusion. As a result, there is a wide variety of feeding practices during RBC transfusion of preterm infants including withholding of feeds to reduce the risk of NEC.
Technological advances in near-infrared spectroscopy (NIRS) have allowed for the measurement of oxygenated and deoxygenated haemoglobin within tissue in real time. NIRS is able to measure changes in signals received via the skin sensors and calculate the proportion of haemoglobin in oxygenated and deoxygenated states from a mixed capillary, venous and arterial sample in the tissues approximately 2cm below the sensor placement. This allows for the non-invasive real-time measurement of the balance between oxygen supply and tissue demand. This technology has allowed for the continuous measurement of tissue oxygenation of the cerebral and splanchnic beds and for demonstration of differential tissue perfusion during periods of haemodynamic instability, anaemia and RBC transfusions. Autoregulation of brain perfusion allows for the oxygenation of the brain to be preserved except in the most severe situations. Thus, a ratio of cerebral splanchnic oxygenation has been proposed to be able to measure changes in gut perfusion.
Aim:
To assess the effect of feeding and withholding of feeding on gut oxygenation and perfusion in preterm infants receiving RBC transfusions.
Hypothesis:
We hypothesize that mean CSOR and mean mesenteric FOE during RBC transfusion will not be different between preterm infants in the withheld group and the full volume group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63334 0
Dr Tim Schindler
Address 63334 0
Newborn Care Centre
Royal Hospital for Women
Barker St
Randwick NSW 2031
Country 63334 0
Australia
Phone 63334 0
+61293826190
Fax 63334 0
+61293826191
Email 63334 0
tim.schindler@health.nsw.gov.au
Contact person for public queries
Name 63335 0
Dr Tim Schindler
Address 63335 0
Newborn Care Centre
Royal Hospital for Women
Barker St
Randwick NSW 2031
Country 63335 0
Australia
Phone 63335 0
+61293826190
Fax 63335 0
+61293826191
Email 63335 0
tim.schindler@health.nsw.gov.au
Contact person for scientific queries
Name 63336 0
Dr Tim Schindler
Address 63336 0
Newborn Care Centre
Royal Hospital for Women
Barker St
Randwick NSW 2031
Country 63336 0
Australia
Phone 63336 0
+61293826190
Fax 63336 0
+61293826191
Email 63336 0
tim.schindler@health.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary