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Trial registered on ANZCTR


Registration number
ACTRN12615000940572
Ethics application status
Approved
Date submitted
26/02/2015
Date registered
8/09/2015
Date last updated
20/11/2018
Date data sharing statement initially provided
20/11/2018
Date results information initially provided
20/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of single versus multi-strain probiotic supplementation on the time to full enteral feeds in preterm neonates – a double blind randomised controlled trial
Scientific title
Effect of single versus multi-strain probiotic supplementation on the time to full enteral feeds in preterm neonates – a double blind randomised controlled trial
Secondary ID [1] 286278 0
Nil known
Secondary ID [2] 286583 0
nil
Universal Trial Number (UTN)
Trial acronym
SiMPro Study (Single or Multiple Probiotics for neonates)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
enteral nutrition in preterm neonates 294344 0
gut colonisation
294844 0
faecal short chain fatty acids 294845 0
Condition category
Condition code
Oral and Gastrointestinal 294663 294663 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Diet and Nutrition 294664 294664 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 295113 295113 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: Mixture of 3 strains (B. breve M-16V, B. longum subsp. infantis M-63 and B. longum subsp. longum BB536 (1 billion CFU of each strain per 1 g sachet: 3-strains group)
Frequency of administration: 1 sachet per day when on minimal enteral feed, 2 sachets per day when > 50 ml/kg/day enteral feeds.
Duration of administration: From commencement of enteral feeds till 37 completed weeks of gestation
Mode of administration: reconstituted with breast milk, so oral liquid
Intervention code [1] 291299 0
Treatment: Other
Comparator / control treatment
Control: Single strain product containing B. breve M-16V (3 billion CFU per 1 g sachet)
Control group
Active

Outcomes
Primary outcome [1] 294418 0
Time to full enteral feeds (time to achieve 150 ml/kg/day of enteral milk feeds from the day of randomisation) will be the time point for assessment of primary outcome
Timepoint [1] 294418 0
from commencement of enteral feeds till 37 completed weeks of gestation
Secondary outcome [1] 313268 0
All-cause mortality(clinical notes review within 1 month of mortality)
Timepoint [1] 313268 0
within 3-4 months of discharge from the hospital
Secondary outcome [2] 313269 0
Gut flora and stool colonisation (assayed by conventional stool culture methods)
Timepoint [2] 313269 0
after completion of enrolment, preferably 3-4 months post discharge from hospital
Secondary outcome [3] 314270 0
duration of parenteral nutrition (by review of inbuilt data available in our neonatal database)
Timepoint [3] 314270 0
during patient stay in hospital or post discharge, within 3-4 months of patient discharge
Secondary outcome [4] 314271 0
Necrotizing enterocolitis (NEC)
(assayed by clinical record review)
Timepoint [4] 314271 0
after patient discharge, within 3-4 months following discharge of a patient
Secondary outcome [5] 314272 0
Incidence of Late onset sepsis (assayed by blood tests and clinical examination)
Timepoint [5] 314272 0
after patient discharge, within 3-4 months following pateint discharge
Secondary outcome [6] 316614 0
NEC related mortality (by review of medical records)
Timepoint [6] 316614 0
after patient death, within 1 month upto a maximum of 4 months post discharge

Eligibility
Key inclusion criteria
(1) Gestation <28 weeks at birth (2) ready to commence on milk feeds or on milk feeds for <12 hours (3) Informed parental consent
Minimum age
7 Days
Maximum age
10 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Congenital malformations (2) Chromosomal aberrations (3) Not ready for feeds or on feeds for > 12 hours

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)
All babies < 28 weeks gestation admitted into the neonatal nursery will be eligible for enrolment unless they satisfy the exclusion criteria of the study. Allocation concealment will be optimised by prescribing allocation only after informed parental consent and recording the basic neonatal data.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Group assignment will be allocated by a computer generated randomisation sequence. Opaque, sealed, coded envelopes will be used for randomisation. Neonates of multiple pregnancies will be considered as separate individuals.
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
Phase
Phase 3 / Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The primary end point is time to full enteral feeds (TFF) of 150 ml/kg/day. The current TFF (Mean +/- Std. Dev.) in neonates <28 weeks is 24 +/- 14.8 days. To demonstrate a 30% reduction in the TFF in the single vs. 3 strain probiotic group with 80% power and alpha 0.05 requires 75 neonates per group. To allow for attrition (15%) this will be increased to a total sample size of 172.

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)
WA
Recruitment hospital [1] 3524 0
King Edward Memorial Hospital - Subiaco
Recruitment postcode(s) [1] 9287 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 290832 0
Charities/Societies/Foundations
Name [1] 290832 0
Telethon and Channel 7 trust
Address [1] 290832 0
Roberts road, Subiaco, WA, 6008
Country [1] 290832 0
Australia
Funding source category [2] 291141 0
Charities/Societies/Foundations
Name [2] 291141 0
Princess Margaret Hospital Foundation
Address [2] 291141 0
Roberts road, Subiaco, 6008
Country [2] 291141 0
Australia
Primary sponsor type
Individual
Name
Gayatri Jape
Address
Department of Neonatal Paediatrics
King Edward Memorial Hospital
Bagot road
Subiaco, 6008
Country
Australia
Secondary sponsor category [1] 289523 0
None
Name [1] 289523 0
None
Address [1] 289523 0
NA
Country [1] 289523 0
Other collaborator category [1] 278369 0
University
Name [1] 278369 0
University of Western Australia
Address [1] 278369 0
35, Stirling highway
Crawley, 6009
Perth, Western Australia
Country [1] 278369 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292454 0
Womens and Newborns Health Reseacrh Ethics Committee
Ethics committee address [1] 292454 0
Princess Margaret Hospital, CCRF buliding, Roberts road, SUbiaco, WA, 6008
Ethics committee country [1] 292454 0
Australia
Date submitted for ethics approval [1] 292454 0
03/03/2015
Approval date [1] 292454 0
14/04/2015
Ethics approval number [1] 292454 0
2015019EW

Summary
Brief summary
Probiotics are live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host. Probiotics have been proven to reduce necrotizing enterocolitis, a devastating and life threatening emergency in neonates. Over recent years, the role of probiotics in improving gut motility and function has emerged. Probiotics, especially specific strains could improve nutrition in neonates by improving tolerance of oral feeds. Intolerance or poor tolerance of feeds along with repeated infections are some of the factors contributing to malnutrition in these high risk infants. Prevention of nutrition related issues in newborns will improve their long term development as well as their growth.
We propose to compare single strain probiotic as compared to multiple strain probiotic for their ability to improve oral feed tolerance in neonates. We will be administering either the single strain or multi strain probiotic after allotting the infant into either one or the other group and then examine the baby’s stool for presence of these good bacteria (contained in the probiotic). We will also be looking at the complex genetic structure of the bacteria in stool and study if probiotics could change the bad bacteria to good beneficial ones.
We will enrol all newborns less than 28 weeks of gestation, after parental consent. The probiotic supplements will be administered to the baby after starting oral feeds and continued till the baby is near term (37 weeks of gestation). Since probiotics improve intestinal motility, we will be investigating whether multiple strain probiotic will improve it to a better extent as compared to single strain probiotic. We will administer a small amount of dye orally to the infant and observe its excretion into stools. The better the effect on gut motility, the faster will be the excretion and shorter will be the time to excrete the dye as well.
In summary, this project will help us to conclude whether multiple strain probiotic will be more beneficial as compared to single strain for routine use in this high risk population.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55374 0
Dr Gayatri Jape
Address 55374 0
Department of Neonatal Paediatrics
King Edward Memorial Hospital
A block, first floor
374, Bagot road, Subiaco
WA, 6008
Country 55374 0
Australia
Phone 55374 0
+61893401260
Fax 55374 0
Email 55374 0
gayatri.jape@health.wa.gov.au
Contact person for public queries
Name 55375 0
Prof Karen Simmer
Address 55375 0
Department of Neonatal Paediatrics
King Edward Memorial Hospital
A block, first floor
374, Bagot road, Subiaco
WA, 6008
Country 55375 0
Australia
Phone 55375 0
+61893401260
Fax 55375 0
Email 55375 0
karen.simmer@health.wa.gov.au
Contact person for scientific queries
Name 55376 0
Prof Sanjay Patole
Address 55376 0
Department of Neonatal Paediatrics
King Edward Memorial Hospital
A block, first floor
374, Bagot road, Subiaco
WA, 6008
Country 55376 0
Australia
Phone 55376 0
+61893401260
Fax 55376 0
Email 55376 0
sanjay.patole@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Currently due to paucity of research support staff, it will be challenging to provide IPD information, also genomics and bolomics data is pending analysis.
What supporting documents are/will be available?
Study protocol
Clinical study report
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary