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Trial registered on ANZCTR


Registration number
ACTRN12617001401347
Ethics application status
Approved
Date submitted
28/09/2017
Date registered
4/10/2017
Date last updated
10/05/2021
Date data sharing statement initially provided
18/09/2019
Date results information initially provided
10/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Probiotics for newborn babies with surgical conditions of the gut
Scientific title
Probiotic supplementation in neonates with major gastrointestinal surgical conditions: A Pilot Randomized Double Blind Placebo Controlled Trial
Secondary ID [1] 292964 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
PRINS Trial (Probiotics In Neonatal Surgery)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major congenital gastrointestinal anomalies 304862 0
Condition category
Condition code
Oral and Gastrointestinal 304169 304169 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Surgery 304170 304170 0 0
Other surgery
Reproductive Health and Childbirth 304274 304274 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 (1×109 Colony Forming Units of each strain per 1 g sachet: Probiotic group).
Supplementation protocol: As soon as possible after admission, enrolled neonates will be supplemented with freshly reconstituted contents of the allocated sachets every day, and continued until discharge.
Reconstitution of the dry powder in the sachets will be done using sterile water for injection or breast milk. Care will be taken during reconstitution to reduce the risk of cross contamination by adhering to strict hand hygiene. The dose will be 3×109 CFU/day ( i.e. 3 billion organisms per day) in 1.5 ml of the reconstituted solution, given as a single daily dose via the orogastric/nasogastric feeding tube or orally. Supplementation will be continued until discharge from the neonatal unit. The principal investigator will monitor the medication charts of study infants to ensure adherence to the intervention.
Intervention code [1] 299202 0
Treatment: Other
Comparator / control treatment
Placebo: Dextrin. The contents of the sachet will be diluted in 1.5 ml of the reconstituted solution and given as a single daily dose via the orogastric/nasogastric feeding tube or orally. Supplementation will be continued until discharge from the neonatal unit.
Control group
Placebo

Outcomes
Primary outcome [1] 303483 0
Primary outcomes: Gut microbiota (using 16 s r RNA Pyrosequencing studies for phylogenic profiling) on the stool samples
Timepoint [1] 303483 0
On the stool samples collected a. as soon as possible after admission, but prior to the commencement of supplementation b) 7-9 days after commencement of supplementation, c) 14-16 days after commencement of supplementation, and d) prior to discharge from the neonatal unit (in those who stay more than 4 weeks after commencing supplementation). This amendment to the protocol was approved by the institutional HREC on 25 January 2018.
Secondary outcome [1] 339043 0
Stool Short Chain Fatty Acids (SCFA) assay using gas chromatography
Timepoint [1] 339043 0
On the stool samples collected a. as soon as possible after admission, but prior to the commencement of supplementation b) 7-9 days after commencement of supplementation, c) 14-16 days after commencement of supplementation, and d) prior to discharge from the neonatal unit (in those who stay more than 4 weeks after commencing supplementation). This amendment to the protocol was approved by the institutional HREC on 25 January 2018.
Secondary outcome [2] 339329 0
Blood culture positive sepsis
Timepoint [2] 339329 0
During initial hospitalisation
Secondary outcome [3] 339330 0
Duration of antibiotic therapy
Timepoint [3] 339330 0
During initial hospitalisation
Secondary outcome [4] 339331 0
Duration of hospital stay (days)
Timepoint [4] 339331 0
During initial hospitalisation
Secondary outcome [5] 339332 0
Time (days) to achieve full enteral feeds of 120 ml/kg/day.
Timepoint [5] 339332 0
During initial hospitalisation

Eligibility
Key inclusion criteria
(1) Neonates (>=35 weeks gestation) with the following major congenital gastrointestinal anomalies: Intestinal Atresia (duodenal, jejunal, ileal or colonic), Intestinal Malrotation, Tracheo-Oesophageal fistula, Oesphageal atresia, Gastroschisis, Exompholos, Congenital Diaphragmatic Hernia, Meconium ileus or peritonitis requiring laparotomy, Hirschsprung Disease, Anal atresia, Impeforate anus, Short Bowel Syndrome, and any surgical condition needing the creation of small or large intestinal stoma (eg severe meconium ileus, micro-colon).
Minimum age
0 Days
Maximum age
4 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Non gastrointestinal surgical conditions. (2) Neonates born at <35 weeks' gestation

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)
Allocation concealment will be optimized by using pharmacy controlled allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Group assignment will be allocated by a computer generated randomization sequence in randomly ordered block sizes of 2 and 4.
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
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Continuous variables will be compared using the t test for normally distributed data and Wilcoxon rank sum test for skewed data. Categorical variables will be compared using the fisher’s exact test. Logistic regression analysis will be used for analysis of binary outcomes (primary outcome of interest) to derive Relative Risk and 95% confidence intervals. Linear regression analysis will be used for continuous outcomes to derive regression coefficients and respective confidence intervals. A p value of <0.05 will be considered statistically significant.

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] 9098 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 17595 0
6009 - Nedlands
Recruitment postcode(s) [2] 17597 0
6009 - Broadway Nedlands

Funding & Sponsors
Funding source category [1] 297591 0
University
Name [1] 297591 0
Centre for Neonatal Research and Education, University of Western Australia
Address [1] 297591 0
374 Bagot Road, King Edward Memorial Hospital for Women, Subiaco, Western Australia, 6008
Country [1] 297591 0
Australia
Primary sponsor type
Hospital
Name
Princess Margaret Hospital for Children
Address
1 Roberts Road, Subiaco, Western Australia, 6008
Country
Australia
Secondary sponsor category [1] 296605 0
Hospital
Name [1] 296605 0
Perth Children's Hospital
Address [1] 296605 0
Hospital Avenue, Nedlands, WA, 6009
Country [1] 296605 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298682 0
Child and Adolescent Health Service
Ethics committee address [1] 298682 0
Princess Margaret Hospital for Children, Subiaco, Western Australia, 6008
Ethics committee country [1] 298682 0
Australia
Date submitted for ethics approval [1] 298682 0
11/07/2016
Approval date [1] 298682 0
23/05/2017
Ethics approval number [1] 298682 0
2016086EP

Summary
Brief summary
Newborn babies with serious surgical conditions of the gut are admitted to intensive care units, undergo surgery, and receive intravenous drips and strong antibiotics. The administration of breast milk is often delayed in these infants. All these factors interfere with the normal development of healthy bacteria in their intestines and enhance the proliferation of harmful bacteria. Such an imbalance between healthy and unhealthy bacteria in the gut can be harmful to the health and well-being of these babies. In this study, we plan to give healthy bacteria called probiotics orally for 30 surgical newborn babies and placebo for 30 surgical newborn babies to see if probiotics help improve their intestinal bacteria and overall health. The results of this study will help us design a much larger study in the future. If that larger study confirms the benefits, probiotics will then be used routinely for all newborn babies with surgical conditions of the gut.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77878 0
A/Prof Shripada Rao
Address 77878 0
Neonatal Intensive Care Unit, Perth Children's Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia
Country 77878 0
Australia
Phone 77878 0
+61 864565393
Fax 77878 0
+61864562080
Email 77878 0
shripada.rao@health.wa.gov.au
Contact person for public queries
Name 77879 0
A/Prof Shripada Rao
Address 77879 0
Neonatal Intensive Care Unit, Princess Margaret Hospital for Children, Roberts Road, Subiaco, WA, 6008, Australia
Country 77879 0
Australia
Phone 77879 0
+61 864565393
Fax 77879 0
+61864562080
Email 77879 0
shripada.rao@health.wa.gov.au
Contact person for scientific queries
Name 77880 0
A/Prof Shripada Rao
Address 77880 0
Neonatal Intensive Care Unit, Princess Margaret Hospital for Children, Roberts Road, Subiaco, WA, 6008, Australia
Country 77880 0
Australia
Phone 77880 0
+61 864565393
Fax 77880 0
+61864562080
Email 77880 0
shripada.rao@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
At this stage, we have not applied for permission for IPD sharing from our HREC. In future, if there is a reasonable HREC approved request from systematic reviewers, we will discuss with our HREC prior to sharing IPD.
What supporting documents are/will be available?
No other documents available
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?
Results – basic reporting
Results – plain English summary