ANZCTR - Registration

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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

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]

Nil known

Secondary ID [2]

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

gut colonisation

faecal short chain fatty acids

Condition category

Condition code

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Diet and Nutrition

Other diet and nutrition disorders

Reproductive Health and Childbirth

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]

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]

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]

from commencement of enteral feeds till 37 completed weeks of gestation

Secondary outcome [1]

All-cause mortality(clinical notes review within 1 month of mortality)

Timepoint [1]

within 3-4 months of discharge from the hospital

Secondary outcome [2]

Gut flora and stool colonisation (assayed by conventional stool culture methods)

Timepoint [2]

after completion of enrolment, preferably 3-4 months post discharge from hospital

Secondary outcome [3]

duration of parenteral nutrition (by review of inbuilt data available in our neonatal database)

Timepoint [3]

during patient stay in hospital or post discharge, within 3-4 months of patient discharge

Secondary outcome [4]

Necrotizing enterocolitis (NEC)
(assayed by clinical record review)

Timepoint [4]

after patient discharge, within 3-4 months following discharge of a patient

Secondary outcome [5]

Incidence of Late onset sepsis (assayed by blood tests and clinical examination)

Timepoint [5]

after patient discharge, within 3-4 months following pateint discharge

Secondary outcome [6]

NEC related mortality (by review of medical records)

Timepoint [6]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/09/2015

Actual

2/09/2015

Date of last participant enrolment

Anticipated

Actual

16/05/2017

Date of last data collection

Anticipated

Actual

28/02/2018

Sample size

Target

172

Accrual to date

Final

172

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

King Edward Memorial Hospital - Subiaco

Recruitment postcode(s) [1]

6008 - Subiaco

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Telethon and Channel 7 trust

Address [1]

Roberts road, Subiaco, WA, 6008

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Princess Margaret Hospital Foundation

Address [2]

Roberts road, Subiaco, 6008

Country [2]

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]

None

Name [1]

None

Address [1]

Country [1]

Other collaborator category [1]

University

Name [1]

University of Western Australia

Address [1]

35, Stirling highway
Crawley, 6009
Perth, Western Australia

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Womens and Newborns Health Reseacrh Ethics Committee

Ethics committee address [1]

Princess Margaret Hospital, CCRF buliding, Roberts road, SUbiaco, WA, 6008

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

03/03/2015

Approval date [1]

14/04/2015

Ethics approval number [1]

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

Dr Gayatri Jape

Address

Department of Neonatal Paediatrics
King Edward Memorial Hospital
A block, first floor
374, Bagot road, Subiaco
WA, 6008

Country

Australia

Phone

+61893401260

Fax

gayatri.jape@health.wa.gov.au

Contact person for public queries

Name

Karen Simmer

Address

Department of Neonatal Paediatrics
King Edward Memorial Hospital
A block, first floor
374, Bagot road, Subiaco
WA, 6008

Country

Australia

Phone

+61893401260

Fax

karen.simmer@health.wa.gov.au

Contact person for scientific queries

Name

Sanjay Patole

Address

Department of Neonatal Paediatrics
King Edward Memorial Hospital
A block, first floor
374, Bagot road, Subiaco
WA, 6008

Country

Australia

Phone

+61893401260

Fax

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?

Current supporting documents:

Updated to:

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
23373	Other			gayatri.jape@health.wa.gov.au	published manuscript	368079-(Uploaded-25-07-2024-12-02-00)-bmjgast-2021-000811.pdf
23374	[Marked for deletion] Clinical study report			gayatri.jape@health.wa.gov.au

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Current Status of Probiotics for Preterm Infants.	2021	https://dx.doi.org/10.1007/s12098-021-03736-2
Embase	Effect of single versus multistrain probiotic in extremely preterm infants: A randomised trial.	2022	https://dx.doi.org/10.1136/bmjgast-2021-000811

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically