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Trial registered on ANZCTR


Registration number
ACTRN12615000923561
Ethics application status
Approved
Date submitted
16/07/2015
Date registered
4/09/2015
Date last updated
27/08/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
APProve: CAn Probiotics ImPROVE Breastfeeding Outcomes?
Scientific title
Evaluation of the probiotic Lactobacillus Fermentum CECT5716 for the prevention of mastitis in breastfeeding women: a randomised controlled trial
Secondary ID [1] 287077 0
Nil
Universal Trial Number (UTN)
Trial acronym
APProve
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mastitis 295580 0
Condition category
Condition code
Reproductive Health and Childbirth 295854 295854 0 0
Breast feeding
Inflammatory and Immune System 295969 295969 0 0
Normal development and function of the immune system
Infection 295970 295970 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The participant will be given an 8 week supply of the probiotic sachets containing Lactobacillus Fermentum (1x10^10 CFU/mL). Participants will be advised to take one sachet daily for a period of 8 weeks following the birth of her baby. The contents of the sachet should be mixed with water, juice or milk, stirred and consumed immediately. The number of unused sachets will be collected by the research coordinator at the end of the 8 week period.

Daily data on treatment intake, breast pain, infection symptoms and infant feeding will be collected by participants via the mobile phone application system (APP). Weekly questionnaires will collect data on maternal and infant well-being, unscheduled doctor’s visits, and medication intake. Women not using the mobile phone application system will receive a 2 month calendar diary to record her daily responses, along with a weekly questionnaire accessed by an emailed web-link. For all participants, follow-up questionnaires will be sent at 2, 6 and 12 months to collect secondary outcomes.
Intervention code [1] 292314 0
Treatment: Other
Intervention code [2] 292406 0
Prevention
Comparator / control treatment
The participant will be given an 8 week supply of the placebo sachets which are identical in every way to the treatment sachets but do not contain the active Lactobacillus fermentum ingredient. Participants will be advised to take one sachet daily for a period of 8 weeks following the birth of her baby. The contents of the sachet should be mixed with water, juice or milk, stirred and consumed immediately. The number of unused sachets will be collected by the research coordinator at the end of the 8 week period.

Daily data on treatment intake, breast pain, infection symptoms and infant feeding will be collected by participants via the mobile phone application system (APP). Weekly questionnaires will collect data on maternal and infant well-being, unscheduled doctor’s visits, and medication intake. Women not using the mobile phone application system will receive a 2 month calendar diary to record her daily responses, along with a weekly questionnaire accessed by an emailed web-link. For all participants, follow-up questionnaires will be sent at 2, 6 and 12 months to collect secondary outcomes.
Control group
Placebo

Outcomes
Primary outcome [1] 295564 0
The primary outcome will be incidence of mastitis up to 8 weeks following delivery as measured by:
1. Clinical diagnosis of mastitis
OR
2. At least two of the following breast symptoms:
*Pain
*Redness / inflammation
*Lump / swelling
AND at least one of the following systemic symptoms:
*flu-like symptoms (body aches, headaches and chills)
*fever greater or equal to 38 degrees C
(Above symptoms must present for at least 24 hours - i.e. recorded for 2 or more consecutive days on the mobile phone application system or calendar diary.)
Timepoint [1] 295564 0
Within 8 weeks following delivery.
Secondary outcome [1] 315860 0
Length of time breastfeeding assessed by patient surveys designed specifically for this study.
Timepoint [1] 315860 0
Daily and weekly x 8 weeks and at 2, 6, and 12 months postpartum.
Secondary outcome [2] 316095 0
Breastfeeding complications assessed by patient surveys designed specifically for this study. Examples include development of breast abscess, cracked nipples, or recurrence of mastitis.
Timepoint [2] 316095 0
Daily and weekly x 8 weeks, then at 2, 6 and 12 months postpartum.
Secondary outcome [3] 316096 0
Overall maternal health and well-being assessed by patient surveys including SF-12 Quality of Life Questionnaire and the State-Trait Anxiety Inventory (STAI-6), as well as surveys designed specifically for this study. Examples include number of doctor’s visits, adverse effects of treatment, incidence of primary mastitis, and postpartum use of antibiotics.
Timepoint [3] 316096 0
Weekly x 8 weeks and at 2, 6 and 12 weeks postpartum.
Secondary outcome [4] 316097 0
Acceptability and compliance of trial using a mobile phone application system assessed by patient surveys and comparative data collection between APP and non-APP users. The surveys have been designed specifically for this study.
Timepoint [4] 316097 0
2 months postpartum.
Secondary outcome [5] 316099 0
Preference for method of postnatal questionnaires assessed by tick-box of patient preference. Examples include postal or web-link.
Timepoint [5] 316099 0
2, 6 and 12 months postpartum.
Secondary outcome [6] 316100 0
Infant health and well-being measured by patient surveys designed specifically for this study. Examples include: gastroenteritis, growth and development in the first year of life (infant weight and measurements), doctor’s visits, infections, admission to hospital, allergic reactions, and use of antibiotics.
Timepoint [6] 316100 0
Weekly x 8 weeks and at 2, 6 and 12 weeks postpartum.

Eligibility
Key inclusion criteria
Pregnant women at least 18 years of age at 37 weeks gestation or later with a singleton pregnancy will be invited to participate in the trial. They will currently not be taking commercial probiotics containing lactobacillus fermentum; and will own a smartphone. Their intention at the time of consent will be to breastfeed their baby.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Women with a history of Raynaud syndrome will not be eligible to participate in the trial. Any delivery/breast complication rendering the infant unable to breastfeed will be excluded. Women unable to speak/understand English will not be consented.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible women will be identified and approached by a local researcher on the postnatal ward within 72 hours of delivery. The researcher will explain the trial, review the Patient Information Sheet, obtain informed consent and collect baseline data. The participant will then be randomised to either “probiotic” or “placebo” and provided with the study intervention.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will be prepared and centrally administered by a researcher not involved in patient care. A computer random number generator will be used to prepare the randomisation schedule in blocks, stratified by previous mastitis and sequentially numbered opaque envelopes will be used to ensure allocation concealment. The randomisation sequence will be concealed until all data has been collected. The participant and researcher will be blinded as to treatment allocation.
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 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size is based on an expected rate of mastitis in the control group of 18%, two-sided 5% significance level and a power of 80%, we estimated a total sample size of 452 would be required. However, given studies related to the duration of breastfeeding report a cessation rate in the first 8 weeks post-partum of up to 20%, and a potential loss-to follow-up of 5-10% may occur with withdrawals or non-compliance, we inflated the sample size by a further 30% to ensure complete data. Hence, we estimated a total sample size of approximately 600 women would be required (300 per group) for this trial.

Primary and secondary outcomes will be analysed using an intention-to-treat approach, which includes all losses-to follow-up, non-compliances or withdrawals.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/04/2015
Actual
21/04/2015
Date of last participant enrolment
Anticipated
30/11/2016
Actual
1/12/2016
Date of last data collection
Anticipated
Actual
31/05/2017
Sample size
Target
600
Accrual to date
Final
639
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4054 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 11738 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 11739 0
Royal Hospital for Women - Randwick
Recruitment postcode(s) [1] 23820 0
2031 - Randwick
Recruitment postcode(s) [2] 23819 0
2050 - Camperdown
Recruitment postcode(s) [3] 9981 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 291652 0
University
Name [1] 291652 0
Perinatal Research Group, Kolling Institute, University of Sydney
Country [1] 291652 0
Australia
Funding source category [2] 291653 0
Commercial sector/Industry
Name [2] 291653 0
Puremedic Pty Ltd.
Country [2] 291653 0
Australia
Funding source category [3] 291654 0
Commercial sector/Industry
Name [3] 291654 0
Ramsay Research and Teaching Fund
Country [3] 291654 0
Australia
Primary sponsor type
University
Name
Perinatal Research Group, Kolling Institute, University of Sydney
Address
Perinatal Research Group
Level 2, Building 52, RNSH
Reserve Road
St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 290321 0
None
Name [1] 290321 0
Address [1] 290321 0
Country [1] 290321 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293179 0
Northern Sydney Local Health District HREC
Ethics committee address [1] 293179 0
Kolling Building, Level 13
Royal North Shore Hospital
Reserve Road
St Leonards NSW 2065
Ethics committee country [1] 293179 0
Australia
Date submitted for ethics approval [1] 293179 0
Approval date [1] 293179 0
24/11/2014
Ethics approval number [1] 293179 0
HREC/14/HAWKE/358

Summary
Brief summary
The primary aim of the project is to evaluate the effectiveness of oral probiotics for the prevention of mastitis in lactating women. Secondary aims will assess maternal breastfeeding outcomes, infant infections including
gastroenteritis, and the acceptability of a novel mobile app.
The primary hypothesis is that regular ingestion of probiotics by women in the first two months following birth will decrease the incidence of mastitis in lactating women.
The secondary hypotheses are that exposure to probiotics may also confer a benefit to breastfeeding mothers and
reduce risk of infection among infants, particularly gastroenteritis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58746 0
Prof Natasha Nassar
Address 58746 0
Level 2, Charles Perkins Centre D17, The University of Sydney NSW 2006
Country 58746 0
Australia
Phone 58746 0
+61 2 9036 7006
Fax 58746 0
Email 58746 0
natasha.nassar@sydney.edu.au
Contact person for public queries
Name 58747 0
Mrs Diana Bond
Address 58747 0
Level 2, Charles Perkins Centre D17, The University of Sydney NSW 2006
Country 58747 0
Australia
Phone 58747 0
+61 2 9036 7006
Fax 58747 0
Email 58747 0
diana.bond@sydney.edu.au
Contact person for scientific queries
Name 58748 0
Prof Natasha Nassar
Address 58748 0
Level 2, Charles Perkins Centre D17, The University of Sydney NSW 2006
Country 58748 0
Australia
Phone 58748 0
+61 2 9036 7006
Fax 58748 0
Email 58748 0
natasha.nassar@sydney.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseStudy protocol: Evaluation of the probiotic Lactobacillus Fermentum CECT5716 for the prevention of mastitis in breastfeeding women: A randomised controlled trial.2017https://dx.doi.org/10.1186/s12884-017-1330-8
N.B. These documents automatically identified may not have been verified by the study sponsor.