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Trial registered on ANZCTR


Registration number
ACTRN12624000704594
Ethics application status
Approved
Date submitted
7/04/2024
Date registered
4/06/2024
Date last updated
4/06/2024
Date data sharing statement initially provided
4/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Nutritional management of growth faltering in infants aged under six months in Asia and Africa (BRANCH, Breastfeeding counselling and management of growth)
Scientific title
Nutritional milk supplementation and breastfeeding counselling for growth faltering amongst infants aged under six months in Asia and Africa
Secondary ID [1] 311898 0
None
Universal Trial Number (UTN)
None
Trial acronym
BRANCH
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Faltering growth 333481 0
Condition category
Condition code
Diet and Nutrition 330157 330157 0 0
Other diet and nutrition disorders
Public Health 330589 330589 0 0
Health promotion/education

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Interventions for all infants - all infants in the intervention and comparator groups will receive visits for clinical assessment and management and intensive breastfeeding (BF) counselling and support . The first visit will be within 24 hours from the time growth faltering (GF) is identified. Subsequent visits will be on day 1, 3, 7 and then weekly until the GF has resolved. The visits will be approximately 30 mins duration and will be provided by a trained study team. The content will be:
- Clinical assessment of management of health by trained nurses and doctors using WHO Integrated Management of Childhood Illness materials https://iris.who.int/bitstream/handle/10665/326448/9789241516365-eng.pdf?sequence=1, and WHO Pocket Book of Hospital Care for Children materials https://iris.who.int/bitstream/handle/10665/81170/9789241548373_eng.pdf?sequence=1
adapted for local site specific requirements. There will also be referral to other health services if needed.
- Intensive BF counselling and support using the WHO Guideline: Counselling of women to improve breastfeeding practices https://iris.who.int/bitstream/handle/10665/280133/9789241550468-eng.pdf?sequence=1

The intervention group will receive visits for clinical assessment and management and intensive breastfeeding (BF) counselling and support on day 1,3,7 and then weekly until the GF has resolved as described above plus the study prescription of the nutritional milk supplement (NMS) . The details of the NMS are described below:

-Type of NMS - The NMS will be standard commercially available ‘term’ formula milk that meets Food and Drug Organization (FAO) and Codex Alimentarius (https://www.fao.org/fao-who-codexalimentarius/sh-proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%252Fsites%252Fcodex%252FStandards%252FCXS%2B72-1981%252FCXS_072e.pdf ) requirements for formula milk for infants aged 0 to < 6 months. The NMS will be procured by UNICEF in six sites (Bangladesh, Ethiopia, Nigeria, Pakistan, Tanzania, Uganda) and there will be incountry procurement in one site (India) due to country regulations.

- Method of NMS provision - The responsive feeding method will be used to provide the NMS to the infant. i.e. ‘responsive NMS feeding’ will be provided . WHO and UNICEF define responsive feeding as recognizing the infants’ cues for feeding, closeness and comfort, and responding accordingly to these cues. Mothers will be trained and counselled in the responsive NMS feeding by the supplement team using the methods described in the WHO publication https://iris.who.int/bitstream/handle/10665/259386/9789241550086-eng.pdf?sequence=1 . The mother will be advised to give the NMS only after full support for breastfeeding has been provided i.e. after breastfeeding. The Infant will be offered the NMS feeds at least 6 times a day, and whenever the Infant is cueing or appears hungry. The infant will be fed according to infant’s cues and will not be force-fed or tube-fed. If the Infant is cueing and still appears hungry after the NMS is finished then the infant will be offered additional NMS and as much NMS as the infant wishes

-NMS amount – To calculate the minimum amount of NMS to be offered to the infant at each feed, the minimum amount of energy (kilo calories, kcals) required for catch up growth ( called in this trial the ‘catch up calories’) will be calculated using guidelines adapted from ESPGHAN (European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) 2005:41;S5–S11 https://journals.lww.com/jpgn/fulltext/2005/11002/ 2__energy.2.aspx and FAO/WHO/UNU (Food and Agriculture Organization of the United Nations/World Health Organization/United Nations University) 2004. Human energy requirements. https://www.fao.org/4/y5686e/y5686e05.htm . The standard energy requirement (SER) for infants aged 0 to < 6 months of 100 kcals/kg.day will be multiplied by the ratio of the ‘target weight’ (TW*) divided by the ‘actual weight’ (AW*) as defined below. (i.e. catch up calories = SER x TW/AW) . The calculated ‘catch up calories’ will then be multiplied by the kcals / ml specified in the product specifications (67 kcals/100mls for the Unicef procured NMS) to provide the minimum mls/kg/day of NMS to be provided to the infant.

-Frequency – The NMS will be offered to the infant at least six times per day, and as many times as the Infant demands. The infant’s cues will be monitored carefully by the mother and additional feeds will be offered as soon as the infant cues indicate.

-NMS preparation. The NMS will be prepared according to manufacturers’ instructions. Mothers will be shown how to prepare the NMS and counselled on safe preparation and techniques using standard WHO guidance https://www.who.int/publications/i/item/9789241595414 adapted for local site specific requirements. Mothers will also be advised on the risks of diarrhoeal illness and will be given clear guidance on seeking medical care early.

-Monitoring and review – The infant will be reviewed on day 1, 3, 7 and then weekly until the infant reaches the recovery point. Adherence to both the breastfeeding support and the NMS will be monitored by the trial data management system (number and duration of visits and intake of the NMS)..

Recovery point and stopping the NMS - The NMS will be provided until the infant has reached the recovery point* i.e. the infant has regained their ‘healthy centile’ (as defined below*) and maintained it for eight weeks. The NMS will be stopped at that time and the infant will resume standard BF counselling and support and 2 weekly growth monitoring.

*Definitions for NMS provision used in this trial are as follows:
-‘actual weight’ = weight of the infant at the time of the assessment
-‘target weight’ = weight at which the infant has regained their ‘healthy centile’ in 4 weeks
-‘healthy centile’ = weight for age centile / z score before growth problems started
Intervention code [1] 328368 0
Treatment: Other
Intervention code [2] 328675 0
Behaviour
Comparator / control treatment
The comparator group will receive the same visits as the intervention group (for clinical assessment and management and intensive breastfeeding counselling and support on day 1,3,7 and then weekly until the growth faltering has resolved) but the infants in the comparator group will not receive the study prescription of nutritional milk supplement (NMS).
Control group
Active

Outcomes
Primary outcome [1] 337914 0
Wasting free survival at 6 completed months of age = composite outcome = all cause mortality or wasting (wasting is defined as weight for length z score less than 2 standard deviation (sd) scores below the median of the WHO Growth Standards).
Timepoint [1] 337914 0
6 completed months of age (chronological age).
Secondary outcome [1] 433686 0
Wasting at 6 completed months of age = weight for length z-score < - 2 standard deviations (SD) from the median of the WHO Growth Standards
Timepoint [1] 433686 0
6 completed months of age (chronological age).
Secondary outcome [2] 435519 0
Underweight at 6 completed months of age = weight-for-age z-score < - 2 standard deviations (SD) from the median of the WHO Growth Standards
Timepoint [2] 435519 0
6 completed months of age (chronological age).
Secondary outcome [3] 435520 0
Stunting at 6 completed months of age = length for age z-score < - 2 standard deviations (SD) from the median of the WHO Growth Standards
Timepoint [3] 435520 0
6 completed months of age (chronological age).
Secondary outcome [4] 435521 0
Concurrent wasting and stunting at 6 completed months of age = composite measure of wasting and/or stunting as defined above
Timepoint [4] 435521 0
6 completed months of age (chronological age).
Secondary outcome [5] 435522 0
All-cause mortality from enrolment to 6 completed months of age
Timepoint [5] 435522 0
6 completed months of age (chronological age).
Secondary outcome [6] 435523 0
At least one hospitalisation for any cause from enrolment to 6 completed months of age
Timepoint [6] 435523 0
6 completed months of age (chronological age).
Secondary outcome [7] 435524 0
At least one hospitalisation for diarrhoea from enrolment to 6 completed months of age
Timepoint [7] 435524 0
6 completed months of age (chronological age).
Secondary outcome [8] 435525 0
At least one hospitalisation for pneumonia from enrolment to 6 completed months of age
Timepoint [8] 435525 0
6 completed months of age (chronological age).
Secondary outcome [9] 435526 0
At least one hospitalisation for other infections from enrolment to 6 completed months of age
Timepoint [9] 435526 0
6 completed months of age (chronological age).
Secondary outcome [10] 435527 0
At least one hospitalisation for all other causes from enrolment to 6 completed months of age
Timepoint [10] 435527 0
6 completed months of age (chronological age).
Secondary outcome [11] 435528 0
At least one report of care-seeking for illness from enrolment to 6 completed months of age. Care seeking is defined as seeking care for illness from a health care facility, pharmacist or drug seller (or the local term that is used for pharmacist or drug seller).
Timepoint [11] 435528 0
6 completed months of age.

Eligibility
Key inclusion criteria
-Age of baby > = 7 and < 14 days
-Ultrasound-based gestational age before 20 weeks of gestation is available
-Baby is 28 weeks gestation or more
-Birth weight taken within 72 hours after birth
-Baby has been fed breastmilk at any time since birth
Minimum age
7 Days
Maximum age
13 Days
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
-The biological mother is dead at the time of screening
-Baby has a major abnormality or condition which is impairing feeding or nutrition (such as severe cleft palate, severe asphyxia, severe respiratory distress syndrome, need for mechanical ventilation, severe necrotising enterocolitis, major surgery)
-Family does not intend to live in the study area for six months
-The mother has given birth to three or more babies (ie twins are included but triplets or quadruplets etc are excluded)
-A baby from the same household is currently part of the study (i.e. is being visited by the study team).

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)
Yes, central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation, using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2024
Actual
Date of last participant enrolment
Anticipated
30/11/2025
Actual
Date of last data collection
Anticipated
31/07/2026
Actual
Sample size
Target
9900
Accrual to date
Final
Recruitment outside Australia
Country [1] 26233 0
Bangladesh
State/province [1] 26233 0
Country [2] 26234 0
India
State/province [2] 26234 0
Country [3] 26235 0
Pakistan
State/province [3] 26235 0
Country [4] 26236 0
Ethiopia
State/province [4] 26236 0
Country [5] 26237 0
Nigeria
State/province [5] 26237 0
Country [6] 26238 0
Tanzania, United Republic Of
State/province [6] 26238 0
Country [7] 26239 0
Uganda
State/province [7] 26239 0

Funding & Sponsors
Funding source category [1] 316249 0
Charities/Societies/Foundations
Name [1] 316249 0
Bill and Melinda Gates Foundation
Country [1] 316249 0
United States of America
Primary sponsor type
Other
Name
World Health Organization
Address
Country
Switzerland
Secondary sponsor category [1] 318435 0
None
Name [1] 318435 0
Address [1] 318435 0
Country [1] 318435 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315067 0
World Health Organization (WHO) Ethics Review Committee (ERC)
Ethics committee address [1] 315067 0
20 Avenue Appia, Geneva, Switzerland, 1202
Ethics committee country [1] 315067 0
Switzerland
Date submitted for ethics approval [1] 315067 0
18/07/2023
Approval date [1] 315067 0
28/08/2023
Ethics approval number [1] 315067 0
WHO ERC.0003754

Summary
Brief summary
The overall aim of this trial is to determine the effect of nutritional milk supplementation (NMS) plus intensive breastfeeding support compared with intensive breastfeeding support alone on mortality, morbidity and growth in infants aged 0-6 months with growth faltering in South Asia and Sub-Saharan Africa. The primary hypothesis is to predict whether there is an effect of nutritional milk supplementation in infants with growth faltering aged under 6 months. The NMS will be provided as standard term formula and prescribed for each infant in the intervention group by a dedicated trial supplementation team.
Trial website
Trial related presentations / publications
Public notes
There is an additional registration for this trial for the India site only with the CTRI. Registration number CTRI/2022/07/043716.

Contacts
Principal investigator
Name 133570 0
Dr Karen Edmond
Address 133570 0
World Health Organization, Av Appia 20, 1202 Geneva, Switzerland
Country 133570 0
Switzerland
Phone 133570 0
+41795839349
Fax 133570 0
Email 133570 0
edmondk@who.int
Contact person for public queries
Name 133571 0
Karen Edmond
Address 133571 0
World Health Organization, Av Appia 20, 1202 Geneva, Switzerland
Country 133571 0
Switzerland
Phone 133571 0
+41795839349
Fax 133571 0
Email 133571 0
edmondk@who.int
Contact person for scientific queries
Name 133572 0
Karen Edmond
Address 133572 0
World Health Organization, Av Appia 20, 1202 Geneva, Switzerland
Country 133572 0
Switzerland
Phone 133572 0
+41795839349
Fax 133572 0
Email 133572 0
edmondk@who.int

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Only data dictionaries which do not have IPD data will be shared
When will data be available (start and end dates)?
Only data dictionaries which do not have IPD data will be shared. The data dictionaries will be able to be requested for 10 years from the end of the study.
Available to whom?
Other researchers only.
Available for what types of analyses?
Only data dictionaries which do not have IPD data will be shared, they will be available on request to the trial sponsor.
How or where can data be obtained?
edmondk@who.int


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
22123Study protocol    Will be submitted to a peer reviewed journal



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.