Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000508875
Ethics application status
Approved
Date submitted
31/03/2021
Date registered
30/04/2021
Date last updated
17/03/2024
Date data sharing statement initially provided
30/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of domperidone on breast milk supply following preterm birth- the SUMMIT study
Scientific title
SUpporting Mothers Milk Intervention Trial (SUMMIT)- A randomized controlled trial comparing different doses of domperidone for treating lactation insufficiency in mothers of preterm infants
Secondary ID [1] 303138 0
None
Universal Trial Number (UTN)
U1111-1263-7250
Trial acronym
SUMMIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lactation insufficiency 320254 0
Preterm birth 321752 0
Condition category
Condition code
Reproductive Health and Childbirth 318187 318187 0 0
Breast feeding
Reproductive Health and Childbirth 319492 319492 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Domperidone - 20 mg capsule administered orally three times daily (total daily dose = 60 mg/day)

Participants will initially commence on a low dose (10 mg three times daily, 30 mg/day) for 2 day before increasing to 60 mg/day for a further 19 days.

Total duration of intervention is 21 days.

Participants will then be provided the option of tapering their dose to twice daily for four days, and then once daily for three days, before stopping.

Medication adherence will be assessed using pill counts.
Intervention code [1] 319448 0
Treatment: Drugs
Comparator / control treatment
Domperidone - 10 mg capsule administered orally three times daily (total daily dose = 30 mg/day)

Total duration of intervention is 21 days.

Participants will then be provided the option of tapering their dose to twice daily for four days, and then once daily for three days, before stopping.

Medication adherence will be assessed using pill counts.
Control group
Dose comparison

Outcomes
Primary outcome [1] 326173 0
Daily breast milk volume. Identified from expressed volume recorded over a 24-hour period using a breast milk diary completed by mothers.
Timepoint [1] 326173 0
Day 21 of intervention
Secondary outcome [1] 390366 0
Maternal adverse events will be assessed using a study-specific questionnaire with reference to known/possible adverse events including dry mouth, headache, abdominal pain/cramping, rash, restlessness/trouble sleeping, heart palpitations, dizziness or weight gain.
Timepoint [1] 390366 0
From first study dose up to 28 days post-intervention commencement
Secondary outcome [2] 393521 0
Infant adverse events will be assessed using a study-specific questionnaire with reference to possible adverse events including: cardiac arrhythmia, sepsis, intra-ventricular haemorrhage (IVH), necrotising enterocolitis (NEC), and death,
Timepoint [2] 393521 0
From first study dose up to 28 days post-intervention commencement
Secondary outcome [3] 393522 0
Use and volume of supplementation to mother's own breast milk, such as formula or donor breast milk, extracted from infant medical records
Timepoint [3] 393522 0
Day 21 of intervention and at infant discharge from hospital or infant term corrected age (if this occurs before discharge)
Secondary outcome [4] 393523 0
Proportion breastfeeding or breast milk feeding (defined as the process of feeding a mother's breast milk to her infant, either directly from the breast or by expressing the milk from the breast and bottle-feeding it to the infant), collected through maternal self-report and case note review.
Timepoint [4] 393523 0
At infant discharge from hospital or infant term corrected age (if this occurs before discharge)
Secondary outcome [5] 393526 0
Duration of breastfeeding or breast milk feeding (defined as the process of feeding a mother's breast milk to her infant, either directly from the breast or by expressing the milk from the breast and bottle-feeding it to the infant), collected through maternal self-report and case note review.
Timepoint [5] 393526 0
Until infant discharge from hospital or infant term corrected age (if this occurs before discharge)
Secondary outcome [6] 393528 0
Mean daily breast milk volume using a breast milk diary completed by the mother
Timepoint [6] 393528 0
From day 0 to 21 of intervention
Secondary outcome [7] 393552 0
Total breast milk volume assessed using a breast milk diary completed by the mother
Timepoint [7] 393552 0
Day 0 to day 21 of intervention
Secondary outcome [8] 394743 0
Maternal prolonged corrected QT (QTc) interval, assessed using 12-lead electrocardiogram (ECG) by study research staff and defined as > 470 ms
Timepoint [8] 394743 0
Between day 7 to 14 post-intervention commencement

Eligibility
Key inclusion criteria
-Mothers of preterm infants born <34 weeks' gestation (up to 33+6)
-Lactation insufficiency defined as breast milk volume less than 300 mL/day in previous 24 hours if between 7 and 13 days postpartum, or breast milk volume less than 500 mL/day in previous 24 hours if between 14 and 28 days postpartum.
-Between 7 and 28 days postpartum
-Expressing with an electric pump an average of 6 times a day or more in previous 24-48 hours
-Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessment and follow-up of mother and baby until infant discharge.
-Signed and written consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Evidence of current Q-Tc prolongation (according to screening ECG)
- Already taking domperidone
- Allergy to domperidone
- History of known or suspected cardiac dysrhythmias (tachyarrhythmia, Q-Tc prolongation) or currently on an anti-arrhythmic medication
- Currently experiencing mastitis
- Previous breast surgery, including augmentation or reduction, nipple piercing
- Known chronic renal or hepatic impairment
- Contraindication to breastfeeding (e.g., HIV)
- Known to have a prolactin-releasing pituitary tumor
- Currently taking medications known to alter the metabolism and pharmacokinetics of domperidone and cause Q-Tc prolongation (e.g., oral azole antifungals, erythromycin antibiotics)
- Higher order pregnancies (triplet, or more)

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation will follow a computer generated randomisation schedule using randomly permuted blocks. Randomisation stratified by study centre.
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
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A sample size of 170 women (85 per arm) yields 90% power to show a difference in the mean daily breast milk volume of 100 mL/day between the high and low dose domperidone groups, allowing for a 10% loss to follow-up. This is based on a type I error rate of 5% and an estimated standard deviation of 190 mL.

The primary analysis will be performed according to the treatment group to which participants were randomised (intention-to-treat principle). A secondary per-protocol analysis will also be performed for each of the primary and secondary outcomes.

The primary outcome of daily breast milk volume on day 21 will be compared between treatment groups using a linear regression. The results will be expressed as a difference in means with a 95% confidence interval and two-sided p-value. Adjustment will be made for baseline breast milk volume and the randomization strata (study centre). A p-value of less than 0.05 will be considered to indicate statistical significance. Analysis of secondary outcomes will use log-binomial regression models for binary outcomes and linear regression models for continuous outcomes with adjustment for stratification variables and other pre-specified prognostic baseline variables. Results will be presented as relative risks and differences in means respectively, along with 95% confidence intervals. Missing data will be addressed using multiple imputation. Sensitivity analyses will also be performed using the original unimputed data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2022
Actual
27/09/2022
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
30/10/2025
Actual
Sample size
Target
170
Accrual to date
29
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 18387 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [2] 18388 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 21848 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [4] 23549 0
The Royal Women's Hospital - Parkville
Recruitment hospital [5] 23550 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 32477 0
5006 - North Adelaide
Recruitment postcode(s) [2] 32478 0
5042 - Bedford Park
Recruitment postcode(s) [3] 36905 0
3084 - Heidelberg
Recruitment postcode(s) [4] 38971 0
3052 - Parkville
Recruitment postcode(s) [5] 38972 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 307542 0
Government body
Name [1] 307542 0
National Health and Medical Research Council
Country [1] 307542 0
Australia
Funding source category [2] 307618 0
Charities/Societies/Foundations
Name [2] 307618 0
The Hospital Research Foundation
Country [2] 307618 0
Australia
Primary sponsor type
Other Collaborative groups
Name
South Australian Health and Medical Research Institute
Address
North Terrace
Adelaide 5000
South Australia
Country
Australia
Secondary sponsor category [1] 308240 0
None
Name [1] 308240 0
Address [1] 308240 0
Country [1] 308240 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307608 0
Women's and Children's Health Network Human Research Ethics Committee
Ethics committee address [1] 307608 0
Women's and Children's Hospital
72 King William Road
North AdelaideSA 5006
Ethics committee country [1] 307608 0
Australia
Date submitted for ethics approval [1] 307608 0
25/09/2019
Approval date [1] 307608 0
09/09/2020
Ethics approval number [1] 307608 0
HREC/19/WCHN/149
Ethics committee name [2] 311954 0
Mercy Health Human Research Ethics Committee
Ethics committee address [2] 311954 0
Mercy Hospitals Victoria Ltd Level 2, 12 Shelley Street Richmond Vic 3121
Ethics committee country [2] 311954 0
Australia
Date submitted for ethics approval [2] 311954 0
16/11/2021
Approval date [2] 311954 0
10/02/2022
Ethics approval number [2] 311954 0
2021-065

Summary
Brief summary
Mothers of preterm infants often struggle to produce enough breast milk to meet the daily feed requirements of their infants, especially in the longer-term. This randomized multi-centre double-blind parallel controlled trial will resolve the issue of whether a higher dose of domperidone (60 mg/day) leads to greater improvements in maternal breast milk supply compared to a lower dose (30 mg/day), while also evaluating differences in adverse events, impacts on breast milk composition, and identifying predictors of treatment response to domperidone.

Eligible women will be randomised to a high dose (60 mg/day) or low dose (30 mg/day) domperidone for 21 days. All women will initially commence on the low dose for 2-days before continuing with their assigned treatment dose for a further 19 days. The primary outcome will be assessed at day 21 following treatment initiation. After this point in time, women will be provided with the option to taper their dose to twice daily for four days and then once daily for three days, before stopping.

All participants will undertake regular study assessments including at baseline (study enrolment), day 7, 14, 21 of treatment, one-week following intervention, and at infant discharge to home or term corrected (whichever comes first). Women will undergo a breast assessment by a lactation consultant or nurse/midwife, and complete a breast milk diary throughout the study. Women will regularly undertake questionnaires evaluating demographics and lifestyle, breast health, milk expression, postnatal health, mental health and wellbeing, and infant feeding practices. Women will provide breast milk, blood, urine, stool and buccal cell swab samples.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107846 0
A/Prof Luke Grzeskowiak
Address 107846 0
College of Medicine and Public Health
Flinders University
GPO Box 2100, Adelaide 5001, South Australia
Country 107846 0
Australia
Phone 107846 0
+61 423 554 614
Fax 107846 0
Email 107846 0
[email protected]
Contact person for public queries
Name 107847 0
A/Prof Luke Grzeskowiak
Address 107847 0
College of Medicine and Public Health
Flinders University
GPO Box 2100, Adelaide 5001, South Australia
Country 107847 0
Australia
Phone 107847 0
+61 423 554 614
Fax 107847 0
Email 107847 0
[email protected]
Contact person for scientific queries
Name 107848 0
A/Prof Luke Grzeskowiak
Address 107848 0
College of Medicine and Public Health
Flinders University
GPO Box 2100, Adelaide 5001, South Australia
Country 107848 0
Australia
Phone 107848 0
+61 423 554 614
Fax 107848 0
Email 107848 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Baseline Characteristics: including demographics, age and study-specific measures for all participants, after de-identification.
Outcome data: all of the individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Beginning 3 months following main results publication; no end date determined
Available to whom?
To researchers who provide a methodologically sound proposal, and on a case-by-case basis at the discretion of Primary Sponsor.
Available for what types of analyses?
For IPD meta-analyses.
How or where can data be obtained?
Access subject to approvals by Principal Investigator ([email protected]).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10285Study protocol  [email protected]
11234Informed consent form  [email protected]
11235Ethical approval  [email protected]



Results publications and other study-related documents

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