Low Milk Supply
Conditions
Keywords
breastmilk, domperidone, preterm
Brief summary
The purpose of this study is to evaluate the safety and efficacy of Domperidone in those mothers who are identified as having difficulty with breast milk production to meet the nutritional needs of their infant in the neonatal intensive are unit hospitalization setting, and to determine how it should be considered in the care of mothers and their preterm infants without causing undesirable effects to either the mother or infant.
Detailed description
It is widely acknowledged that recent perinatal and neonatal technological advances (eg. assisted ventilation, surfactant, antenatal corticosteroids) have greatly enhanced the survival rate of very low birth weight and extremely low birth weight infants. A compelling body of evidence now exists to suggest that use of breast milk to feed preterm infants during initial hospitalization positively impacts their neurodevelopment during early childhood and beyond. In order to provide breastmilk, mothers of preterm infants have to begin to produce and mechanically express milk. However, these mothers are often faced with challenges in maintaining an adequate volume that will meet their infants' nutritional needs, as well as declines in production after several weeks despite a myriad of measures designed to assist in production. The primary hypothesis for this study is that Domperidone, through its pharmacologic action on increasing prolactin levels, will assist mothers experiencing inadequate breast milk production in increasing breast milk volumes to a level identified as being sufficient for continued pumping in the hospitalization period.
Interventions
DRUGDomperidone maleate
domperidone maleate tablet 10 mg orally three times daily for 28 days
DRUGPlacebo Tablet
placebo tablet 10 mg orally three times daily for 14 days
Sponsors
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* mothers of a preterm infant born \< 30 completed weeks gestation (23 0/7-29 6/7 weeks) * postpartum period of 7-21 days * mechanically pumping a minimum average of 6 times a day in the 4-7 days prior to enrollment * experiencing inadequate milk supply defined as providing \< 100% of the average of the daily nutritional intake during the previous 72-hour period prior to enrollment based on a fluid intake of 250 mL/kg/d or experiencing a clinical reduction of approximately 20% from a peak volume during the previous 72-hour period prior to enrollment
Exclusion criteria
* 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 and/or the use of nipple rings/studs within the last year, or any reduction * known chronic or debilitating illness, known abnormal liver function or gastric abnormalities gastrointestinal that will be exacerbated by the use of a prokinetic, examples include hemorrhage or blockage, actively treated with acid reflux which requires treatment for greater than 5 days and includes H2 blockers (occasional use of H2 blockers for heartburn or mild acid reflux is not considered an exclusion) and HIV * known to have a prolactin-releasing pituitary tumor * receiving medications known to alter the metabolism and pharmacokinetics of domperidone (eg. oral azole antifungals, erythromycin antibiotics, monoamine oxidase inhibitors (MAO) inhibitors) or medications that have dopaminergic or antidopaminergic activity or affect prolactin levels * mothers of higher order pregnancies (triplet, or more) * currently smoking 6 or more cigarette per day as reported by the mother
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Increase in Breast Milk Production | Day 0 to day 14 | The primary outcome is the difference in the proportion of women having a 50% increase in breast milk volume at the end of 14 days of treatment with domperidone compared to mothers receiving placebo (mean day 14 volume minus mean day 0 volume at entry). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Breast Milk Volumes on Day 14 | Day 0 and day 14 | Mean milk volumes between the two groups at 14 days of study intervention |
| Mean Breast Milk Volumes on Day 28 | day 0 and 28 | Mean milk volumes between the two groups at 28 days of study intervention |
| Mean Volume Change From Day 0 to Day 14 | days 0 and 14 | change on the volume of milk from day 0 to day 14 between the two groups |
| Increase in Breast Milk Volume on Day 28 | day 0 to day 28 | Number of mothers who achieved 50% increase in milk volume on day 28 |
| Provision of Breast Milk at Term Gestation | term gestation | provision of breast milk as the primary source of nutrition |
| Provision of Breast Milk at 6 Weeks Post Term Gestation | 6 weeks post term gestation | Provision of breast milk at 6 weeks post term gestation as primary source of nutrition |
| Mean Volume Change on the Volume of Milk From Day 15 to Day 28 | day 15 and day 28 | change on the volume of milk from day 15 to day 28 between the two groups |
Countries
Canada
Participant flow
Recruitment details
Recruitment took place from June 1, 2012 to June 30, 2015 in 8 Neonatal Intensive Care Units in Canada
Pre-assignment details
Mothers could be identified in the NICU as early as day 4 until day 18 post-delivery. Additional counseling and support by the lactation consultant with respect to non-pharmacologic techniques were offered. If there was no response to the techniques, the mother was considered eligible for the trial.
Participants by arm
| Arm | Count |
|---|---|
| Group A: Domperidone Domperidone 10 mg orally three times daily for 28 days
Domperidone maleate: domperidone 10 mg orally three times daily for 28 days | 45 |
| Group B: Placebo + Domperidone Identical placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days
Domperidone maleate plus placebo: identical placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days | 45 |
| Total | 90 |
Baseline characteristics
| Characteristic | Group A: Domperidone | Group B: Placebo + Domperidone | Total |
|---|---|---|---|
| Age, Continuous | 31.25 years | 33.56 years | 32.41 years |
| Mean milk Volume at entry | 121 millilitres STANDARD_DEVIATION 96 | 115 millilitres STANDARD_DEVIATION 95 | 118 millilitres STANDARD_DEVIATION 96 |
| Parity 0 | 28 Participants | 33 Participants | 61 Participants |
| Parity >/= 1 | 17 Participants | 12 Participants | 29 Participants |
| Race/Ethnicity, Customized Aboriginal | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 8 Participants | 16 Participants |
| Race/Ethnicity, Customized Black | 6 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Caucasian | 29 Participants | 30 Participants | 59 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 45 Participants | 45 Participants | 90 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Type of pregnancy Singleton | 38 Participants | 39 Participants | 77 Participants |
| Type of pregnancy Twins | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 45 | 3 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 45 |
Outcome results
Primary
Increase in Breast Milk Production
The primary outcome is the difference in the proportion of women having a 50% increase in breast milk volume at the end of 14 days of treatment with domperidone compared to mothers receiving placebo (mean day 14 volume minus mean day 0 volume at entry).
Time frame: Day 0 to day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: Domperidone | Increase in Breast Milk Production | 35 Participants |
| Group B: Placebo + Domperidone | Increase in Breast Milk Production | 26 Participants |
Secondary
Increase in Breast Milk Volume on Day 28
Number of mothers who achieved 50% increase in milk volume on day 28
Time frame: day 0 to day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: Domperidone | Increase in Breast Milk Volume on Day 28 | 31 Participants |
| Group B: Placebo + Domperidone | Increase in Breast Milk Volume on Day 28 | 28 Participants |
Secondary
Mean Breast Milk Volumes on Day 14
Mean milk volumes between the two groups at 14 days of study intervention
Time frame: Day 0 and day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Domperidone | Mean Breast Milk Volumes on Day 14 | 267 millilitres | Standard Deviation 189 |
| Group B: Placebo + Domperidone | Mean Breast Milk Volumes on Day 14 | 217 millilitres | Standard Deviation 168 |
Secondary
Mean Breast Milk Volumes on Day 28
Mean milk volumes between the two groups at 28 days of study intervention
Time frame: day 0 and 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Domperidone | Mean Breast Milk Volumes on Day 28 | 290 millilitres | Standard Deviation 211 |
| Group B: Placebo + Domperidone | Mean Breast Milk Volumes on Day 28 | 302 millilitres | Standard Deviation 230 |
Secondary
Mean Volume Change From Day 0 to Day 14
change on the volume of milk from day 0 to day 14 between the two groups
Time frame: days 0 and 14
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group A: Domperidone | Mean Volume Change From Day 0 to Day 14 | 254 millilitres |
| Group B: Placebo + Domperidone | Mean Volume Change From Day 0 to Day 14 | 175 millilitres |
Secondary
Mean Volume Change on the Volume of Milk From Day 15 to Day 28
change on the volume of milk from day 15 to day 28 between the two groups
Time frame: day 15 and day 28
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group A: Domperidone | Mean Volume Change on the Volume of Milk From Day 15 to Day 28 | 22 millilitres |
| Group B: Placebo + Domperidone | Mean Volume Change on the Volume of Milk From Day 15 to Day 28 | 49 millilitres |
Secondary
Provision of Breast Milk at 6 Weeks Post Term Gestation
Provision of breast milk at 6 weeks post term gestation as primary source of nutrition
Time frame: 6 weeks post term gestation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: Domperidone | Provision of Breast Milk at 6 Weeks Post Term Gestation | 19 Participants |
| Group B: Placebo + Domperidone | Provision of Breast Milk at 6 Weeks Post Term Gestation | 20 Participants |
Secondary
Provision of Breast Milk at Term Gestation
provision of breast milk as the primary source of nutrition
Time frame: term gestation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: Domperidone | Provision of Breast Milk at Term Gestation | 26 Participants |
| Group B: Placebo + Domperidone | Provision of Breast Milk at Term Gestation | 27 Participants |