Enhancing Breast Milk Production With Domperidone in Mothers of Preterm Neonates

Study Overview
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Brief Summary
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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
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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.

Official Title
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Enhancing Breast Milk Production With Domperidone in Mothers of Preterm Neonates

Conditions
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Low Milk Supply

Intervention / Treatment
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* Drug: Domperidone maleate
* Drug: Placebo Tablet
* Drug: Domperidone maleate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Domperidone for days 1 to 28<br>Domperidone maleate tablets 10 mg orally three times daily from days 1 to 28 | Drug: Domperidone maleate<br>* domperidone maleate tablet 10 mg orally three times daily for 28 days<br>|
| Placebo Comparator: Placebo for days 1 to 14 and domperidone for day 15-28<br>Identical placebo tablets 10 mg orally three times daily from days 1 to 14 followed by Domperidone maleate tablets 10 mg orally three times daily from days 15 to 28 | Drug: Placebo Tablet<br>* placebo tablet 10 mg orally three times daily for 14 days<br>Drug: Domperidone maleate<br>* domperidone maleate tablet 10 mg orally three times daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Day 0 to day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in Breast Milk Volume on Day 28 | Number of mothers who achieved 50% increase in milk volume on day 28 | day 0 to day 28 | 
| Mean Breast Milk Volumes on Day 14 | Mean milk volumes between the two groups at 14 days of study intervention | Day 0 and day 14 | 
| Mean Breast Milk Volumes on Day 28 | Mean milk volumes between the two groups at 28 days of study intervention | day 0 and 28 | 
| 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 | days 0 and 14 | 
| 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 | day 15 and day 28 | 
| Provision of Breast Milk at Term Gestation | provision of breast milk as the primary source of nutrition | term gestation | 
| 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 | 6 weeks post term gestation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breastmilk, domperidone, preterm