Enhancing Breast Milk Production With Domperidone in Mothers of Preterm Neonates (EMPOWER)

• ClinicalTrials.gov Identifier: NCT01512225
• Recruitment Status: Completed
• First Posted: January 19, 2012
• Results First Posted: April 20, 2017
• Last Update Posted: April 20, 2017
• Sponsor: Sunnybrook Health Sciences Centre
• Information provided by (Responsible Party): Sunnybrook Health Sciences Centre

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Low Milk Supply	Drug: Domperidone maleate; Drug: Placebo Tablet	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Enhancing Breast Milk Production With Domperidone in Mothers of Preterm Neonates
• Study Start Date: May 2012
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: March 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Domperidone for days 1 to 28; Domperidone maleate tablets 10 mg orally three times daily from days 1 to 28	Drug: Domperidone maleate; domperidone maleate tablet 10 mg orally three times daily for 28 days
Placebo Comparator: Placebo for days 1 to 14 and domperidone for day 15-28; 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; placebo tablet 10 mg orally three times daily for 14 days; Drug: Domperidone maleate; domperidone maleate tablet 10 mg orally three times daily for 14 days

Outcome Measures

Primary Outcome Measures :

1. Increase in Breast Milk Production [ Time Frame: 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 Outcome Measures :

1. Increase in Breast Milk Volume on Day 28 [ Time Frame: day 0 to day 28 ]
   Number of mothers who achieved 50% increase in milk volume on day 28
2. Mean Breast Milk Volumes on Day 14 [ Time Frame: Day 0 and day 14 ]
   Mean milk volumes between the two groups at 14 days of study intervention
3. Mean Breast Milk Volumes on Day 28 [ Time Frame: day 0 and 28 ]
   Mean milk volumes between the two groups at 28 days of study intervention
4. Mean Volume Change From Day 0 to Day 14 [ Time Frame: days 0 and 14 ]
   change on the volume of milk from day 0 to day 14 between the two groups
5. Mean Volume Change on the Volume of Milk From Day 15 to Day 28 [ Time Frame: day 15 and day 28 ]
   change on the volume of milk from day 15 to day 28 between the two groups
6. Provision of Breast Milk at Term Gestation [ Time Frame: term gestation ]
   provision of breast milk as the primary source of nutrition
7. Provision of Breast Milk at 6 Weeks Post Term Gestation [ Time Frame: 6 weeks post term gestation ]
   Provision of breast milk at 6 weeks post term gestation as primary source of nutrition

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5

Sponsors and Collaborators

Sunnybrook Health Sciences Centre

Investigators

• Principal Investigator: Elizabeth V Asztalos, MD; Sunnybrook Research Institute
• Principal Investigator: Marsha Campbell-Yeo, PhD; IWK Health Centre
• Principal Investigator: Orlando Da Silva, MD; Children's Hospital, London Health Sciences Centre

More Information

Publications of Results:

Asztalos EV, Campbell-Yeo M, da Silva OP, Ito S, Kiss A, Knoppert D; EMPOWER Study Collaborative Group. Enhancing Human Milk Production With Domperidone in Mothers of Preterm Infants. J Hum Lact. 2017 Feb;33(1):181-187. doi: 10.1177/0890334416680176. Epub 2017 Jan 20.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Asztalos EV, Kiss A, daSilva OP, Campbell-Yeo M, Ito S, Knoppert D; EMPOWER Study Collaborative Group. Role of days postdelivery on breast milk production: a secondary analysis from the EMPOWER trial. Int Breastfeed J. 2019 Jun 4;14:21. doi: 10.1186/s13006-019-0215-z. eCollection 2019.

Asztalos EV, Kiss A, daSilva OP, Campbell-Yeo M, Ito S, Knoppert D; <italic>EMPOWER</italic> Study Collaborative Group. Evaluating the Effect of a 14-Day Course of Domperidone on Breast Milk Production: A Per-Protocol Analysis from the EMPOWER Trial. Breastfeed Med. 2019 Mar;14(2):102-107. doi: 10.1089/bfm.2018.0175. Epub 2018 Dec 13.

Asztalos EV, Kiss A, da Silva OP, Campbell-Yeo M, Ito S, Knoppert D; EMPOWER Study Collaborative Group. Pregnancy gestation at delivery and breast milk production: a secondary analysis from the EMPOWER trial. Matern Health Neonatol Perinatol. 2018 Nov 5;4:21. doi: 10.1186/s40748-018-0089-x. eCollection 2018.

Asztalos EV, Campbell-Yeo M, daSilva OP, Kiss A, Knoppert DC, Ito S. Enhancing breast milk production with Domperidone in mothers of preterm neonates (EMPOWER trial). BMC Pregnancy Childbirth. 2012 Aug 31;12:87. doi: 10.1186/1471-2393-12-87.

• Responsible Party: Sunnybrook Health Sciences Centre
• ClinicalTrials.gov Identifier: NCT01512225
• Other Study ID Numbers: 232-2011
• First Posted: January 19, 2012
• Results First Posted: April 20, 2017
• Last Update Posted: April 20, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Sunnybrook Health Sciences Centre:

breastmilk; domperidone; preterm

Additional relevant MeSH terms:

Premature Birth; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Domperidone; Maleic acid; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Dopamine Antagonists; Dopamine Agents; Neurotransmitter Agents