Maternal Treatment With ACE-inhibitors and Breastfeeding: a Mono-centric Study on the Exposure Through Breast Milk

Study Overview
=================
Brief Summary
-----------------
The ACE-inhibitors is one group of essential medication for which reliable data on the safety during breastfeeding is lacking. ACE inhibitors are indicated for several severe or life-threatening disorders like hypertension, heart failure or nephrotic range proteinuria and diabetic nephropathy. However, data on the transfer of ACE inhibitors into the human breast milk remains very limited. After delivery, ACE inhibitor therapy is often postponed if the mother is breastfeeding, requiring multiple other medications to control the disease, or switched from long to short acting forms, decreasing therapeutic adherence. Limited available data shows that the transfer of ACE-inhibitors into the milk is probably low, and thus that ACE-inhibitor are likely to be safe during breastfeeding. The objective of this trial is to collect information about the breast milk transfer, and subsequent infant exposure and general health outcome to selected maternal medication (ACE inhibitors) in patients from UZ Leuven. Furthermore, we will also use these data to verify the predictive performance of physiologically-based pharmacokinetic models to predict breast milk and subsequent neonatal exposure to maternal medication during lactation. The medicines that will be investigated are perindopril, captopril, cilazapril, enalapril, fosinopril, lisinopril, quinapril, ramipril and zofenopril. The investigators will enroll +/-10 mothers, who have been prescribed ACE inhibitors for medical reasons and are breastfeeding their infant while taking this medication.The mother will be asked to collect milk samples during 24 h and 2 blood samples: one at the time of milk pumping the first time after medication intake, and one at the last pumping session of the 24 h. Furthermore, we will ask the parents if we can collect a blood sample of the child (1mL/kg, and max 2,5mL). In addition, clinical maternal and infant variables will be collected, as well as medication intake, sampling information and general infant health. To conclude, with this study we hope to generate human data about the use of ACE inhibitors during breastfeeding. This information is an essential first step towards evidence-based risk assessment on the use of these drugs during lactation.

Official Title
-----------------
Maternal Treatment With ACE-inhibitors and Breastfeeding: a Mono-centric Study on the Exposure Through Breast Milk

Conditions
-----------------
Breast Feeding, Hypertension, Heart Failure, Proteinuria

Intervention / Treatment
-----------------
* Procedure: Venipuncture


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For lactating mothers Lactating 0-6 months postpartum Age: ≥18 year On steady state ACE-inhibitor therapy, for any indication (e.g. perindopril, captopril, cilazapril, enalapril, fosinopril, lisinopril, quinapril, ramipril & zofenopril) Willing to express breast milk Informed consent to participate and for processing their personal data For neonates/infants 0-6 months of age at inclusion of the mother Postmenstrual age: ≥ 37 weeks In case of blood sampling: exclusively breastfed at the time of sampling Parental informed consent to participate and for processing their personal data Exclusion Criteria: Participation in a trial with an investigational product within the previous three months Not meeting the inclusion criteria

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: We will enroll mothers who have been prescribed ACE-inhibitors for medical reasons and are breastfeeding their infant while taking this medication. The mother will be asked to collect milk samples and donate 2 blood samples during a 24h period. Furthermore, we will ask the parents if we can collect a blood sample of the child. In addition, clinical maternal and infant variables will be collected, as well as medication intake, sampling information and general infant health.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Lactating mothers taking ACE-inhibitors<br>Lactating mothers who are breastfeeding their infant (0-6 months) while taking ACE-inhibitors. | Procedure: Venipuncture<br>* The lactating mother will be asked to collect milk samples and donate 2 blood samples, which is not a part of their normal follow-up/treatment. We will also aks the parents if we can collect a blood sample fo the infant (0-6 months).<br>* Other names: Venipuncture infant;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secretion rates of ACE-inhibitors into the human breast milk | The maternal plasma concentration, milk-to-plasma ratios fo the selected medicines, PK parameters of the parent medication and metabolites in mature breast milk, such as area under the milk concentration-time curve (AUC), the average concentration, peak and trough milk concentrations and time to reach peak milk concentration. | 24 hours (sampling day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The child's systemic exposure after exposure to ACE-inhibitors via breastfeeding | The infant's plasma concentration of ACE-inhibitors (if a blood sample of the infant is obtained), the relevant infant dose, the daily infant dose, the infant/maternal plasma ratio (if a blood sample of the neonate is obtained) after exposure to maternal ACE-inhibitors via breastfeeding. | during the sampling day (24 hours) | 
| The child's outcome after exposure to ACE-inhibitors via breastfeeding | The health condition of the infants after exposure to maternal ACE-inhibitors via breastfeeding. | Up to 2 months after inclusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Angiotensin-converting-enzyme inhibitor