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

NCT06088849 | Completed

• 1 other identifier: S65657
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Feeding; Hypertension; Heart Failure; Proteinuria

Keywords

Angiotensin-converting-enzyme inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• The child's systemic exposure after exposure to ACE-inhibitors via breastfeeding

  during the sampling day (24 hours)

• The child's outcome after exposure to ACE-inhibitors via breastfeeding

  Up to 2 months after inclusion

Study Arms (1)

Lactating mothers taking ACE-inhibitors

OTHER

Lactating mothers who are breastfeeding their infant (0-6 months) while taking ACE-inhibitors.

Procedure: Venipuncture

Interventions

Venipuncture PROCEDURE

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).

Also known as: Venipuncture infant

Lactating mothers taking ACE-inhibitors

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For lactating mothers
• Lactating
• 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
• 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

You may not qualify if:

• Participation in a trial with an investigational product within the previous three months

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• KU Leuven: collaborator

Study Sites (1)

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Related Publications (10)

• Anderson PO. Drugs in Lactation. Pharm Res. 2018 Feb 6;35(3):45. doi: 10.1007/s11095-017-2287-z.

  PMID: 29411152 BACKGROUND

• Koshimichi H, Ito K, Hisaka A, Honma M, Suzuki H. Analysis and prediction of drug transfer into human milk taking into consideration secretion and reuptake clearances across the mammary epithelia. Drug Metab Dispos. 2011 Dec;39(12):2370-80. doi: 10.1124/dmd.111.040972. Epub 2011 Sep 22.

  PMID: 21940904 BACKGROUND

• Ito N, Ito K, Ikebuchi Y, Toyoda Y, Takada T, Hisaka A, Oka A, Suzuki H. Prediction of Drug Transfer into Milk Considering Breast Cancer Resistance Protein (BCRP)-Mediated Transport. Pharm Res. 2015 Aug;32(8):2527-37. doi: 10.1007/s11095-015-1641-2. Epub 2015 Feb 19.

  PMID: 25690342 BACKGROUND

• McNamara PJ, Burgio D, Yoo SD. Pharmacokinetics of cimetidine during lactation: species differences in cimetidine transport into rat and rabbit milk. J Pharmacol Exp Ther. 1992 Jun;261(3):918-23.

  PMID: 1602396 BACKGROUND

• Kimura S, Morimoto K, Okamoto H, Ueda H, Kobayashi D, Kobayashi J, Morimoto Y. Development of a human mammary epithelial cell culture model for evaluation of drug transfer into milk. Arch Pharm Res. 2006 May;29(5):424-9. doi: 10.1007/BF02968594.

  PMID: 16756089 BACKGROUND

• Garessus EDG, Mielke H, Gundert-Remy U. Exposure of Infants to Isoniazid via Breast Milk After Maternal Drug Intake of Recommended Doses Is Clinically Insignificant Irrespective of Metaboliser Status. A Physiologically-Based Pharmacokinetic (PBPK) Modelling Approach to Estimate Drug Exposure of Infants via Breast-Feeding. Front Pharmacol. 2019 Jan 22;10:5. doi: 10.3389/fphar.2019.00005. eCollection 2019.

  PMID: 30723406 BACKGROUND

• Piepho RW. Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1;57 Suppl 1:S3-7. doi: 10.1093/ajhp/57.suppl_1.S3.

  PMID: 11030016 BACKGROUND

• Jones HM, Mayawala K, Poulin P. Dose selection based on physiologically based pharmacokinetic (PBPK) approaches. AAPS J. 2013 Apr;15(2):377-87. doi: 10.1208/s12248-012-9446-2. Epub 2012 Dec 27.

  PMID: 23269526 BACKGROUND

• Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacometrics Syst Pharmacol. 2013 Apr 17;2(4):e38. doi: 10.1038/psp.2013.14. No abstract available.

  PMID: 23887688 BACKGROUND

• FDA. Clinical Lactation Studies: Considerations for Study Design Guidance for Industry DRAFT GUIDANCE. May 2019.

  BACKGROUND

Related Links

• Breastfeeding

MeSH Terms

Conditions

Breast Feeding; Hypertension; Heart Failure; Proteinuria

Interventions

Phlebotomy

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Kristel Van Calsteren, MD PhD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 6, 2022
• First Posted: October 18, 2023
• Study Start: December 20, 2021
• Primary Completion: December 30, 2023
• Study Completion: December 31, 2023
• Last Updated: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)