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

NCT ID: NCT06088849

Last Updated: 2024-07-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-20

Study Completion Date

2023-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Feeding Hypertension Heart Failure Proteinuria

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Lactating mothers taking ACE-inhibitors

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

Group Type OTHER

Venipuncture

Intervention Type 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).

Interventions

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Venipuncture

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).

Intervention Type PROCEDURE

Other Intervention Names

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Venipuncture infant

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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KU Leuven

OTHER

Sponsor Role collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kristel Van Calsteren, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Locations

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Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, Belgium

Site Status

Countries

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Belgium

References

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

Reference Type BACKGROUND
PMID: 29411152 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21940904 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25690342 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1602396 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16756089 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30723406 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11030016 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23269526 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23887688 (View on PubMed)

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

Reference Type BACKGROUND

Related Links

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Other Identifiers

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S65657

Identifier Type: -

Identifier Source: org_study_id

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