Breast FeedingNCT06088849
Maternal Treatment With ACE-inhibitors and Breastfeeding: a Mono-centric Study on the Exposure Through Breast Milk
A study testing Venipuncture in people with Breast Feeding and Hypertension, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Feeding, Hypertension, Heart Failure
- What is being tested?
- Venipuncture
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteBelgium
- Study dates
- 20 Dec 2021to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- Participation in a trial with an investigational product within the previous three months
- Not meeting the inclusion criteria
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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
- Being tested
- Venipuncture
- Keywords
- Angiotensin-converting-enzyme inhibitor
- Medical subject headings
- Breast Feeding, Hypertension, Heart Failure, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenipunctureProcedure or surgery
Also called Venipuncture infant
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).
| Study group | Role | What they receive |
|---|---|---|
| Lactating mothers taking ACE-inhibitors | Other | Lactating mothers who are breastfeeding their infant (0-6 months) while taking ACE-inhibitors. Receives: Procedure: Venipuncture |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours (sampling day)
Secondary outcomes (2)
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.
Measured: 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.
Measured: Up to 2 months after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2023
- Study start20 Dec 2021
- Primary completion30 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Breast FeedingStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven
- Responsible party
- Sponsor
- Investigators
- Kristel Van Calsteren, MD PhD, Principal investigator, Universitaire Ziekenhuizen KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06088849
- Sponsor's protocol ID
- S65657
- Status last verified
- Jun 2024
- First submitted
- 6 May 2022
- Last updated
- 1 Jul 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Anderson PO. Drugs in Lactation. Pharm Res. 2018 Feb 6;35(3):45. doi: 10.1007/s11095-017-2287-z.
PubMed 29411152Koshimichi 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.
PubMed 21940904Ito 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.
PubMed 25690342McNamara 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.
PubMed 1602396Kimura 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.
PubMed 16756089Garessus 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.
PubMed 30723406Piepho 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.
PubMed 11030016Jones 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.
PubMed 23269526Mould 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.
PubMed 23887688FDA. Clinical Lactation Studies: Considerations for Study Design Guidance for Industry DRAFT GUIDANCE. May 2019.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maternal Treatment With ACE-inhibitors and Breastfeeding: a Mono-centric Study on the Exposure Through Breast Milk
- ClinicalTrials.gov ID
- NCT06088849
- Acronym / sponsor ID
- S65657
- Conditions
- Breast Feeding, Hypertension, Heart Failure, Proteinuria
- Keywords
- Angiotensin-converting-enzyme inhibitor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- KU Leuven
- Study start
- 20 Dec 2021 (actual)
- Primary completion
- 30 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 18 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Lactating mothers taking ACE-inhibitors | Other | Procedure: VenipunctureLactating mothers who are breastfeeding their infant (0-6 months) while taking ACE-inhibitors. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
Key exclusion criteria (2 listed)
- Participation in a trial with an investigational product within the previous three months
- Not meeting the inclusion criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenipunctureAlso: Venipuncture infantThe 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). | Procedure or surgery | Lactating mothers taking ACE-inhibitors |
Primary outcome
The secretion rates of ACE-inhibitors into the human breast milk
Time frame: 24 hours (sampling day)
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.
2 secondary outcomes
The child's systemic exposure after exposure to ACE-inhibitors via breastfeeding
Time frame: during the sampling day (24 hours)
The child's outcome after exposure to ACE-inhibitors via breastfeeding
Time frame: Up to 2 months after inclusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2024.
- Background: PubMed 29411152Anderson PO. Drugs in Lactation. Pharm Res. 2018 Feb 6;35(3):45. doi: 10.1007/s11095-017-2287-z.
- Background: PubMed 21940904Koshimichi 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.
- Background: PubMed 25690342Ito 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.
- Background: PubMed 1602396McNamara 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.
- Background: PubMed 16756089Kimura 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.
- Background: PubMed 30723406Garessus 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.
- Background: PubMed 11030016Piepho 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.
- Background: PubMed 23269526Jones 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.
- Background: PubMed 23887688Mould 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.
- BackgroundFDA. Clinical Lactation Studies: Considerations for Study Design Guidance for Industry DRAFT GUIDANCE. May 2019.
- BreastfeedingLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristel Van Calsteren, MD PhD principal investigator
Universitaire Ziekenhuizen KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Venipuncture in people with Breast Feeding and Hypertension, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The secretion rates of ACE-inhibitors into the human breast milk (time frame: 24 hours (sampling day)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06088849, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2024.