Maternal and Fetal/Neonatal Pharmacokinetics and - Dynamics of Corticosteroids During Pregnancy

Preterm Birth Clinical Trial

— MaDyCo  

Official title:

Maternal and Fetal/Neonatal Pharmacokinetics and - Dynamics of Corticosteroids During Pregnancy as Treatment for Fetal Lung Maturation MaDyCo-study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06264973
• Other study ID #: NL9318
• Status: Recruiting
• Start date: January 1, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: February 2024
• Source: Erasmus Medical Center
• Contact: Sam Schoenmakers, MD, PhD
• Phone: 0031107037439
• Email: s.schoenmakers[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Improving pregnancy outcome is essential in improving health of both parents and their offspring during the life course. Preterm birth (PTB) occurs in 10-15% of all pregnancies, is the leading cause of perinatal mortality and morbidity {Goldenberg, 2008}, has long-term adverse consequences for postnatal health {Huddy, 2001} and is a burden for health care expenditure. In order to improve neonatal outcome, antenatal corticosteroids (ACS) are routinely administered to women at risk for preterm delivery before 34 weeks of pregnancy. {Jobe, 2018;Roberts, 2017;Travers, 2018} However, the current, worldwide standard of care, for the use of ACS is still based on animal experiments performed in the 1970's. {Liggins, 1969} Although ACS treatment to improve neonatal outcome was clinically introduced in the 70's, still only two dosing regimens are used, neither of which have been investigated, re-evaluated or refined to determine the optimal doses or treatment interval. With the current health care approach of personalized medicine in mind, the same universal approach for everybody, independent of gestational age, number of fetus, maternal weight or comorbidity one dose does not fit all since it often has not the desired effect. Due to the lack of optimization of the above mentioned synthetic corticosteroid drug regimens {Kemp, 2019}, significant gaps in knowledge exist. An important aspect to set up, investigate and understand dosing and also dosing interval experiments, is knowledge of the maternal individual pharmacokinetics and pharmacogenetics of the drug of interest during pregnancy.

Description:

A clinical observational study will be performed in women admitted at the Department of Obstetrics at the Sophia Children's Hospital/Erasmus MC for suspicion of preterm birth with a gestational age of 23+5 weeks until 33+6 weeks. Antenatal corticosteroids will be administered according to the local standard protocol (12 mg betamethasone intramuscular with a 24 hours intervall). Importantly, clinical management of women with suspicion of preterm birth will not be affected by the proposed study. After inclusion, repetitive blood sampling according to the following schedule: t0 (administration), t0-30 min, t10-12hrs and t20-24 hrs. Umbilical cord will be sampled directly after birth as fetal determinant in which corticosteroids and their metabolites will be measured. Also, neonatal blood samples (drawn by the paediatricians as part of standard care) will be used for measurement of corticosteroids and their metabolites. Maternal blood samples will furthermore be analysed for determinants effecting pharmacokinetics such as oestradiol.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 1, 2025
• Est. primary completion date: June 1, 2025
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Older than 18 years of age.

2. Admitted at the Department of Obstetrics at Erasmus MC - Sophia for suspicion of preterm birth with a gestational age of 23+5 weeks until 33+6 weeks.

3. Understanding of Dutch in speaking and reading.

4. Written informed consent.

In order for the neonate to be able to participate in this study, the parent must meet the following criteria:

5. Older than 18 years of age.

6. Admitted at the Department of Obstetrics at Erasmus MC - Sophia for suspicion of preterm birth with a gestational age of 23+5 weeks until 33+6 weeks.

7. Understanding of Dutch in speaking and reading.

8. Written informed consent for the neonate.

Exclusion Criteria:

1. Women unable or unwilling to agree with the procedures.

2. Women unable or unwilling to give written informed consent.

3. Women with acute obstetric complications requiring immediate delivery at time of admission.

Related Conditions & MeSH terms

• Premature Birth
• Preterm Birth

Locations

Country	Name	City	State
Netherlands	Erasmus Medical Center	Rotterdam	Zuid Holland

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CYP3A4 level	To examine the relation between CYP3A4 genotype and the pharmacokinetics of the primary objective	2 days
Primary	Pharmacokinetics of antenatal corticosteroids by investigation of betamethasone concentrations in serum	To examine the pharmacokinetics in maternal blood of standard regimen at the Erasmus MC of two doses of 12 mg betamethasone intramuscular with a 24 hours interval	2 days
Secondary	Maternal age	To examine the relation between maternal age and the pharmacokinetics of the primary objective	2 days
Secondary	Fetal sex	To examine the relation between fetal sex and the pharmacokinetics of the primary objective	2 days
Secondary	Maternal weight/BMI	To examine the relation between maternal weight/BMI and the pharmacokinetics of the primary objective	2 days
Secondary	Number of fetus	To examine the relation between the number of fetus and the pharmacokinetics of the primary objective	2 days
Secondary	Parity: the number of times a woman has given birth to a live neonate (any gestation) or at 24 weeks or more	To examine the relation between parity the pharmacokinetics of the primary objective	2 days
Secondary	PE by urine measurement of protein-creatinine ratio	To examine the relation between pre-eclampsia and the pharmacokinetics of the primary objective	2 days
Secondary	Oestradiol concentration in serum	To examine the relation between oestradiol on pharmacokinetics of the primary objective	2 days
Secondary	Cord blood and neonatal blood	To examine the relation between pharmacokinetics in cord blood and neonatal blood	Delivery