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 for pregnant women suspected of preterm birth with a gestational age between 23+5…
ID
Source
Brief title
Condition
- Pregnancy, labour, delivery and postpartum conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To examine the maternal and fetal (as measured in umbilical cord blood sampling
directly after birth) pharmacokinetics of standard regimen at the Erasmus MC of
two doses of 12 mg betamethasone intramuscular with a 24 hours interval for
pregnant women suspected of preterm birth with a gestational age between 23+5
until 33+6 weeks. Farmacokinetic parameters, which will be determined are:
distribution (VD), clearance (Cl), elimination-rate constant (kel),
steady-state concentration (Css), half-life (t1/2), bioavailability (F).
Secondary outcome
- To examine the relation between CUYP3A4 genotype and the pharmacokinetics of
the primary objective.
- To examine the relation between maternal age and the pharmacokinetics of the
primary objective.
- To examine the relation between fetal sex and the pharmacokinetics of the
primary objective.
- To examine the relation between maternal weight/BMI and the pharmacokinetics
of the primary objective.
- To examine the relation between the number of fetus and the pharmacokinetics
of the primary objective
- To examine the relation between parity the pharmacokinetics of the primary
objective.
- To examine the relation between pre-eclampsia and the pharmacokinetics of the
primary objective
- To examine the relation between oestradiol on pharmacokinetics of the primary
objective
- To examine the relation between pharmacokinetics in cord blood and neonatal
blood
Background 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 #6}, has long-term adverse consequences for
postnatal health {Huddy, 2001 #8} 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 #2;Roberts, 2017 #3;Travers, 2018 #1} 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 #4} 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 #5}, 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. As an example, synthetic
corticosteroids are eliminated by the liver by action of the enzyme cytochrome
P450 (CYP) 3A4 and variations of Single Nucleotide Polymorphisms (SNPs) in the
CYP3A4 gene will result in different drug effects and even adverse effects.
Study objective
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 for pregnant women suspected of preterm birth with a gestational age
between 23+5 until 33+6 weeks.
Study design
A clinical observational pilot study.
Study burden and risks
For all participants the extra burden will be the insertion of an intravenous
canule that will solely be used for blood sample collection. After each
administration of antenatal steroids, blood samples (1 ml, 1 EDTA tube) will be
collected in sampling time windows according to a schedule.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
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.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL71592.078.19 |
| Other | NL9318 |