Clinical trial NCT02793700: Pharmacokinetics (PK) and Modeling of Betamethasone Therapy in Threatened Preterm Birth
Official title: Pharmacokinetics and Modeling of Betamethasone Therapy in Threatened Preterm Birth
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Premature Labor
Keywords: Betamethasone
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2016-06-08
Enrollment: 210
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Women 18 years of age or older who are between 23-34 weeks gestation and being administered BMZ for fetal lung maturity.

Brief summary: Respiratory distress syndrome (RDS) is a life-threatening condition for premature neonates. Antenatal glucocorticoids have been used clinically in women with threatened preterm birth to accelerate lung maturation for more than 40 years. The current treatment strategy for women with threatened preterm delivery is for a standard, "one size fits all" dosing with either betamethasone (BMZ) or dexamethasone. It is well known that pregnancy introduces additional variability in response to medication therapy with different physiological changes and alterations in the activity of drug metabolizing enzymes. The objective of this project is to evaluate the pharmacokinetic (PK), pharmacodynamic, and pharmacogenetic parameters of betamethasone (BMZ) and determine the differences in response and benefit in pregnancy. An individualized dosing approach to medications in pregnancy, such as BMZ, is crucial to optimize efficacy of this important medication.

Detailed description: After consent, a maternal sample of whole blood will be obtained for DNA isolation. Investigators will collect plasma samples at 4 time points on all participants. These will be done at baseline (pre-dose), and 0.5-2 hours, 4-6 hours, and 22-24 hours after the first dose of BMZ is administered. Investigators will obtain serum for estriol measurement on all participants before or within 2 hours of antenatal corticosteroid administration and about 24 hours after each dose is given (betamethasone is administered as 2 doses 24 hours apart). Investigators will obtain a saliva sample for measurement of estriol at the same times. Participants will be offered optional participation in a more detailed PK portion of the study. Participants who consent to this part of the study will have additional plasma samples obtained at a schedule of sampling of approximately 10-15 hours after the first dose and then 6-8 hours, 24, and 48 hours after the 2nd dose. One sample will be collected at each of these times. At the time of delivery, umbilical cord blood will be collected before being discarded for DNA, serum and plasma. Four placenta sections will be collected. A maternal blood sample will also be obtained for serum and plasma. If the investigators are unable to obtain umbilical cord blood, a buccal swab will be collected from the baby for DNA extraction. A chart review will be done on the infant within 30 days of birth to review and record neonatal outcomes.

Eligibility criteria: Inclusion Criteria:

* Gestational age between 23-34 weeks with a diagnosis of threatened preterm labor or preterm premature rupture of membranes, or other diagnosis with a high likelihood of preterm delivery where the provider is recommending administering antenatal corticosteroids
* Singleton gestation
* Live fetus at the time of enrollment
* Being administered antenatal corticosteroids to enhance lung maturity
* Ability to provide written informed consent to participate in the study

Exclusion Criteria:

* Maternal age \<18 years old
* Major congenital anomalies
* Known severe abruptio placentae at the time of enrollment
* Multiple gestations
* Hepatic failure (history of hepatic failure, cirrhosis or 2- fold increase in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT)
* Renal failure (serum creatinine \> 2 mg/dl)

Primary outcomes:
measure: Diagnosis of respiratory distress syndrome
timeFrame: up to 30 days of life
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Eskenazi Hospital
state: Indiana
city: Indianapolis
country: United States
facility: IUH Methodist Hospital
state: Indiana
Study officials:
affiliation: Indiana University
name: David M Haas, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: