Pharmacokinetics (PK) and Modeling of Betamethasone Therapy in Threatened Preterm Birth

Premature Labor Clinical Trial

Official title:

Pharmacokinetics and Modeling of Betamethasone Therapy in Threatened Preterm Birth

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02793700
• Other study ID #: 1604640151
• Status: Completed
• Start date: July 2016
• Est. completion date: March 2022

Study information

• Verified date: March 2022
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: March 2022
• Est. primary completion date: March 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Obstetric Labor, Premature
• Premature Birth
• Premature Labor

Locations

Country	Name	City	State
United States	Eskenazi Hospital	Indianapolis	Indiana
United States	IUH Methodist Hospital	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnosis of respiratory distress syndrome	The diagnosis of RDS made by the neonatologist staff based on clinical criteria	up to 30 days of life