Indomethacin PK and PD Therapy in Pregnancy

NCT02451228 | Completed DMC FDA Drug

• 2 other identifiers: 15-00671R01HD083003-01
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 6

Brief Summary

This study will follow pregnant women who are taking indomethacin as Standard of Care (SOC) for the indications of preterm labor (PTL), short cervix, or other indications, to evaluate the pharmacokinetics (PK), what the body does to the drug, and pharmacodynamics (PD), effectiveness of the drug in treating the specific intended disease process of this medication. This will help us develop more information for medication dosing specific to pregnant women experiencing preterm labor. Indomethacin is often prescribed to pregnant women presenting with preterm labor or shortened cervix, which places them at risk for preterm labor and delivery. Indomethacin has been used since the 1970s to prolong pregnancy by decreasing uterine contractions. However, despite the widespread use of indomethacin in pregnancy, there is limited information available to help physicians determine how much indomethacin to prescribe and how often to prescribe it.

Conditions

Premature Labor; Pregnancy; Premature Birth

Keywords

Pharmacokinetics; Pharmacodynamics; Preterm labor; Preterm birth; Estradiol; Indomethacin; Pregnancy; Short Cervix; CYP2C9 Genotype

Outcome Measures

Primary Outcomes (1)

• Gestational age at delivery

  Gestational age at delivery calculated from the first day of last menstrual period unless "unsure" and then it will be calculated from ultrasound measurements

  Enrollment until delivery of the participant

Secondary Outcomes (4)

• Maternal outcomes

  Enrollment until delivery and maternal discharge

• Neonatal outcomes

  The earlier of neonatal discharge or up to 120 days postnatal

• Neonatal admission to Neonatal intensive care unit (NICU)

  The earlier of neonatal discharge or up to 120 days postnatal

• Length of stay in the Neonatal intensive care unit (NICU)

  The earlier of neonatal discharge or up to 120 days postnatal

Study Arms (1)

Single-group

Observational opportunistic pharmacokinetic study of 300 pregnant women receiving Indomethacin therapy as standard of care for risk of preterm birth. Receive serial blood collection from IV.

Other: Serial blood collection

Interventions

Serial blood collection OTHER

Serial blood collection from IV for pharmacokinetic and pharmacodynamic analysis. No drug, device, or biologic intervention. Opportunistic.

Single-group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a multi-center study including 300 pregnant women between 12-32 weeks of gestation at risk of PTB (sPTL or shortened cervix with or without funneling membranes) or other conditions to whom indomethacin is prescribed.

You may qualify if:

• To be enrolled in the study, patients must meet all of the following criteria:
• Age at least 18 years
• Singleton gestation
• /7 to 32 0/7 weeks gestation (see Gestational Age Determination section 3.2.1.1)
• Patient receiving indomethacin for any of the following diagnoses:
• Preterm labor: regular uterine contractions with documented cervical change or dilatation ≥ 2 cm and 80% effacement
• Cervical shortening (\< 2.5 cm documented on transvaginal ultrasound) with or without funneling membranes
• Planned cervical cerclage or emergent cerclage
• Other condition whereby Indomethacin is indicated
• Maternal and fetal condition allows anticipated delay of delivery for more than 24 hours -

You may not qualify if:

• Contraindications to indomethacin use (history of maternal bleeding disorder, thrombocytopenia, maternal hepatic, gastrointestinal ulcerative, or renal dysfunction, asthma)
• Known fetal abnormality, genetic syndrome, or intrauterine fetal demise
• Anticipated delivery in less than 24 hours, cervical dilatation \> 6 cm
• Preterm premature rupture of membranes
• Suspected chorioamnionitis
• Oligohydramnios (DVP \< 2 cm)
• Congenital Uterine anomaly
• Vaginal bleeding due to suspected placental abruption or placenta previa
• Planned preterm delivery for maternal/fetal indications
• Non-reassuring fetal status
• Planned delivery outside UTMB or participation in another intervention trial which may affect maternal or neonatal outcomes
• Unsure gestational age due to possibility of intrauterine growth restriction
• Hematocrit \<28% (as determined by most recent result within 1 month of enrollment)
• Prisoners

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (6)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

University of Texas Medical Branch, Dept of OB/GYN

Galveston, Texas, 77555-0587, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Maternal Venous Blood for serum Maternal Blood for DNA (for CYP2C9) Maternal Urine Cord Blood (Umbilical Vein and Artery) for serum

MeSH Terms

Conditions

Obstetric Labor, Premature; Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Gary Hankins, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

• Erik Rytting, PhD

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: May 21, 2015
• Study Start: May 1, 2015
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: June 11, 2019

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)