Premature LaborNCT02451228
Indomethacin PK and PD Therapy in Pregnancy
An observational study of Premature Labor and Pregnancy, run by The University of Texas Medical Branch, Galveston at 6 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Premature Labor, Pregnancy, Premature Birth
- What is being tested?
- Serial blood collection
- Type of treatment
- Injection or infusion
- How many people
- 62 participants
- Where
- 6 sitesUnited States
- Study dates
- May 2015to 31 Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- To be enrolled in the study, patients must meet all of the following criteria:
- Age at least 18 years
- Singleton gestation
- 12 0/7 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
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- 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 -
Who cannot join
- 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)
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- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Alabama
Birmingham, Alabama, 35233
Duke University
Durham, North Carolina, 27705
University of Texas Medical Branch, Dept of OB/GYN
Galveston, Texas, 77555-0587
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Columbia University
New York, New York, 10032
University of Utah
Salt Lake City, Utah, 84132
About this study
Official title: Pharmacokinetic and Pharmacogenomic Approach to Indomethacin Therapy in Pregnancy
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.
Read the detailed description
Opportunistic study of indomethacin prescribed to patients per standard of care. Determine the pharmacokinetics, pharmacodynamics and pharmacogenomics of Indomethacin in pregnant patients with the hypothesis that that estradiol levels during pregnancy (12-32 weeks of gestation) and CYP2C9 polymorphisms affect the PK of indomethacin, and subsequently, the response to indomethacin therapy in patients at risk of Preterm birth (PTB). This hypothesis will be tested with the following specific aims: (1) Determine the PK of indomethacin in pregnant women at risk of PTB and its PD effects on reducing the rate of PTB before 34 weeks of gestation, as well as any associations between the PK and secondary maternal/neonatal clinical outcomes; (2) Determine the effects of maternal levels of estradiol in mid-pregnancy and CYP2C9 polymorphisms on indomethacin biotransformation to O-desmethylindomethacin in pregnant patients; (3) Construct a population PK/PD model of indomethacin in patients at risk of PTB (12-32 weeks of gestation) in order to optimize the dose and the dosing frequency for indomethacin prescribed to each individual based on covariates such as race/ethnicity, CYP2C9 genotype, gestational age, estradiol levels, smoking status, and body mass index (BMI). The investigators will enroll 300 subjects with spontaneous preterm labor (sPTL) or shortened cervix in a prospective opportunistic PK study designed to correlate the PK of indomethacin, patient genotype, and clinical outcomes. The investigators will merge dosing, sampling, demographic, and clinical information with the drug concentration data and use population PK methodologies to analyze the data using nonlinear mixed effect modeling. Quantification of the differences within and between individuals allows for identification of covariates (e.g., CYP2C9 genotype, estradiol levels, BMI, etc.) that can explain variability and affect drug exposure. These covariates, if significant, can then be used in the future to optimize dosing in individual patients at risk for PTB. Achieving this goal of individualized indomethacin therapy could have a significant impact on clinical practice and improve maternal and neonatal outcomes.
- Conditions
- Premature Labor, Pregnancy, Premature Birth
- Being tested
- Serial blood collection
- Keywords
- Pharmacokinetics, Pharmacodynamics, Preterm labor, Preterm birth, Estradiol, Indomethacin, Pregnancy, Short Cervix, CYP2C9 Genotype
- Medical subject headings
- Obstetric Labor, Premature, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serial blood collectionOther
Serial blood collection from IV for pharmacokinetic and pharmacodynamic analysis. No drug, device, or biologic intervention. Opportunistic.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Serial blood collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Enrollment until delivery of the participant
Secondary outcomes (4)
Maternal outcomes
Diagnosed maternal outcomes including oligohydramnios, chorioamnionitis, preterm premature rupture of membranes, venous thromboembolism, pulmonary edema, postpartum hemorrhage, and maternal death
Measured: Enrollment until delivery and maternal discharge
Neonatal outcomes
Diagnosed neonatal outcomes including birth weight, APGAR scores, neonatal sepsis, respiratory distress syndrome, patent ductus arteriosis, necrotizing enterocolitis, broncopulmonary dysplasia, paraventricular leukomalacia, intraventricular hemorrhage, fetal, or neonatal death
Measured: The earlier of neonatal discharge or up to 120 days postnatal
Neonatal admission to Neonatal intensive care unit (NICU)
Documentation of NICU admission [yes/no]
Measured: The earlier of neonatal discharge or up to 120 days postnatal
Length of stay in the Neonatal intensive care unit (NICU)
If admitted to the NICU, number of days in the NICU
Measured: The earlier of neonatal discharge or up to 120 days postnatal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2015 (estimated)
- Study startMay 2015
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature LaborStudies of the same condition, open and under way.
- More trials run by The University of Texas Medical Branch, GalvestonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Gary Hankins, MD, Principal investigator, University of TexasErik Rytting, PhD, Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02451228
- Sponsor's protocol ID
- 15-0067
- Other IDs
- 1R01HD083003-01
- Status last verified
- Feb 2018
- First submitted
- 19 May 2015
- Last updated
- 11 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Once published
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic and Pharmacogenomic Approach to Indomethacin Therapy in Pregnancy
- ClinicalTrials.gov ID
- NCT02451228
- Acronym / sponsor ID
- 15-0067
- Conditions
- Premature Labor, Pregnancy, Premature Birth
- Keywords
- Pharmacokinetics, Pharmacodynamics, Preterm labor, Preterm birth, Estradiol, Indomethacin, Pregnancy, Short Cervix
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- The University of Texas Medical Branch, GalvestonUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- May 2015
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 21 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Opportunistic study of indomethacin prescribed to patients per standard of care. Determine the pharmacokinetics, pharmacodynamics and pharmacogenomics of Indomethacin in pregnant patients with the hypothesis that that estradiol levels during pregnancy (12-32 weeks of gestation) and CYP2C9 polymorphisms affect the PK of indomethacin, and subsequently, the response to indomethacin therapy in patients at risk of Preterm birth (PTB). This hypothesis will be tested with the following specific aims: (1) Determine the PK of indomethacin in pregnant women at risk of PTB and its PD effects on reducing the rate of PTB before 34 weeks of gestation, as well as any associations between the PK and secondary maternal/neonatal clinical outcomes; (2) Determine the effects of maternal levels of estradiol in mid-pregnancy and CYP2C9 polymorphisms on indomethacin biotransformation to O-desmethylindomethacin in pregnant patients; (3) Construct a population PK/PD model of indomethacin in patients at risk of PTB (12-32 weeks of gestation) in order to optimize the dose and the dosing frequency for indomethacin prescribed to each individual based on covariates such as race/ethnicity, CYP2C9 genotype, gestational age, estradiol levels, smoking status, and body mass index (BMI). The investigators will enroll 300 subjects with spontaneous preterm labor (sPTL) or shortened cervix in a prospective opportunistic PK study designed to correlate the PK of indomethacin, patient genotype, and clinical outcomes. The investigators will merge dosing, sampling, demographic, and clinical information with the drug concentration data and use population PK methodologies to analyze the data using nonlinear mixed effect modeling. Quantification of the differences within and between individuals allows for identification of covariates (e.g., CYP2C9 genotype, estradiol levels, BMI, etc.) that can explain variability and affect drug exposure. These covariates, if significant, can then be used in the future to optimize dosing in individual patients at risk for PTB. Achieving this goal of individualized indomethacin therapy could have a significant impact on clinical practice and improve maternal and neonatal outcomes.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single-group | – | Other: Serial blood collectionObservational 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- Age at least 18 years
- Singleton gestation
- 12 0/7 to 32 0/7 weeks gestation (see Gestational Age Determination section 3.2.1.1)
- Patient receiving indomethacin for any of the following diagnoses:
- Maternal and fetal condition allows anticipated delay of delivery for more than 24 hours -
Key exclusion criteria (14 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Serial blood collectionSerial blood collection from IV for pharmacokinetic and pharmacodynamic analysis. No drug, device, or biologic intervention. Opportunistic. | Other | Single-group |
Primary outcome
Gestational age at delivery
Time frame: Enrollment until delivery of the participant
Gestational age at delivery calculated from the first day of last menstrual period unless "unsure" and then it will be calculated from ultrasound measurements
4 secondary outcomes
Maternal outcomes
Time frame: Enrollment until delivery and maternal discharge
Neonatal outcomes
Time frame: The earlier of neonatal discharge or up to 120 days postnatal
Neonatal admission to Neonatal intensive care unit (NICU)
Time frame: The earlier of neonatal discharge or up to 120 days postnatal
Length of stay in the Neonatal intensive care unit (NICU)
Time frame: The earlier of neonatal discharge or up to 120 days postnatal
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2019.
- Individual participant dataSharing planned: No. Once published
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Hankins, MD principal investigator
University of Texas
Erik Rytting, PhD principal investigator
University of Texas
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Premature Labor and Pregnancy, run by The University of Texas Medical Branch, Galveston at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gestational age at delivery (time frame: Enrollment until delivery of the participant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2019.