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Study of Pharmacology of 17-OHPC in Pregnancy

Phase 2
Completed
Conditions
Pregnancy
Interventions
Drug: 17-OHPC
Procedure: Blood Draws
Registration Number
NCT00409825
Lead Sponsor
University of Pittsburgh
Brief Summary

We are examining the pharmacology of 17-OHPC in pregnancy, specifically between the second and third trimesters.

Detailed Description

The recently completed trial by the National Institute of Child Health and Human Development (NICHD)-sponsored Maternal-Fetal Medicine Units (MFMU) Network has demonstrated that intramuscular 17-alpha-hydroxyprogesterone caproate (17-OHPC) substantially reduces the rate of preterm birth in women at high risk for preterm delivery because of a prior spontaneous preterm birth. No other strategy or treatment for prevention of preterm birth has proven to be effective. Consequently, the American College of Obstetricians and Gynecologists has cautiously supported this treatment but points out that much more information about this therapy and alternative therapies is required. Although a large body of evidence exists about the safety of this treatment, almost nothing is known about the pharmacology of this agent, especially in pregnancy. The purpose of this study is to define the pharmacology of 17-hydroxyprogesterone caproate in pregnancy. This protocol will focus on pharmacokinetics and placental transport and provide preliminary data on the pharmacoepidemiology of 17-OHPC. The primary research question of this study is: Do the pharmacokinetics of 17-OHPC as represented by area under the concentration vs. time curve after IM injection of 250 mg 17-OHPC differ between the second and third trimesters of pregnancy? We will obtain blood samples prior to and daily for one week after injection of 17-OHPC (8 samples total) for each of two parts of the study, with an optional third part for eligible subjects. Additionally, blood samples will be collected prior to each weekly injection of the study drug and at time of delivery. Approximately 60 subjects (ages 18-45) will be accrued at one of the Obstetrical Fetal Pharmacology Research Units (OPRU) Network sites, with 15 at Magee-Womens Hospital of the University of Pittsburgh Medical Center. Study treatment will be administered until delivery. The total duration of this multi-center study is 2-3 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
61
Inclusion Criteria
  • Singleton gestation prior to 20 0/7 weeks gestation
  • Planning to receive or receiving 17-OHPC (250 mg IM weekly)
  • Previous history of preterm birth
  • Able to give consent
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Exclusion Criteria
  • Fetal demise, anomaly, or growth restriction
  • Hepatic or renal dysfunction
  • Placental previa or abruptio placenta
  • Polyhydramnios/oligohydramnios
  • Short cervix or planned cerclage
  • Chronic use of steroids, antiepileptics, antihypertensives, SSRS, street drugs
  • Participation in another interventional study that influences gestational age at delivery
  • Heparin treatment of known platelet count <100,000/mm3 (because of contraindication to intra-muscular injections)
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Part 1Blood DrawsPart 1 done after 4 weekly 17-OHPC injections completed, between 20 6/7 to 24 6/7 weeks gestation. 10 cc blood drawn pre-5th injection. 10 cc blood drawn 12 hours post-dose and 7 consecutive days. 24-hour urine collected days 4-5 within 7 days post-injection. Part 2 done 31 0/7 to 34 6/7 or at 35 0/7 weeks. 10 cc blood drawn pre weekly injection, 12 hours post-dose, and 7 consecutive days. 24-hour urine collected between days 4-5 within 7 days post-injection. A subject in whom Part 2 is performed during the last scheduled injection of 17-OHPC (at or around 35 0/7 weeks) will have the option to participate in Part 3, in which 10 cc of blood will be drawn serially over 21 days after completing Part 2. Blood will be drawn on days 9, 11, 14, 17, 20, 24, 28 after the last injection. Part 4: At the time of labor and delivery, subject will have 10cc of blood removed from a maternal peripheral vein. 10cc of blood will be collected from the placenta/umbilical cord after delivery.
Part 117-OHPCPart 1 done after 4 weekly 17-OHPC injections completed, between 20 6/7 to 24 6/7 weeks gestation. 10 cc blood drawn pre-5th injection. 10 cc blood drawn 12 hours post-dose and 7 consecutive days. 24-hour urine collected days 4-5 within 7 days post-injection. Part 2 done 31 0/7 to 34 6/7 or at 35 0/7 weeks. 10 cc blood drawn pre weekly injection, 12 hours post-dose, and 7 consecutive days. 24-hour urine collected between days 4-5 within 7 days post-injection. A subject in whom Part 2 is performed during the last scheduled injection of 17-OHPC (at or around 35 0/7 weeks) will have the option to participate in Part 3, in which 10 cc of blood will be drawn serially over 21 days after completing Part 2. Blood will be drawn on days 9, 11, 14, 17, 20, 24, 28 after the last injection. Part 4: At the time of labor and delivery, subject will have 10cc of blood removed from a maternal peripheral vein. 10cc of blood will be collected from the placenta/umbilical cord after delivery.
Primary Outcome Measures
NameTimeMethod
Change in the Area Under the Concentration vs. Time Curve in the Second and Third Trimesters of Pregnancy.Second and third trimesters of pregnancy

Change in the area under the concentration vs. time curve in the second and third trimesters of pregnancy.

We compared AUC at each PK study visit. Measurements were obtained at 0, 1, 2, 3, 4, 5, 6, 7 days.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (4)

University of Texas

🇺🇸

Galveston, Texas, United States

Magee-Womens Hospital of University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Georgetown University

🇺🇸

Washington, District of Columbia, United States

University of Washington

🇺🇸

Seattle, Washington, United States

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