Pregnancy
Conditions
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.
Interventions
DRUG17-OHPC
Intra-muscular injection of 250 mg 17-OHPC administered weekly between the second and third trimesters of pregnancy, until time of delivery.
PROCEDUREBlood Draws
10 cc of blood will be drawn prior to the fifth weekly administration of 17-OHPC during second trimester of pregnancy, and then once daily for seven consecutive days post-dose. 10 cc of blood also will be drawn prior to weekly administration of 17-OHPC from sixth weekly dose in the second trimester until the last scheduled dose in the third trimester. Prior to this last scheduled dose, 10 cc of blood will be drawn, as well as once daily for seven consecutive days post-dose.
Sponsors
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AUC1 vs AUC2 AUC 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.
AUC 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. | 61 |
| Total | 61 |
Baseline characteristics
| Characteristic | AUC1 vs AUC2 |
|---|---|
| Age, Continuous | 28.01 years STANDARD_DEVIATION 5.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 61 participants |
| Sex: Female, Male Female | 61 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 61 |
| serious Total, serious adverse events | 0 / 61 |
Outcome results
Primary
Change in the Area Under the Concentration vs. Time Curve in the 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.
Time frame: Second and third trimesters of pregnancy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 | Change in the Area Under the Concentration vs. Time Curve in the Second and Third Trimesters of Pregnancy. | AUC -1 | 115 ng/ML/day | Standard Deviation 44 |
| Part 1 | Change in the Area Under the Concentration vs. Time Curve in the Second and Third Trimesters of Pregnancy. | AUC - 2 | 136 ng/ML/day | Standard Deviation 52 |