Absorption; Chemicals, Premature Birth
Conditions
Brief summary
Emergency data suggest 17OHP-C may be less efficacious in obese women. Since obesity is associated with lower levels of plasma 17OHP-C, the investigator hypothesize that higher doses of 17OHP-C may help to prevent spontaneous PTB among obese women. The study aims to compare the pharmacokinetics of 17 OHP-C in obese compared with non-obese women.
Detailed description
Prospective three arm study of women with a prior spontaneous PTB. Non-obese women will receive the standard 250 mg weekly dose of 17 OHP-C while obese women will be randomly assigned to the standard (250 mg) or higher dose (500 mg). The resulting three groups will consist of: 1. Normal weight women on 250mg 17OHPC 2. Obese women on 250mg 17OHPC 3. Obese women on 500mg of 17OHPC Initial Enrollment: Pregnant patients receiving prenatal care at one of the USF affiliated sites or Washington University in St. Louis sites who report a history of a PTB will be approached by the research nurse. The research nurse will explain the study, review inclusion/exclusion criteria with the patient, and invite interested potential study candidates to sign a medical records release so that records from the previous PTB can be reviewed. If the medical records confirm the birth of a previous PTB was of a live born singleton gestation between the gestational ages of 20 weeks and 36 weeks and 6 days then the patient will be invited to participate in the study. At that time the informed consent form will be thoroughly reviewed with the patient, and if the patient desires to enroll, the patient will provide informed consent to enroll in the study. Consecutive women with normal BMI or obese women meeting the inclusion criteria will be approached to avoid selection bias. Randomization: will occur at the time of enrollment. The randomization will be computer generated. Randomization envelopes indicating the randomization arm will be prepared ahead of time and the next consecutive envelope will be used at time of enrollment. Pharmacokinetic studies: Sampling schedule in order to investigate the pharmacokinetics of 250 mg 17OHP-C weekly as compared to 500 mg 17OHP-C weekly in obese women as well as 250 mg in non-obese women will be performed as follows: \- Using principles described by Caritis et al., four completed weeks of 17OHP-C therapy is required prior to sampling anticipating that steady state will be achieved by this time point.
Interventions
DRUG17-Hydroxyprogesterone Capronate
17-Hydroxyprogesterone Capronate 250mg versus 500mg
Sponsors
Washington University School of Medicine
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* \- Pregnant women, with a singleton gestation * Ages 18 - 55 * Able to read and write in English and / or Spanish * History of spontaneous PTB * Obesity (≥ 30 kg / m2 ) vs non-obese groups (18 - 29.9 kg / m2 ) defined by first documented body mass index at an office visit * Gestational age between 12 weeks, 0 days and 24 weeks, 6 days of gestation * An ultrasound before 24 + 6 weeks gestation to confirm dating and to rule out major fetal anomalies * Willing to have weekly injections at the physician's office * The newborn will be enrolled on the mothers consent for chart review only https://register.clinicaltrials.gov/prs/html/definitions.html?popup=true#Eligibility
Exclusion criteria
* \- Multifetal gestation * Known fetal anomaly * Current progesterone treatment * Known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions * Current or history of thrombosis or thromboembolic disorder * Current anticoagulation * Undiagnosed abnormal vaginal bleeding unrelated to pregnancy * Cholestatic jaundice of pregnancy * Liver tumors, benign or malignant, or active liver disease * uncontrolled hypertension (controlled hypertension is eligible) * A seizure disorder * Current or planned cervical cerclage * Plan to deliver elsewhere
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | From enrollment to 36 weeks of pregnancy | Blood levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gestational Age at Delivery | Up to 37 weeks | Gestational age at delivery in weeks . Too few to dichotomize to \<37, 34 and 32 weeks as previously planned. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non Obese 250mg 17 OHP-C
17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg | 17 |
| Obese - Control 250mg 17 OHP-C
17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg | 8 |
| Obese 500mg 17 OHP-C
17-Hydroxyprogesterone Capronate: 17-Hydroxyprogesterone Capronate 250mg versus 500mg | 5 |
| Total | 30 |
Baseline characteristics
| Characteristic | Obese - Control | Obese | Total | Non Obese |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 5 Participants | 30 Participants | 17 Participants |
| Age, Continuous | 31.6 years STANDARD_DEVIATION 6.4 | 31.4 years STANDARD_DEVIATION 4.6 | 31.7 years STANDARD_DEVIATION 5.2 | 32.2 years STANDARD_DEVIATION 5.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 1 Participants | 14 Participants | 9 Participants |
| Region of Enrollment United States | 8 Participants | 5 Participants | 30 Participants | 17 Participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 30 Participants | 17 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 8 | 0 / 5 |
| other Total, other adverse events | 0 / 17 | 0 / 8 | 0 / 5 |
| serious Total, serious adverse events | 0 / 17 | 0 / 8 | 0 / 5 |
Outcome results
Primary
Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks.
Blood levels
Time frame: From enrollment to 36 weeks of pregnancy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non Obese | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 34-36 weeks | 15.2 ng/ml | Standard Deviation 12.5 |
| Non Obese | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 27-29 weeks | 11.5 ng/ml | Standard Deviation 4.8 |
| Non Obese | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 20-22 weeks | 10.1 ng/ml | Standard Deviation 4.5 |
| Obese - Control | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 34-36 weeks | 11.1 ng/ml | Standard Deviation 6.2 |
| Obese - Control | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 20-22 weeks | 13.0 ng/ml | Standard Deviation 5.1 |
| Obese - Control | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 27-29 weeks | 8.1 ng/ml | Standard Deviation 5.6 |
| Obese | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 27-29 weeks | 17.9 ng/ml | Standard Deviation 2.5 |
| Obese | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 20-22 weeks | 18.0 ng/ml | Standard Deviation 6.7 |
| Obese | Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks. | 34-36 weeks | 24.6 ng/ml | Standard Deviation 7.1 |
Secondary
Gestational Age at Delivery
Gestational age at delivery in weeks . Too few to dichotomize to \<37, 34 and 32 weeks as previously planned.
Time frame: Up to 37 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Non Obese | Gestational Age at Delivery | 36.7 Weeks | Standard Deviation 2.6 |
| Obese - Control | Gestational Age at Delivery | 38.4 Weeks | Standard Deviation 1.4 |
| Obese | Gestational Age at Delivery | 32.2 Weeks | Standard Deviation 5.5 |