Clinical trial NCT03433040: 17OHP-C Dosing Among Obese Pregnant Women
Official title: Impact of a Higher Dose on the Pharmacokinetics of 17-alpha Hydroxyprogesterone Caproate in Obese Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Premature Birth
Absorption; Chemicals
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: Washington University School of Medicine
First posted: 2018-02-14
Enrollment: 44
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Mean Trough Levels of 17-OHPC in the Three Groups at 20-22 Weeks, 27-29 Weeks and 34-36 Weeks.
timeFrame: From enrollment to 36 weeks of pregnancy
Secondary outcomes:
measure: Gestational Age at Delivery
timeFrame: Up to 37 weeks
Other outcomes:
Locations:
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
Study officials:
affiliation: University of South Florida
name: Anthony O Odibo, MD
role: PRINCIPAL_INVESTIGATOR
References: