Relationship Between Plasma Concentration of Hydroxyprogesterone Caproate (17-OHPC) and Preterm Birth (PRO)

October 16, 2023 updated by: Steve N. Caritis, MD

Relationship Between Plasma Concentration of (Hydroxyprogesterone Caproate) 17-OHPC and Preterm Birth

The study plans to determine the relationship between plasma concentrations of 17-OHPC hydroxyprogesterone caproate (17-OHPC) and the rate of preterm birth. The study is an open label study of pregnant women with one or more prior spontaneous preterm births who are receiving either 250mg of 500 mg of 17-OHPC as a weekly single injection. The safety of the 500 mg dose will also be assessed.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study will determine the association between plasma concentrations of 17-OHPC (hydroxyprogesterone caproate) and the rate of preterm birth and will evaluate the impact of several potential covariates on plasma concentrations of 17-OHPC and its efficacy. 17-OHPC (hydroxyprogesterone caproate) administration has proven effective in reducing preterm births in high risk groups but the current dose of 250mg administered intramuscular (IM ) is thought to be an inadequate for a substantial portion of women receiving the therapy. The potential benefit of identifying a therapeutic concentration range and of optimizing the dosage of 17-OHPC are substantial.

One cohort of pregnant subjects with a history of a prior spontaneous preterm birth with be randomized to either the 250mg or 500mg weekly intramuscular injections. All subjects will have trough blood samples collected immediately prior to their second injection of the 17-OHPC, at 26-30 weeks (but only after a minimum of 7 injections have been administered) , 6-9 weeks later and at the time of delivery. Another tube of maternal blood will be collected during one of the scheduled blood samples for genotyping. A cord blood specimen will also be collected and with consent, a cord blood specimen will be collected for genetic studies of the infant. Investigators will also collect a small sample of the placenta after delivery.

In order to enhance sample size for this trial, investigators will also enroll a second cohort of subjects (ancillary cohort) who are not in the randomized clinical trial (RCT) described above. Women already receiving 250 mg 17-OHPC weekly from their healthcare provider as part of their standard of care will be approached prior to 26 weeks gestation. This will be an observational cohort and subjects enrolled in the ancillary cohort will not be randomized, as they are already receiving the 250 mg dose. Research staff will not administer the study drug to subjects enrolled in the ancillary cohort. These subjects will be asked to provide two blood samples: one at 26-30 weeks and one 6-9 weeks later, which will be utilized to address the primary objective of the study.

In response to the addition of the ancillary cohort, randomization for subjects in the RCT will be 2:1 for the 500 mg vs the 250 mg dose. The ancillary study will be implemented initially at the UPITT site only but may be expanded to other sites, as required.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
159

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh-Magee Womens Hospital
    • Texas
      • Galveston, Texas, United States, 77555
        • University of Texas Medical Branch
      • Houston, Texas, United States, 77030
        • University of Texas
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

  1. Randomized Clinical Trial Eligibility Criteria:

    Inclusion Criteria:

    • pregnant with a prior preterm birth 16 0/7-35 6/7 weeks from spontaneous labor or preterm premature rupture of membranes(PPROM),
    • current gestational age <22 weeks,
    • pregnant with one baby
    • age between 18-45 years
    • able to give consent and undergo study procedures

    Exclusion Criteria:

    • plans for cerclage at enrollment, plan for progesterone treatment other than study medications at enrollment
    • known fetal anomaly or chromosomal anomaly that could affect gestational age at delivery
    • malformation of the uterus or known cervical length <2.5cm
    • participation in another trial that may affect gestational age at delivery
    • planned delivery where outcome data cannot be collected
    • medical or obstetrical complication that may affect gestational age at delivery, such as active ulcerative colitis, liver tumors, liver disease/failure, renal disease/failure, undiagnosed vaginal bleeding unrelated to pregnancy, or hypertension requiring 2 or more agents
    • Current or history of thrombosis or thromboembolic disorders
    • known or suspected breast cancer, other hormone-sensitive cancer, or a history of these conditions
    • moderately severe depression (PHQ-9 score ≥ 15, EPDS score of >13, or suicidal ideation)
  2. Ancillary Cohort Eligibility Criteria:

Inclusion Criteria:

  • Pregnant female with documented prior birth between 16 0/7- 35 6/7 week gestation from spontaneous preterm labor or preterm premature rupture of membranes
  • Receiving 250 mg 17-OHPC weekly- must be compliant with that treatment based on interview and reviewing the medical record
  • Gestational age (GA) <26 weeks, based on study determined GA
  • Singleton gestation
  • Age between 18 - 45 years
  • Able to give informed consent and undergo study procedures

Exclusion Criteria:

  • Inclusion in the RCT of 250 vs 500 mg OPRC study
  • Cerclage in place
  • Plan for progesterone treatment other than study medication
  • Known major fetal anomaly or chromosomal anomalies that might affect gestational age at delivery
  • Malformation of uterus (uterine didelphus, septate uterus or bicornuate uterus) or known cervical length <2.5 cm
  • Participation in another trial that may affect gestational age at delivery
  • Planned delivery at other institution where pregnancy outcome data cannot be obtained
  • Medical or obstetrical complication that might affect gestational age at delivery, such as active ulcerative colitis, liver tumors, liver disease/failure, renal disease/failure, undiagnosed vaginal bleeding unrelated to pregnancy, or hypertension requiring 2 or more agents
  • Current or history of thrombosis or thromboembolic disorder.
  • Known or suspected breast cancer, other hormone-sensitive cancer, or a history of these conditions.
  • Moderately severe depression (PHQ-9 score ≥15, EPDS score of >13, or suicidal ideation)- based on criteria in the RCT

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: hydroxyprogesterone caproate 500 mg
For safety assessment of the 500 mg dose, subjects will be randomized to the 500 mg dose of 17-OHPC.
Drug: Safety study of 500 mg dose.
Subjects randomized to 250 mg or 500 mg dose
Other Names:
  • safety
Active Comparator: hydroxyprogesterone caproate 250 mg
For safety assessment of the 500 mg dose, subjects will be randomized to the 250mg dose of 17-OHPC.
Drug: 17-Hydroxyprogesterone caproate 250mg or 500 mg.
For the pharmacodynamic study, subjects receiving either 250mg or 500 mg dose will be studied to relate the plasma concentration at 26-30 to the rate of sPTB. For the safety study, subjects will be randomized to either the 250mg or 500 mg dose.
Other Names:
  • pharmacodynamic
Active Comparator: Ancillary cohort 250 mg dose
Receiving 250 mg as part of routine care
Drug: 17-Hydroxyprogesterone caproate 250mg or 500 mg.
For the pharmacodynamic study, subjects receiving either 250mg or 500 mg dose will be studied to relate the plasma concentration at 26-30 to the rate of sPTB. For the safety study, subjects will be randomized to either the 250mg or 500 mg dose.
Other Names:
  • pharmacodynamic

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Relationship Between 17-OHPC Concentration and Spontaneous Preterm Birth - A Concentration-Response Analysis
Time Frame: 26-30 week blood sample after a minimum of 7 injections among those with a blood sample and compliant with protocol(n=116)
relationship between the rate of spontaneous preterm birth ( delivery < 37 weeks) and drug concentration obtained at 26-30 weeks among those with a blood sample and adherent to study protocol (n=116)
26-30 week blood sample after a minimum of 7 injections among those with a blood sample and compliant with protocol(n=116)
Survival A
Time Frame: time in days from first injection to spontaneous preterm delivery
days from first injection to spontaneous preterm delivery
time in days from first injection to spontaneous preterm delivery
Survival B
Time Frame: days from blood sample time to spontaneous preterm delivery
days from when the 26-30 week blood sample was obtained to the gestation at spontaneous preterm birth. All blood samples were obtained after at least 7 injections were give by which time steady state would have been achieved. This analysis was limited to those with a 26-30 week blood sample who were compliant with the protocol
days from blood sample time to spontaneous preterm delivery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Composite Neonatal Outcome
Time Frame: till discharge from nicu up to 30 days
Composite NN outcome (fetal death, neonatal death (NND), respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage 3 or 4, retinopathy of prematurity, hypoxic-ischemic encephalopathy, seizures.) and NICU admission
till discharge from nicu up to 30 days
NICU Admission
Time Frame: any admission to the NICU from time of delivery to time of discharge from the hospital up to 30 days or transfer to another facility
Infants admitted to the NICU
any admission to the NICU from time of delivery to time of discharge from the hospital up to 30 days or transfer to another facility
Comparison of Plasma Concentration of 17-OHPC According to Dose
Time Frame: Blood sample obtained at 26-30 weeks after a minimum of 7 injections and compliant with study protocol

Plasma concentrations of 17-OHPC after 250 or 500 mg dose. Subjects were compliant with protocol up to the 26-30 week blood draw and had a blood sample available . This included subjects with indicated preterm birth and was not limited to those with spontaneous PTB. Plasma concentration among those receiving the 250 mg dose are compared to those receiving 500 mg dose.

Those receiving the 250 mg dose include both the RCT and ancillary groups.
Blood sample obtained at 26-30 weeks after a minimum of 7 injections and compliant with study protocol
Preterm Birth by Dosing Group
Time Frame: from enrollment till preterm delivery
rate of preterm birth according to dosing group. Subjects were the same cohort in spec aims 1 and 2 . They were compliant with protocol, had a 26-30 week blood sample and did not miss more than 2 injections.
from enrollment till preterm delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Steve N. Caritis, MD

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Steve N Caritis, MD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 12, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 2, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 2, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 26, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 23, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO16110007
  • U54HD047905-11 (U.S. NIH Grant/Contract)
  • STUDY19020368 (Other Identifier: PittPRO)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified data to be shared include plasma 17-OHPC concentrations , rates of sPTB, and data on maternal adverse effects and neonatal outcomes

IPD Sharing Time Frame

These data will be eligible to the recruiting centers after the main data are published. they will have 18 months to request secondary analyses . other researchers will have access to the data after that period.

IPD Sharing Access Criteria

To be determined by the OPRC steering committee.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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