Preterm BirthPhase 1/2PRONCT03292731
Relationship Between Plasma Concentration of Hydroxyprogesterone Caproate (17-OHPC) and Preterm Birth
A Phase 1/2 study testing 17-Hydroxyprogesterone caproate 250mg or 500 mg. and Safety study of 500 mg dose. in people with Preterm Birth, run by Steve N. Caritis, MD at 5 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preterm Birth
- What is being tested?
- 17-Hydroxyprogesterone caproate 250mg or 500 mg. and Safety study of 500 mg dose.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 159 participants
- Where
- 5 sitesUnited States
- Study dates
- 12 Feb 2018to 2 Sep 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- 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
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- 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
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
- Ancillary Cohort Eligibility Criteria:
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Northwestern University
Chicago, Illinois, 60611
University of Texas Medical Branch
Galveston, Texas, 77555
University of Texas
Houston, Texas, 77030
University of Pittsburgh-Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
University of Utah
Salt Lake City, Utah, 84132
About this study
Official title: 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.
Read the 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.
- Conditions
- Preterm Birth
- Being tested
- 17-Hydroxyprogesterone caproate 250mg or 500 mg., Safety study of 500 mg dose.
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
17-Hydroxyprogesterone caproate 250mg or 500 mg.Drug
Also called pharmacodynamic
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.
Safety study of 500 mg dose.Drug
Also called safety
Subjects randomized to 250 mg or 500 mg dose
| Study group | Role | What they receive |
|---|---|---|
| hydroxyprogesterone caproate 500 mg | Experimental | For safety assessment of the 500 mg dose, subjects will be randomized to the 500 mg dose of 17-OHPC. Receives: Drug: Safety study of 500 mg dose. |
| hydroxyprogesterone caproate 250 mg | Active comparator | For safety assessment of the 500 mg dose, subjects will be randomized to the 250mg dose of 17-OHPC. Receives: Drug: 17-Hydroxyprogesterone caproate 250mg or 500 mg. |
| Ancillary cohort 250 mg dose | Active comparator | Receiving 250 mg as part of routine care Receives: Drug: 17-Hydroxyprogesterone caproate 250mg or 500 mg. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relationship Between 17-OHPC Concentration and Spontaneous Preterm Birth - A Concentration-Response Analysis
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)
Measured: 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
days from first injection to spontaneous preterm delivery
Measured: time in days from first injection to spontaneous preterm delivery
Survival B
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
Measured: days from blood sample time to spontaneous preterm delivery
Secondary outcomes (4)
Composite Neonatal Outcome
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
Measured: till discharge from nicu up to 30 days
NICU Admission
Infants admitted to the NICU
Measured: 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
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.
Measured: Blood sample obtained at 26-30 weeks after a minimum of 7 injections and compliant with study protocol
Preterm Birth by Dosing Group
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.
Measured: from enrollment till preterm delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2017
- Study start12 Feb 2018
- Primary completion2 Sep 2021
- Study completion2 Sep 2021
Why it stopped: grant funding cycle ended
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An open labelled rct for secondary analysis of safety of 500 mg dose. A pharmacodynamic study of 17-OHPC concentration and rate of sPTB
- Masking
- None (open label)
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steve N. Caritis, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Steve N. Caritis, MD, University of Pittsburgh
- Investigators
- Steve N Caritis, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03292731
- Sponsor's protocol ID
- PRO16110007
- Other IDs
- U54HD047905-11, STUDY19020368
- Acronym
- PRO
- Status last verified
- Oct 2023
- First submitted
- 20 Sep 2017
- Last updated
- 23 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified data to be shared include plasma 17-OHPC concentrations , rates of sPTB, and data on maternal adverse effects and neonatal outcomes
Publications
Caritis SN, Costantine MM, Clark S, Stika CS, Kiley JW, Metz TD, Chauhan SP, Venkataramanan R; Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Centers Network. Relationship between plasma concentration of 17-hydroxyprogesterone caproate and gestational age at preterm delivery. Am J Obstet Gynecol MFM. 2023 Jul;5(7):100980. doi: 10.1016/j.ajogmf.2023.100980. Epub 2023 Apr 24.
PubMed 37100349
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relationship Between Plasma Concentration of (Hydroxyprogesterone Caproate) 17-OHPC and Preterm Birth
- ClinicalTrials.gov ID
- NCT03292731
- Acronym / sponsor ID
- PRO / PRO16110007
- Conditions
- Preterm Birth
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: grant funding cycle ended
- Enrolment
- 159 participants (actual)
- Lead sponsor
- Steve N. Caritis, MDUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 12 Feb 2018 (actual)
- Primary completion
- 2 Sep 2021 (actual)
- Study completion
- 2 Sep 2021 (actual)
- First posted
- 26 Sep 2017 (actual)
- Results
- Posted 23 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- An open labelled rct for secondary analysis of safety of 500 mg dose. A pharmacodynamic study of 17-OHPC concentration and rate of sPTB
| Arm | Type | Receives |
|---|---|---|
| hydroxyprogesterone caproate 500 mg | Experimental | Drug: Safety study of 500 mg dose.For safety assessment of the 500 mg dose, subjects will be randomized to the 500 mg dose of 17-OHPC. |
| hydroxyprogesterone caproate 250 mg | Active comparator | Drug: 17-Hydroxyprogesterone caproate 250mg or 500 mg.For safety assessment of the 500 mg dose, subjects will be randomized to the 250mg dose of 17-OHPC. |
| Ancillary cohort 250 mg dose | Active comparator | Drug: 17-Hydroxyprogesterone caproate 250mg or 500 mg.Receiving 250 mg as part of routine care |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (10 listed)
- Ancillary Cohort Eligibility Criteria:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 17-Hydroxyprogesterone caproate 250mg or 500 mg.Also: pharmacodynamicFor 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. | Drug | Ancillary cohort 250 mg dose, hydroxyprogesterone caproate 250 mg |
| Safety study of 500 mg dose.Also: safetySubjects randomized to 250 mg or 500 mg dose | Drug | hydroxyprogesterone caproate 500 mg |
Primary outcome
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)
Survival A
Time frame: time in days from first injection to spontaneous preterm delivery
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
4 secondary outcomes
Composite Neonatal Outcome
Time frame: 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
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
Preterm Birth by Dosing Group
Time frame: from enrollment till preterm delivery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37100349Caritis SN, Costantine MM, Clark S, Stika CS, Kiley JW, Metz TD, Chauhan SP, Venkataramanan R; Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Centers Network. Relationship between plasma concentration of 17-hydroxyprogesterone caproate and gestational age at preterm delivery. Am J Obstet Gynecol MFM. 2023 Jul;5(7):100980. doi: 10.1016/j.ajogmf.2023.100980. Epub 2023 Apr 24.
- Individual participant dataSharing planned: Yes. Deidentified data to be shared include plasma 17-OHPC concentrations , rates of sPTB, and data on maternal adverse effects and neonatal outcomes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steve N Caritis, MD principal investigator
University of Pittsburgh
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 17-Hydroxyprogesterone caproate 250mg or 500 mg. and Safety study of 500 mg dose. in people with Preterm Birth, run by Steve N. Caritis, MD at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03292731, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.