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

NCT03292731 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: PRO16110007U54HD047905-11STUDY19020368
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 5

Brief 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 weekly single injection. The safety of the 500 mg dose will also be assessed.

Conditions

Preterm Birth

Outcome Measures

Primary Outcomes (3)

• 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)

  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

  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

  days from blood sample time to spontaneous preterm delivery

Secondary Outcomes (4)

• Composite Neonatal Outcome

  till discharge from nicu up to 30 days

• NICU Admission

  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

  Blood sample obtained at 26-30 weeks after a minimum of 7 injections and compliant with study protocol

• Preterm Birth by Dosing Group

  from enrollment till preterm delivery

Study Arms (3)

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.

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.

Drug: 17-Hydroxyprogesterone caproate 250mg or 500 mg.

Ancillary cohort 250 mg dose

ACTIVE COMPARATOR

Receiving 250 mg as part of routine care

Drug: 17-Hydroxyprogesterone caproate 250mg or 500 mg.

Interventions

17-Hydroxyprogesterone caproate 250mg or 500 mg. DRUG

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.

Also known as: pharmacodynamic

Ancillary cohort 250 mg dose; hydroxyprogesterone caproate 250 mg

Safety study of 500 mg dose. DRUG

Subjects randomized to 250 mg or 500 mg dose

Also known as: safety

hydroxyprogesterone caproate 500 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Study of pregnant participants
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• Ancillary Cohort Eligibility 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

Sponsors & Collaborators

• Steve N. Caritis, MD: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Pittsburgh-Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

University of Texas

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• 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.

  PMID: 37100349 DERIVED

MeSH Terms

Conditions

Premature Birth

Interventions

Safety

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Accident Prevention; Accidents; Public Health; Environment and Public Health

Limitations and Caveats

Statistical analysis limited due to inadequate enrollment and subsequent small sample size and few cases of sPTB.

Results Point of Contact

• Title: steve caritis
• Organization: University of Pittsburgh

scaritis@mail.magee.edu

412 641 5256

Study Officials

• Steve N Caritis, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of OB/Gyn/RS

Model Details: An open labelled rct for secondary analysis of safety of 500 mg dose. A pharmacodynamic study of 17-OHPC concentration and rate of sPTB

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 26, 2017
• Study Start: February 12, 2018
• Primary Completion: September 2, 2021
• Study Completion: September 2, 2021
• Last Updated: October 23, 2023
• Results First Posted: October 23, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• 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.
• Access Criteria: To be determined by the OPRC steering committee.

Locations

US (5)