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

Purpose

The study plans to determine the relationship between plasma concentrations of 17-OHPC (hydroxyprogesterone caproate) and the rate of preterm birth. The study is a randomized, open label study of pregnant women with one or more prior spontaneous preterm births. Subjects are randomized to a weekly single injection of either 250 or 500mg 17-OHPC (hydroxyprogesterone caproate).

Condition

  • Preterm Birth

Eligibility

Eligible Ages
Between 18 Years and 45 Years
Eligible Genders
Female
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • pregnant with a prior preterm birth 16 0/7-35 6/7 weeks from spontaneous labor or 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)

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
open labelled rct
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
hydroxyprogesterone caproate 250 mg
Pregnant subject will receive 250mg of hydroxyprogesterone caproate Intramuscular injection weekly from 16 0/7-36 6/7 weeks or delivery which ever occurs first.
  • Drug: Hydroxyprogesterone 250 Mg
    Pregnant subjects randomized to this study arm will receive a weekly Intramuscular injection of 250mg hydroxyprogesterone caproate injection weekly from 16 0/7 to 36 6/7 weeks or delivery which ever is first.
Experimental
hydroxyprogesterone caproate 500 mg
Pregnant subject will receive 500mg of hydroxyprogesterone caproate Intramuscular injection weekly from 16 0/7-36 6/7 weeks or delivery which ever occurs first.
  • Drug: hydroxyprogesterone 500mg
    Pregnant subjects randomized to this study arm will receive a weekly Intramuscular injection of 500mg hydroxyprogesterone caproate injection weekly from 16 0/7 to 36 6/7 weeks or delivery which ever is first.

Recruiting Locations

University of Texas Medical Branch
Galveston, Texas 77555
Contact:
Shannon Clark, MD
409-772-5313
shclark@UTMB.edu

More Details

NCT ID
NCT03292731
Status
Recruiting
Sponsor
Steve N. Caritis, MD

Study Contact

steve N Caritis, MD
412-641-5403
scaritis@mail.magee.edu

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 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.

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. We will also collect a small sample of the placenta after delivery.