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Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth

Phase 4
Completed
Conditions
Premature Birth
Interventions
Drug: Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
Registration Number
NCT02913495
Lead Sponsor
Thomas Jefferson University
Brief Summary

The purpose of this study is to evaluate the two suggested therapies for prevention of recurrent preterm birth (PTB) in women with a prior spontaneous preterm birth, vaginal and intramuscular progesterone to determine whether vaginal progesterone is superior to intramuscular progesterone in the prevention of recurrent preterm birth.

Detailed Description

Preterm birth is one of the leading causes of neonatal morbidity and mortality. One of the greatest predictors of preterm birth is a history of prior spontaneous preterm birth. Presently 17 hydroxyprogesterone caproate (intramuscular) is the only FDA approved product for the prevention of recurrent preterm birth, however recent studies suggest that vaginal progesterone may be used for this purpose, and may even be superior. The American College of Obstetrics and Gynecology does not specify the optimal route of progesterone administration for the prevention of recurrent preterm birth. It is our intention to compare vaginal and intramuscular progesterone to see if one is superior.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
205
Inclusion Criteria
  • Pregnant women with singleton pregnancies
  • ≥18 years old
  • Estimated gestational age less than 24 0/7 weeks
  • Prior spontaneous preterm birth of a singleton pregnancy between 16 0/7-36 6/7 weeks.
  • Patients are also required provide consent, demonstrate an understanding of the purpose of the study, and agree to the study protocol.
Exclusion Criteria
  • History of an adverse reaction to progesterone;
  • A contraindication to progesterone treatment;
  • Placenta previa or accreta;
  • Major fetal anomaly diagnosed on ultrasound or known chromosomal disorder;
  • Multifetal gestation;
  • Preterm labor, premature rupture of membranes, or clinical chorioamnionitis, at the time of enrollment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intramuscular ProgesteroneIntramuscular Progesterone (17 alpha hydroxprogesterone caproate)250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Vaginal ProgesteroneVaginal Progesterone200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Primary Outcome Measures
NameTimeMethod
Preterm birth <37 weeksup to 9 months (delivery)

Incidence of gestational age of delivery less than 37 weeks

Secondary Outcome Measures
NameTimeMethod
Gestational age of deliveryup to 9 months (delivery)
Second trimester cervical length <25mm2 months
Preterm birth <34 weeks and <28 weeksup to 9 months (delivery)
Mode of deliveryup to 9 months (delivery)

Delivery mode- vaginal, cesarean, operative vaginal

Maternal mortalityup to 9 months (delivery)
5 minute Apgar scoreup to 9 months (delivery)
Neonatal intensive care unit admissionup to 9 months (delivery)
Composite neonatal morbidityup to 9 months (delivery)

(respiratory distress syndrome, grade III or IV intraventricular hemorrhage, culture proven sepsis, neonatal enterocolitis, and perinatal mortality up to 28 days of life)

Birthweightup to 9 months (delivery)
Perinatal mortality up to 28 days of lifeup to 10 months (4 weeks after delivery)
Medication side effectsup to 9 months (delivery)
Satisfaction with medication (5 point Likert scale)up to 9 months (delivery)
Medication adherenceup to 9 months (delivery)

Vaginal progesterone:

* Overall adherence: #days used/#days of treatment x 100

* Non-adherent: ≥4 days between doses

Intramuscular progesterone:

* Overall adherence: #weeks used/#weeks of treatment x 100

* Non-adherent: ≥10 days between doses

Planned subgroup analysis for the outcome preterm birth <37 weeks, <34 weeks, <28 weeksup to 9 months (delivery)

Planned subgroup analysis for the primary outcome as well as the secondary outcomes of preterm birth \<34 weeks and \<28 weeks of patients with a cervical length \<25mm versus ≥25mm, history-indicated cerclage versus not, and for those started on progesterone 16-20 weeks versus 20-24 weeks.

Trial Locations

Locations (3)

Baystate Medical Center

🇺🇸

Springfield, Massachusetts, United States

Thomas Jefferson University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

George Washington University

🇺🇸

Washington, District of Columbia, United States

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