Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth

Study Overview
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Brief Summary
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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
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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.

Official Title
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Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth

Conditions
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Premature Birth

Intervention / Treatment
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* Drug: Vaginal Progesterone
* Drug: Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaginal Progesterone<br>200mg 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 | Drug: Vaginal Progesterone<br> <br> * Other names: micronized progesterone;|
| Active Comparator: Intramuscular Progesterone<br>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. | Drug: Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)<br> <br> * Other names: Makena;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preterm birth <37 weeks | Incidence of gestational age of delivery less than 37 weeks | up to 9 months (delivery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gestational age of delivery |  | up to 9 months (delivery) | 
| Preterm birth <34 weeks and <28 weeks |  | up to 9 months (delivery) | 
| Second trimester cervical length <25mm |  | 2 months | 
| Mode of delivery | Delivery mode- vaginal, cesarean, operative vaginal | up to 9 months (delivery) | 
| Maternal mortality |  | up to 9 months (delivery) | 
| 5 minute Apgar score |  | up to 9 months (delivery) | 
| Neonatal intensive care unit admission |  | up to 9 months (delivery) | 
| Composite neonatal morbidity | (respiratory distress syndrome, grade III or IV intraventricular hemorrhage, culture proven sepsis, neonatal enterocolitis, and perinatal mortality up to 28 days of life) | up to 9 months (delivery) | 
| Birthweight |  | up to 9 months (delivery) | 
| Perinatal mortality up to 28 days of life |  | up to 10 months (4 weeks after delivery) | 
| Medication side effects |  | up to 9 months (delivery) | 
| Satisfaction with medication (5 point Likert scale) |  | up to 9 months (delivery) | 
| Medication adherence | 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 | up to 9 months (delivery) | 
| Planned subgroup analysis for the outcome preterm birth <37 weeks, <34 weeks, <28 weeks | 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. | up to 9 months (delivery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progesterone, Prevention of preterm birth