Premature Birth
Conditions
Keywords
Progesterone, Prevention of preterm birth
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.
Interventions
DRUGVaginal Progesterone
DRUGIntramuscular Progesterone (17 alpha hydroxprogesterone caproate)
Sponsors
Thomas Jefferson University
Baystate Medical Center
George Washington University
Vriginia Commonwealth University
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Preterm Birth <37 Weeks | up to 9 months (delivery) | Incidence of gestational age of delivery less than 37 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gestational Age of Delivery | up to 9 months (delivery) | Gestational age at delivery (weeks) |
| Preterm Birth <34 Weeks | up to 9 months (delivery) | Delivery of pregnancy 20 0/7 - 33 6/7 weeks gestation |
| Second Trimester Cervical Length <25mm | 2 months | Short cervix diagnosis (transvaginal ultrasound cervical length \<=25mm prior to 24 weeks gestation |
| Mode of Delivery: Cesarean Section | up to 9 months (delivery) | Delivery mode- vaginal, cesarean, operative vaginal |
| Maternal Mortality | up to 9 months (delivery) | Maternal death for any reason from enrollment through hospital discharge from delivery hospitalization. |
| 5 Minute Apgar Score<7 | up to 9 months (delivery) | The Apgar score is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. A score of 7, 8, or 9 is normal and is a sign that the newborn is in good health. |
| Neonatal Intensive Care Unit Admission | up to 9 months (delivery) | Admission to neonatal intensive care unit for any reason (yes/no) |
| Composite Neonatal Morbidity | up to 9 months (delivery) | Having at least one of the following: respiratory distress syndrome, grade III or IV intraventricular hemorrhage, culture proven sepsis, neonatal enterocolitis, or perinatal mortality up to 28 days of life |
| Birthweight | up to 9 months (delivery) | Birthweight assessed at delivery (grams) |
| Perinatal Mortality up to 28 Days of Life | up to 10 months (4 weeks after delivery) | In utero or neonatal death from enrollment through 28 days of neonatal life. |
| Medication Side Effects | up to 9 months (delivery) | Medication side effects |
| Satisfaction With Medication (5 Point Likert Scale) | up to 9 months (delivery) | 5 point scale, 0 is very dissatisfied, 5 is very satisfied, 3 is neutral |
| Medication Adherence | up 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 Weeks | up to 9 months (delivery) | Planned subgroup analysis for the primary outcome 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRupsa C Boelig, MD
Thomas Jefferson University Hospital; Sidney Kimmel Medical College
Participant flow
Recruitment details
Enrollment 2016 - 2021
Pre-assignment details
5 excluded (N=2 miscarriage, N=3 withdrawal) prior to randomization
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 28.9 years STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 143 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 51 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 90 Participants |
| Region of Enrollment United States | 188 participants |
| Sex: Female, Male Female | 188 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 94 | 0 / 94 |
| other Total, other adverse events | 24 / 94 | 27 / 94 |
| serious Total, serious adverse events | 0 / 94 | 0 / 94 |
Outcome results
None listed