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RCT of Progesterone to Prevent Preterm Birth in Nulliparous Women With a Short Cervix

Phase 3
Terminated
Conditions
Preterm Delivery
Cervical Length
Interventions
Drug: 17 alpha-hydroxyprogesterone caproate
Other: Placebo Oil
Registration Number
NCT00439374
Lead Sponsor
The George Washington University Biostatistics Center
Brief Summary

The purpose of this study is to see if giving progesterone medication to pregnant women, who have never delivered a baby after 19 weeks of pregnancy and who have a short cervix, lowers the risk of early delivery and improves the health of their baby.

Detailed Description

Preterm births, defined as the delivery of a baby less than 37 weeks of gestation, are responsible for the majority of neonatal mortality and morbidities. Studies have shown that a number of risk factors, including never having a baby before and having a short cervix are associated with early delivery. Recently the NICHD did a study in women who were pregnant again after having delivered preterm. It showed that giving 17 alpha-hydroxyprogesterone caproate (17P) medication during pregnancy decreased the chance of delivering another preterm baby by 34%. This placebo-controlled randomized clinical trial will address the primary research question: does treatment with 17P initiated before 23 weeks of gestation prevent delivery prior to 37 weeks in nulliparous women with a singleton gestation who have a short cervix?

Recruitment & Eligibility

Status
TERMINATED
Sex
Female
Target Recruitment
657
Inclusion Criteria
  • Nulliparous
  • Cervical length as measured on transvaginal examination < 30mm between gestational ages of 16 weeks 0 days to 22 weeks 3 days
  • Gestational age 16 weeks 3 days to 22 weeks 6 days at time of randomization
Exclusion Criteria
  • Multifetal gestation
  • Progesterone treatment after 14 weeks 6 days during current pregnancy
  • Vaginal bleeding, heavier than spotting, after 15 weeks 6 days
  • Amniotic membranes prolapsed beyond external os
  • Preterm rupture of membranes
  • Fetal anomaly
  • Pregnancy without a viable fetus
  • Current or planned cervical cerclage
  • Congenital Mullerian abnormality of the uterus
  • Contraindication to intra-muscular injections
  • Hypertension requiring medication
  • Diabetes managed with insulin or oral hypoglycemic agents
  • DES exposure
  • Cervical surgery such as cold knife conization
  • Planned indicated preterm delivery
  • Participation in another interventional study that influences age at delivery
  • Participation in this trial in a previous pregnancy
  • Prenatal care or delivery planned outside a MFMU Network center

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
17 alpha-hydroxyprogesterone caproate17 alpha-hydroxyprogesterone caproate250 mg of 17 alpha-hydroxyprogesterone caproate given by weekly injection until 37 weeks gestation or delivery
PlaceboPlacebo OilPlacebo oil given by weekly injection until 37 weeks gestation or delivery.
Primary Outcome Measures
NameTimeMethod
Number of Participants Delivering Before 37 Weeks GestationDelivery before 37 weeks gestation

Number of participants delivering before 37 weeks gestation by indication

Secondary Outcome Measures
NameTimeMethod
Mean Gestational Age at DeliveryDelivery

Mean gestational age at delivery

Number of Participants With Gestational Diabetes MellitusAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Delivered Before 28 Weeks GestationDelivery

Delivery before 28 weeks gestation

Number of Participants With Preterm Premature Rupture of Membranes<37 weeks
Number of Participants Who Delivered Before 35 Weeks GestationDelivery

Delivery before 35 weeks gestation

Number of Participants Who Delivered Before 32 Weeks GestationDelivery

Delivery before 32 weeks gestation

Number of Participants Who Visited the Hospital Due to Preterm LaborBetween randomization and 37 weeks gestation

Number of participants who visited the hospital due to preterm labor before 37 weeks gestation

Number of Participants Who Underwent Tocolytic TherapyAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Number of participants who underwent tocolytic therapy during pregnancy

Number of Participants Who Underwent Corticosteroid TherapyAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Number of participants who underwent corticosteroid therapy in pregnancy

Number of Participants Who Had a Cerclage PlacementAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Number of participants who had a cerclage placement

Number of Participants Experiencing Gestational Hypertension or PreeclampsiaAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Experiencing CholestasisAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Experienced Placental AbruptionAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Had Cesarean Deliverydelivery
Number of Participants Meeting the Composite Adverse Perinatal Outcome and Componentswithin 72 hours of delivery

comprised of fetal or infant death, respiratory distress syndrome, intraventricular hemorrhage (grades 3 and 4), periventricular leukomalacia, necrotizing enterocolitis (stage II and III), Bronchopulmonary dysplasia /chronic lung disease, retinopathy of prematurity (stage III or higher), early onset sepsis

Mean Birth WeightDelivery

Birth weight as measured in grams

Birth Weight by Count of ParticipantsDelivery

Birth weight by count of participants \< 2500 grams and \< 1500 grams

Number of Neonates Who Measured Small for Gestational AgeDelivery

Birth weight percentile and small for gestational age \<10th percentile based on number of weeks and gender.

Number of Neonates With a Major Congenital AnomalyDelivery

Presence of a major congenital anomaly at birth

Number of Participants Who Experienced ChorioamnionitisAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Reported Side EffectsAny time during pregnancy from randomization to delivery, a timeframe up to 20 weeks

Number of participants who reported any side effect, nausea, urticaria, and/or an issue at the injection site

Number of Participants With Apgar Score of Less Than 7 at 5 Minutes5 minutes post delivery

The Apgar score is a simple method of quickly assessing the health and vital signs of a newborn baby created by and named after Dr. Virginia Apgar. Apgar testing assesses Appearance, Pulse, Grimace and Activity in a newborn and is typically done at one and five minutes after a baby is born, and it may be repeated at 10, 15, and 20 minutes if the score is low. The five criteria are each scored as 0, 1, or 2 (two being the best), and the total score is calculated by then adding the five values obtained. Agar scores of 0-3 are critically low, 4-6 are below normal, and indicate that the baby likely requires medical intervention, scores of 7+ are considered normal. The lower the Apgar score, the more alert the medical team should be to the possibility of the baby requiring intervention. Some components of the Apgar score are subjective, and there are cases in which a baby requires urgent medical treatment despite having a high Apgar score.

Number of Neonates With Patent Ductus ArteriosusDelivery through neonatal discharge

Number of neonates diagnosed with the heart defect patent ductus arteriosus

Number of Neonates Experiencing SeizuresDelivery through neonatal discharge

Number of neonates experiencing seizures from delivery to hospital discharge

Number of Neonates Admitted to NICUDelivery through hospital discharge

Admission to the neonatal intensive care unit

Median Length of NICU StayNICU admission through NICU discharge

Median length of stay in the neonatal intensive care unit in days

Trial Locations

Locations (14)

University of North Carolina - Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Dept of OB/GYN, Hutzel Hospital

🇺🇸

Detroit, Michigan, United States

University of Texas-Houston

🇺🇸

Houston, Texas, United States

Northwestern University-Prentice Hospital

🇺🇸

Chicago, Illinois, United States

Case Western Reserve-Metrohealth

🇺🇸

Cleveland, Ohio, United States

Ohio State University Hospital

🇺🇸

Columbus, Ohio, United States

University of Pittsburgh-Magee Womens Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Dept of OB/GYN, Southwestern Medical Center, University of Texas

🇺🇸

Dallas, Texas, United States

University of Utah Medical Center

🇺🇸

Salt Lake City, Utah, United States

Columbia University-St. Luke's Hospital

🇺🇸

New York, New York, United States

University of Texas Medical Branch - Galveston

🇺🇸

Galveston, Texas, United States

Brown University -Women and Infants Hospital

🇺🇸

Providence, Rhode Island, United States

University of Alabama - Birmingham

🇺🇸

Birmingham, Alabama, United States

Oregon Health & Sciences University

🇺🇸

Portland, Oregon, United States

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