Clinical trial NCT00439374: RCT of Progesterone to Prevent Preterm Birth in Nulliparous Women With a Short Cervix
Official title: A Randomized Trial of 17 Alpha-Hydroxyprogesterone Caproate for Prevention of Preterm Birth in Nulliparous Women With a Short Cervix
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Preterm Delivery
Cervical Length
Keywords: nulliparous
pregnancy
short cervix
progesterone
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2007-02-23
Enrollment: 657
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment with 17 alpha-hydroxyprogesterone caproate via weekly injections of 250 mg of 17p until 37 weeks gestation or delivery vs. weekly injections of placebo oil until 37 weeks gestation or delivery.
Primary purpose: PREVENTION

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?

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Delivering Before 37 Weeks Gestation
timeFrame: Delivery before 37 weeks gestation
Secondary outcomes:
measure: Mean Gestational Age at Delivery
timeFrame: Delivery
measure: Number of Participants With Preterm Premature Rupture of Membranes
timeFrame: <37 weeks
measure: Number of Participants Who Delivered Before 35 Weeks Gestation
timeFrame: Delivery
measure: Number of Participants Who Delivered Before 32 Weeks Gestation
timeFrame: Delivery
measure: Number of Participants Who Delivered Before 28 Weeks Gestation
timeFrame: Delivery
measure: Number of Participants Who Visited the Hospital Due to Preterm Labor
timeFrame: Between randomization and 37 weeks gestation
measure: Number of Participants Who Underwent Tocolytic Therapy
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants Who Underwent Corticosteroid Therapy
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants Who Had a Cerclage Placement
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants Experiencing Gestational Hypertension or Preeclampsia
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants With Gestational Diabetes Mellitus
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants Experiencing Cholestasis
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants Who Experienced Placental Abruption
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants Who Experienced Chorioamnionitis
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants Who Had Cesarean Delivery
timeFrame: delivery
measure: Number of Participants Who Reported Side Effects
timeFrame: Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
measure: Number of Participants Meeting the Composite Adverse Perinatal Outcome and Components
timeFrame: within 72 hours of delivery
measure: Mean Birth Weight
timeFrame: Delivery
measure: Birth Weight by Count of Participants
timeFrame: Delivery
measure: Number of Neonates Who Measured Small for Gestational Age
timeFrame: Delivery
measure: Number of Participants With Apgar Score of Less Than 7 at 5 Minutes
timeFrame: 5 minutes post delivery
measure: Number of Neonates With a Major Congenital Anomaly
timeFrame: Delivery
measure: Number of Neonates With Patent Ductus Arteriosus
timeFrame: Delivery through neonatal discharge
measure: Number of Neonates Experiencing Seizures
timeFrame: Delivery through neonatal discharge
measure: Number of Neonates Admitted to NICU
timeFrame: Delivery through hospital discharge
measure: Median Length of NICU Stay
timeFrame: NICU admission through NICU discharge
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Chicago
country: United States
facility: Northwestern University-Prentice Hospital
state: Illinois
city: Detroit
country: United States
facility: Dept of OB/GYN, Hutzel Hospital
state: Michigan
city: New York
country: United States
facility: Columbia University-St. Luke's Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve-Metrohealth
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh-Magee Womens Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Brown University -Women and Infants Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Dept of OB/GYN, Southwestern Medical Center, University of Texas
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch - Galveston
state: Texas
city: Houston
country: United States
facility: University of Texas-Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
affiliation: Northwestern University
name: William Grobman, MD, MBA
role: PRINCIPAL_INVESTIGATOR
affiliation: NICHD Project Scientist
name: Menachem Miodovnik, MD
role: STUDY_DIRECTOR
References:
citation: Grobman WA, Thom EA, Spong CY, Iams JD, Saade GR, Mercer BM, Tita AT, Rouse DJ, Sorokin Y, Wapner RJ, Leveno KJ, Blackwell S, Esplin MS, Tolosa JE, Thorp JM Jr, Caritis SN, Van Dorsten JP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol. 2012 Nov;207(5):390.e1-8. doi: 10.1016/j.ajog.2012.09.013. Epub 2012 Sep 17.