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

A Randomized Trial of 17 Alpha-Hydroxyprogesterone Caproate for Prevention of Preterm Birth in Nulliparous Women With a Short Cervix

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.

Study Overview

• Status: Terminated
• Conditions: Cervical Length; Preterm Delivery
• Intervention / Treatment: Drug: 17 alpha-hydroxyprogesterone caproate; Other: Placebo Oil

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?

• Study Type: Interventional
• Enrollment (Actual): 657
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35429
      • University of Alabama - Birmingham
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University-Prentice Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Dept of OB/GYN, Hutzel Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University-St. Luke's Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina - Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • Case Western Reserve-Metrohealth
    • Columbus, Ohio, United States, 43210
      • Ohio State University Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh-Magee Womens Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02095
      • Brown University -Women and Infants Hospital
  • Texas
    • Dallas, Texas, United States, 75235-9032
      • Dept of OB/GYN, Southwestern Medical Center, University of Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch - Galveston
    • Houston, Texas, United States, 77030
      • University of Texas-Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 17 alpha-hydroxyprogesterone caproate; 250 mg of 17 alpha-hydroxyprogesterone caproate given by weekly injection until 37 weeks gestation or delivery	Drug: 17 alpha-hydroxyprogesterone caproate; Coded study medication is sterile solution containing 250 mg/mL of 17 alpha-hydroxyprogesterone caproate in castor oil with benzyl benzoate and benzyl alcohol as a preservative; placebo is same without the active ingredient. Study drug is administered as weekly 1 ml intramuscular injections until 36 week 6 days of gestation or delivery, whichever occurs first.; Other Names: 17 AHP
Placebo Comparator: Placebo; Placebo oil given by weekly injection until 37 weeks gestation or delivery.	Other: Placebo Oil; Placebo oil is a 250 mg/mL solution of castor oil with benzyl benzoate and benzyl alcohol as a preservative

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Delivering Before 37 Weeks Gestation	Number of participants delivering before 37 weeks gestation by indication	Delivery before 37 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Gestational Age at Delivery	Mean gestational age at delivery	Delivery
Number of Participants With Preterm Premature Rupture of Membranes		<37 weeks
Number of Participants Who Delivered Before 35 Weeks Gestation	Delivery before 35 weeks gestation	Delivery
Number of Participants Who Delivered Before 32 Weeks Gestation	Delivery before 32 weeks gestation	Delivery
Number of Participants Who Delivered Before 28 Weeks Gestation	Delivery before 28 weeks gestation	Delivery
Number of Participants Who Visited the Hospital Due to Preterm Labor	Number of participants who visited the hospital due to preterm labor before 37 weeks gestation	Between randomization and 37 weeks gestation
Number of Participants Who Underwent Tocolytic Therapy	Number of participants who underwent tocolytic therapy during pregnancy	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Underwent Corticosteroid Therapy	Number of participants who underwent corticosteroid therapy in pregnancy	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Had a Cerclage Placement	Number of participants who had a cerclage placement	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Experiencing Gestational Hypertension or Preeclampsia		Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants With Gestational Diabetes Mellitus		Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Experiencing Cholestasis		Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Experienced Placental Abruption		Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Experienced Chorioamnionitis		Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Who Had Cesarean Delivery		delivery
Number of Participants Who Reported Side Effects	Number of participants who reported any side effect, nausea, urticaria, and/or an issue at the injection site	Any time during pregnancy from randomization to delivery, a timeframe up to 20 weeks
Number of Participants Meeting the Composite Adverse Perinatal Outcome and Components	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	within 72 hours of delivery
Mean Birth Weight	Birth weight as measured in grams	Delivery
Birth Weight by Count of Participants	Birth weight by count of participants < 2500 grams and < 1500 grams	Delivery
Number of Neonates Who Measured Small for Gestational Age	Birth weight percentile and small for gestational age <10th percentile based on number of weeks and gender.	Delivery
Number of Participants With Apgar Score of Less Than 7 at 5 Minutes	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.	5 minutes post delivery
Number of Neonates With a Major Congenital Anomaly	Presence of a major congenital anomaly at birth	Delivery
Number of Neonates With Patent Ductus Arteriosus	Number of neonates diagnosed with the heart defect patent ductus arteriosus	Delivery through neonatal discharge
Number of Neonates Experiencing Seizures	Number of neonates experiencing seizures from delivery to hospital discharge	Delivery through neonatal discharge
Number of Neonates Admitted to NICU	Admission to the neonatal intensive care unit	Delivery through hospital discharge
Median Length of NICU Stay	Median length of stay in the neonatal intensive care unit in days	NICU admission through NICU discharge

Collaborators and Investigators

• Sponsor: The George Washington University Biostatistics Center
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: William Grobman, MD, MBA, Northwestern University

Publications and helpful links

General Publications

• 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.

Helpful Links

• Click here for more information about the SCAN protocol

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 21, 2007
• First Submitted That Met QC Criteria: February 21, 2007
• First Posted (Estimate): February 23, 2007

Study Record Updates

• Last Update Posted (Actual): July 15, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: pregnancy; progesterone; short cervix; nulliparous
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Progestins; 17 alpha-Hydroxyprogesterone Caproate; 11-hydroxyprogesterone
• Other Study ID Numbers: HD36801 SCAN; U10HD036801 (U.S. NIH Grant/Contract); U10HD021410 (U.S. NIH Grant/Contract); U10HD027869 (U.S. NIH Grant/Contract); U10HD027917 (U.S. NIH Grant/Contract); U10HD034116 (U.S. NIH Grant/Contract); U10HD034208 (U.S. NIH Grant/Contract); U10HD034136 (U.S. NIH Grant/Contract); U10HD040500 (U.S. NIH Grant/Contract); U10HD040485 (U.S. NIH Grant/Contract); U10HD040544 (U.S. NIH Grant/Contract); U10HD040545 (U.S. NIH Grant/Contract); U10HD040560 (U.S. NIH Grant/Contract); U10HD040512 (U.S. NIH Grant/Contract); U10HD053097 (U.S. NIH Grant/Contract); U10HD027915 (U.S. NIH Grant/Contract); U10HD053118 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The dataset will be shared per NIH policy after the completion and publication of the main analyses. Requests for datasets can be sent to mfmudatasets@bsc.gwu.edu