title: 17-hydroxyprogesterone caproate for preterm rupture of the membranes: a multicenter, randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  Preterm rupture of membranes (PROM) is associated with an increased risk of preterm birth and neonatal morbidity. Prophylactic 17-hydroxyprogesterone caproate (17OHP-C) reduces the risk of preterm birth in some women who are at risk for preterm birth. We sought to test whether 17OHP-C would prolong pregnancy or improve perinatal outcome when given to mothers with preterm rupture of the membranes.
  
  
  METHODS
  This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. The study included singleton pregnancies with gestational ages from 23(0/7) to 30(6/7) weeks at enrollment, documented PROM, and no contraindication to expectant management. Consenting women were assigned randomly to receive weekly intramuscular injections of 17OHP-C (250 mg) or placebo. The primary outcome was continuation of pregnancy until a favorable gestational age, which was defined as either 34(0/7) weeks of gestation or documentation of fetal lung maturity at 32(0/7) to 33(6/7) weeks of gestation. The 2 prespecified secondary outcomes were interval from randomization to delivery and composite adverse perinatal outcome. The planned sample size was 222 total women.
  
  
  RESULTS
  From October 2011 to April 2014, 152 women were enrolled; 74 women were allocated randomly to 17OHP-C, and 78 were allocated randomly to placebo. The trial was stopped when results of a planned interim analysis suggested that continuation was futile. The primary outcome was achieved in 3% of the 17OHP-C group and 8% of the placebo group (P = .18). There was no significant between-group difference in the prespecified secondary outcomes, randomization-to-delivery interval (17.1 ± 16.1 vs 17.0 ± 15.8 days, respectively; P = .76) or composite adverse perinatal outcome (63% vs 61%, respectively; P = .93). No significant differences were found in other outcomes, which included rates of chorioamnionitis, postpartum endometritis, cesarean delivery, individual components of the composite outcome, or prolonged neonatal length of stay.
  
  
  CONCLUSIONS
  Compared with placebo, weekly 17OHP-C injections did not prolong pregnancy or reduce perinatal morbidity in patients with PROM in this trial.
authors.affiliation: Center for Research, Education, and Quality, Obstetrix, Mednax National Medical Group, Sunrise, FL; Obstetrix Medical Group, San Jose, CA. Electronic address: andrewcombs@me.com.
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Combs
authors.affiliation: Center for Research, Education, and Quality, Obstetrix, Mednax National Medical Group, Sunrise, FL; Department of Obstetrics and Gynecology, University of California, Irvine, School of Medicine, Irvine, CA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Garite
authors.affiliation: Center for Research, Education, and Quality, Obstetrix, Mednax National Medical Group, Sunrise, FL.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Maurel
authors.affiliation: Center for Research, Education, and Quality, Obstetrix, Mednax National Medical Group, Sunrise, FL.
authors.forename: Diana
authors.initials: D
authors.lastname: Abril
authors.affiliation: Biometrics, San Francisco, CA.
authors.forename: Anita
authors.initials: A
authors.lastname: Das
authors.affiliation: Obstetrix Medical Group, Phoenix Perinatal Associates, Phoenix, AZ.
authors.forename: William
authors.initials: W
authors.lastname: Clewell
authors.affiliation: Obstetrix Medical Group, Denver, CO.
authors.forename: Kent
authors.initials: K
authors.lastname: Heyborne
authors.affiliation: Norton Healthcare, Louisville, KY.
authors.forename: Helen
authors.initials: H
authors.lastname: How
authors.affiliation: High Risk Pregnancy Center, Las Vegas, NV.
authors.forename: Wilson
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, University of South Alabama School of Medicine, Mobile, AL.
authors.forename: David
authors.initials: D
authors.lastname: Lewis
authors.affiliation: Obstetrix Medical Group, Kansas City, MO.
authors.forename: George
authors.initials: G
authors.lastname: Lu
authors.affiliation: Obstetrix Medical Group, Tucson, AZ.
authors.forename: Hugh
authors.initials: H
authors.lastname: Miller
authors.affiliation: Obstetrix Medical Group, Long Beach, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nageotte
authors.affiliation: Obstetrix Medical Group, Denver, CO.
authors.forename: Richard
authors.initials: R
authors.lastname: Porreco
authors.affiliation: Spectrum Health, Grand Rapids, MI.
authors.forename: Asad
authors.initials: A
authors.lastname: Sheikh
authors.affiliation: Obstetrix Medical Group, Seattle, WA.
authors.forename: Lan
authors.initials: L
authors.lastname: Tran
mesh_terms: D000077713:17 alpha-Hydroxyprogesterone Caproate; D000328:Adult; D002543:Cerebral Hemorrhage / Q000453:epidemiology; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000188:drug therapy*; D005865:Gestational Age; D006801:Humans; D006908:Hydroxyprogesterones / Q000627:therapeutic use*; D007231:Infant, Newborn; D007234:Infant, Premature; D007273:Injections, Intramuscular; D007969:Leukomalacia, Periventricular / Q000453:epidemiology; D054238:Perinatal Mortality; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011372:Progestins / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012127:Respiratory Distress Syndrome, Newborn / Q000453:epidemiology; D018805:Sepsis / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D057832:Watchful Waiting; D055815:Young Adult
chemical_list: D006908:Hydroxyprogesterones; D011372:Progestins; D000077713:17 alpha-Hydroxyprogesterone Caproate
keywords: 17-hydroxyprogesterone caproate; preterm rupture of membranes; prevention of preterm birth