Clinical trial NCT00015002: Repeat Antenatal Steroids Trial
Official title: A Randomized Placebo-Controlled Trial of Antenatal Corticosteroid Regimens
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Complications, Pregnancy
Keywords: Antenatal corticosteroids
Preterm delivery
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: 2001-04-18
Enrollment: 486
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A course of steroids given to a mother who is in labor with a premature fetus will reduce the risk of the premature infant dying or having serious complications. This trial will test whether more than one course of antenatal steroids is more beneficial or risky to the infant than a single course.

Detailed description: After the NICHD Consensus Development Conference in 1994, the antenatal administration of antenatal corticosteroids (betamethasone or dexamethasone) for prevention of death and the serious morbidities associated with preterm birth has become an accepted standard in American obstetric practice. Studies have shown that maximum beneficial effect occurs when the fetus is delivered within 7 days of antenatal steroid administration. The efficacy and safety of a single course of corticosteroids has been substantiated but it is unknown whether repetitive dosing has similar efficacy or what the maternal, fetal and neonatal risks are. Repeat courses of steroids are often administered. Two popular regimens exist for the patient who remains undelivered more than one week after initial therapy but who remains at risk for preterm birth. In one, steroids are repeated weekly until 34 weeks gestation, while in the other, steroids are only given once.

This multicenter trial is testing the safety and efficacy of weekly administration of antenatal steroids. Twenty four hundred women \< 32.0 weeks gestation who are at risk for spontaneous preterm delivery and remain pregnant at least seven days after an initial course of corticosteroids are being randomized to either weekly courses of masked study drug (betamethasone or placebo) for 4 weeks or delivery, whichever comes first. Patients are asked about side effects at the weekly visits and samples of maternal blood at randomization and delivery are collected. Cord blood and placentas are also collected. Cranial ultrasounds are done on all neonates. On a subgroup of patients, an adrenocorticotrophic hormone (ACTH) stimulation test is being performed and an auditory brainstem response (ABR) performed. All infants attend a follow-up visit at 18 to 22 months corrected age where certified examiners, masked to study group assignment, collect physical and neurological data. The Bayley Scales of Infant Development will also be administered. A subgroup of infants will be seen at 36 months to administer the Intelligence scale from the McCarthy Scales of Children's Abilities.

Eligibility criteria: Inclusion criteria:

* Pregnant
* Gestational age \> 23.0 wks and \< 31.6 wks
* Singleton or twin pregnancy
* Intact membranes
* At-risk for spontaneous preterm delivery
* Received full course of corticosteroids within the previous 7 days

Exclusion criteria:

* Diagnosis of fetal lung maturity
* Chorioamnionitis
* Non-reassuring fetal testing
* Known major fetal anomaly
* Corticosteroid therapy, other than qualifying course
* Insulin dependent diabetes
* Active preterm labor at the time of randomization
* Delivery intended outside center
* Participation in any intervention study which influences neonatal morbidity or mortality
* Previous participation in this trial

Primary outcomes:
measure: Composite outcome: including neonatal mortality/stillbirth, severe RDS, chronic lung disease, grade III/IV IVH, PVL
Secondary outcomes:
measure: Neonatal morbidity
measure: Maternal morbidity
measure: Neonatal Growth parameters
measure: Infant neurological parameters
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Northwestern University-Prentice Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
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
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Memorial Hospital, Wake Forest University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve-Metrohealth
state: Ohio
city: Columbus
country: United States
facility: Dept of OB/GYN, Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: MCP Hahnamann
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Dept of OB/GYN, Magee-Womens Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Brown University -Women and Infants Hospital
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Dallas
country: United States
facility: Dept of OB/GYN, Southwestern Medical Center, University of Texas
state: Texas
city: Houston
country: United States
facility: University of Texas-Houston
state: Texas
city: San Antonio
country: United States
facility: University of Texas - San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
affiliation: MCP Hahnemann University Hospital
name: Ronald J Wapner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972 Oct;50(4):515-25. No abstract available.
citation: Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol. 1995 Jul;173(1):322-35. doi: 10.1016/0002-9378(95)90222-8. No abstract available.
citation: French NP, Hagan R, Evans SF, Godfrey M, Newnham JP. Repeated antenatal corticosteroids: size at birth and subsequent development. Am J Obstet Gynecol. 1999 Jan;180(1 Pt 1):114-21. doi: 10.1016/s0002-9378(99)70160-2.
citation: Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. JAMA. 1995 Feb 1;273(5):413-8. doi: 10.1001/jama.1995.03520290065031.
citation: Gamsu HR, Mullinger BM, Donnai P, Dash CH. Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial. Br J Obstet Gynaecol. 1989 Apr;96(4):401-10. doi: 10.1111/j.1471-0528.1989.tb02413.x.
citation: Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. Am J Obstet Gynecol. 1981 Oct 1;141(3):276-87.
citation: Wright LL. Evidence from multicenter networks on the current use and effectiveness of antenatal corticosteroids in very low birthweight infants. In: National Institute of Child Health and Development (US). Report on the Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes; 1994 Feb 28-Mar 2; Bethesda, (MD): The Institute; 1994 Nov. P. 47-8. (NIH Publication; no. 95-3784).
citation: Wapner RJ, Sorokin Y, Thom EA, Johnson F, Dudley DJ, Spong CY, Peaceman AM, Leveno KJ, Harper M, Caritis SN, Miodovnik M, Mercer B, Thorp JM, Moawad A, O'Sullivan MJ, Ramin S, Carpenter MW, Rouse DJ, Sibai B, Gabbe SG; National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am J Obstet Gynecol. 2006 Sep;195(3):633-42. doi: 10.1016/j.ajog.2006.03.087. Epub 2006 Jul 17.
citation: Carroll MA, Vidaeff AC, Mele L, Wapner RJ, Mercer B, Peaceman AM, Sorokin Y, Dudley DJ, Spong CY, Leveno KJ, Harper M, Caritis SN, Miodovnik M, Thorp JM, Moawad A, O'Sullivan MJ, Carpenter MW, Rouse DJ, Sibai B; National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units Network (MFMU). Bone metabolism in pregnant women exposed to single compared with multiple courses of corticosteroids. Obstet Gynecol. 2008 Jun;111(6):1352-8. doi: 10.1097/AOG.0b013e318173573b.
citation: Fonseca L, Ramin SM, Mele L, Wapner RJ, Johnson F, Peaceman AM, Sorokin Y, Dudley DJ, Spong CY, Leveno KJ, Caritis SN, Miodovnik M, Mercer B, Thorp JM, O'Sullivan MJ, Carpenter MW, Rouse DJ, Sibai B; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units Network (MFMU). Bone metabolism in fetuses of pregnant women exposed to single and multiple courses of corticosteroids. Obstet Gynecol. 2009 Jul;114(1):38-44. doi: 10.1097/AOG.0b013e3181a82b85.
citation: Sawady J, Mercer BM, Wapner RJ, Zhao Y, Sorokin Y, Johnson F, Dudley DJ, Spong CY, Peaceman AM, Leveno KJ, Harper M, Caritis SN, Miodovnik M, Thorp JM, Ramin S, Carpenter MW, Rouse DJ; National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Beneficial Effects of Antenatal Repeated Steroids study: impact of repeated doses of antenatal corticosteroids on placental growth and histologic findings. Am J Obstet Gynecol. 2007 Sep;197(3):281.e1-8. doi: 10.1016/j.ajog.2007.06.041.
citation: Wapner RJ, Sorokin Y, Mele L, Johnson F, Dudley DJ, Spong CY, Peaceman AM, Leveno KJ, Malone F, Caritis SN, Mercer B, Harper M, Rouse DJ, Thorp JM, Ramin S, Carpenter MW, Gabbe SG; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Long-term outcomes after repeat doses of antenatal corticosteroids. N Engl J Med. 2007 Sep 20;357(12):1190-8. doi: 10.1056/NEJMoa071453.