Repeat Antenatal Steroids Trial

Condition(s) targeted: Complications, Pregnancy

Intervention: Betamethasone (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Official(s) and/or principal investigator(s):
Ronald J Wapner, MD, Principal Investigator, Affiliation: MCP Hahnemann University Hospital

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.

Official title: A Randomized Placebo-Controlled Trial of Antenatal Corticosteroid Regimens

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: Composite outcome: including neonatal mortality/stillbirth, severe RDS, chronic lung disease, grade III/IV IVH, PVL

Secondary outcome:

Neonatal morbidity

Maternal morbidity

Neonatal Growth parameters

Infant neurological parameters

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.

Minimum age: N/A. Maximum age: N/A. Gender(s): Female.

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

University of Alabama, Birmingham, Alabama 35294, United States

University of Miami, Miami, Florida 33136, United States

Northwestern University-Prentice Hospital, Chicago, Illinois 60611, United States

University of Chicago, Chicago, Illinois 60637, United States

Dept of OB/GYN, Hutzel Hospital, Detroit, Michigan 48201, United States

Columbia University, New York City, New York 10032, United States

University of North Carolina, Chapel Hill, North Carolina 27599, United States

Forsyth Memorial Hospital, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27103, United States

University of Cincinnati, Cincinnati, Ohio 45267, United States

Case Western Reserve-Metrohealth, Cleveland, Ohio 44109, United States

Dept of OB/GYN, Ohio State University, Columbus, Ohio 43210, United States

MCP Hahnamann, Philadelphia, Pennsylvania 19102, United States

Dept of OB/GYN, Magee-Womens Hospital, Pittsburgh, Pennsylvania 15213, United States

Brown University -Women and Infants Hospital, Providence, Rhode Island 02095, United States

University of Tennessee, Memphis, Tennessee 38103, United States

Dept of OB/GYN, Southwestern Medical Center, University of Texas, Dallas, Texas 75235-9032, United States

University of Texas-Houston, Houston, Texas 77030, United States

University of Texas - San Antonio, San Antonio, Texas 78284, United States

University of Utah Medical Center, Salt Lake City, Utah 84132, United States

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Related publications:

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.

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.

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.

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. Review.

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.

Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. Am J Obstet Gynecol. 1981 Oct 1;141(3):276-87.

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).

Starting date: March 2000
Last updated: January 1, 2010