Clinical trial NCT00201643: A Randomized Trial Comparing the Impact of One Versus Two Courses of Antenatal Steroids (ACS) on Neonatal Outcome
Official title: A Randomized Double-Blinded Study Comparing the Impact of One Versus Two Courses of Antenatal Steroids on Neonatal Outcome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Preterm Delivery
Keywords: Preterm Labor
Preterm delivery
Lead sponsor: Pediatrix
Sponsor class: OTHER
First posted: 2005-09-20
Enrollment: 437
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The hypothesis is that administration of two courses of antenatal corticosteroids, compared to one course, will show a 40% reduction in the incidence of composite neonatal morbidity in patients delivering prior to 34 weeks' gestation.

Detailed description: This is a randomized double-blinded placebo-controlled trial. The objective of this study is to evaluate the impact of one versus two courses of antenatal steroids on the incidence of major neonatal morbidity including respiratory distress syndrome in patients delivering prior to 34 weeks' gestation in a randomized prospective fashion.

Preterm delivery occurs in approximately 10% of all deliveries in the United States. Preterm birth is the cause of 75% of neonatal mortality not mentioning the significantly increased morbidity from respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis. Numerous studies have evaluated the safety and efficacy of antenatal corticosteroid (ACS) administration in threatened preterm labor.

National Institutes of Health (NIH) first consensus conference in 1994 evaluated the research in this field. Conclusions included the clear evidence that antenatal corticosteroids decrease the incidence of RDS in infants born at 29-34 weeks gestation, with a decrease in RDS severity for infants born at 24-28 weeks gestation and a decrease in the incidence of intraventricular hemorrhage in infants born at 24-28 weeks gestation without harm to mother or fetus. Their recommendation was to give a single course of corticosteroids to all pregnant women between 24 and 34 weeks gestation who are at risk of preterm delivery within 7 days.

Since the studies on the duration of the effects of antenatal corticosteroids in the fetus are not conclusive, many obstetricians repeat corticosteroids weekly or bi-weekly to patients continuing to be at risk for preterm delivery. Lacking scientific evidence, many investigators have performed retrospective analyses regarding the effects of single-course versus multiple-course antenatal corticosteroids.

The NIH consensus panel reconvened in 2000 and concluded that studies regarding repeated courses of corticosteroids are suggestive of possible benefits, especially in reduction of RDS, however, design flaws limit their validity.

The more recent publication from Caughey and Parer examined the literature for evidence regarding a dose response of the benefits and detriments of antenatal corticosteroids. Based on their complex mathematical analysis they recommend all fetus' between 24 and 34 weeks' gestation at risk for preterm delivery should be given a first course of ANC. If the risk of preterm delivery persists the next course should be given 2 weeks later, for a maximum of two courses. Consistent with all previous articles, the call for a well designed randomized, controlled trial is made.

Eligibility criteria: Inclusion Criteria:

* 25 to 32 6/7 weeks gestation
* Singleton or twin gestation
* Received 1st course of betamethasone prior to 30 weeks' gestation
* Began 1st course of betamethasone at least 14 days prior to randomization
* Risk of delivery in next 7 days due to either maternal or fetal complication (e.g. preterm labor, severe preeclampsia, IUGR, etc.)
* Intact membranes

Exclusion Criteria:

* Known major fetal anomalies (eg: anencephaly, renal agenesis etc...)
* High order multiple gestation (triplets or higher)
* Cervical dilation \> 5 cm
* Clinical chorioamnionitis prior to initiation of second course (two or more of the following; antepartum temperature \> 38ºC (100.4ºF), uterine tenderness, foul smelling vaginal discharge or amniotic fluid, maternal tachycardia (\>100beats/min), fetal tachycardia (\>160 beats/min), or white blood cell count \>20x109/L.define)
* Ruptured membranes prior to initiation of second course of betamethasone
* Already receiving corticosteroids for other conditions (e.g. Lupus, asthma)
* Maternal condition contraindicating the use of steroids (e.g. HIV, active Tuberculosis)
* Participation in conflicting study

Primary outcomes:
measure: Composite Neonatal Morbidity < 34 Weeks Gestation at Time of Birth.
timeFrame: From birth to 28 days of life
Secondary outcomes:
measure: Gestational Age at (@) Delivery
timeFrame: gestational age at delivery in weeks of gestation
measure: Neonatal Birth Weight Reported in Grams
timeFrame: At time of Birth
measure: Interuterine Growth Restriction (IUGR) or Small for Gestational Age(SGA)in Babies Delivering at < 34 Weeks Gestation.
timeFrame: Measured at birth.
measure: Neonatal Head Circumference Taken at Time of Birth.
timeFrame: Birth
measure: Number of Babies Who Required Ventilatory Support Within the First 28 Days of Life.
timeFrame: birth to 28 days of life
measure: Number of Neonates Who Required Surfactant Therapy After Birth.
timeFrame: Birth to 28 days of life
measure: Number of Neonates With Pneumothorax
timeFrame: birth to 28 days of life
measure: Maternal Infectious Morbidity.
timeFrame: Up to 28 days after giving birth
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Desert Good Samaritan Hospital
state: Arizona
city: Phoenix
country: United States
facility: Banner Good Sammaritan Hospital
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: Laguna Hills
country: United States
facility: Saddleback Memorial Medical Center
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Orange
country: United States
facility: University of Sourthern California-Irvine Medical Center
state: California
city: San Jose
country: United States
facility: Good Samaritan Hospital
state: California
city: Denver
country: United States
facility: Swedish Medical Center
state: Colorado
city: Denver
country: United States
facility: Presbyterian/St Luke's Hospital
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Lonetree
country: United States
facility: Skyridge Medical Center
state: Colorado
city: Des Moines
country: United States
facility: Mercy Medical Center
state: Iowa
city: Boston
country: United States
facility: Tufts-New England Medical Center
state: Massachusetts
city: Kansas City
country: United States
facility: Saint Luke's Hospital, Kansas City
state: Missouri
city: Springfield,
country: United States
facility: Saint John's Regional Health Center
state: Missouri
city: Las Vegas
country: United States
facility: University Med. Ctr. of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Sunrise Medical Center
state: Nevada
city: Chattanooga
country: United States
facility: Erlanger Medical Center
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Kirkland
country: United States
facility: Evergreen Hospital
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: Obstetrix Medical Group, Inc.
name: Kimberly Maurel, RN, MSN, CNS
role: STUDY_DIRECTOR
References:
citation: Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994 Feb 28-Mar 2;12(2):1-24.
citation: Vermillion ST, Soper DE, Newman RB. Is betamethasone effective longer than 7 days after treatment? Obstet Gynecol. 2001 Apr;97(4):491-3. doi: 10.1016/s0029-7844(00)01178-9.
citation: Antenatal corticosteroids revisited: repeat courses. NIH Consens Statement. 2000 Aug 17-18;17(2):1-18.
citation: Guinn DA, Atkinson MW, Sullivan L, Lee M, MacGregor S, Parilla BV, Davies J, Hanlon-Lundberg K, Simpson L, Stone J, Wing D, Ogasawara K, Muraskas J. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial. JAMA. 2001 Oct 3;286(13):1581-7. doi: 10.1001/jama.286.13.1581.
citation: Caughey AB, Parer JT. Recommendations for repeat courses of antenatal corticosteroids: a decision analysis. Am J Obstet Gynecol. 2002 Jun;186(6):1221-6; discussion 1226-9. doi: 10.1067/mob.2002.123742.