A Randomized Trial Comparing the Impact of One Versus Two Courses of Antenatal Steroids (ACS) on Neonatal Outcome

Preterm Delivery Clinical Trial

— ACS  

Official title:

A Randomized Double-Blinded Study Comparing the Impact of One Versus Two Courses of Antenatal Steroids on Neonatal Outcome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00201643
• Other study ID #: OBX0001
• Secondary ID: OBX0001
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2005
• Last updated: December 17, 2014
• Start date: November 2003
• Est. completion date: February 2008

Study information

• Verified date: December 2014
• Source: Mednax Center for Research, Education and Quality
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 437
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Premature Birth
• Preterm Delivery

Intervention

Drug:
• Betamethasone or Dexamethasone (2nd course of ACS)
Course of Betamethasone or Dexamethasone
• Placebo
Course of Placebo (NS)

Locations

Country	Name	City	State
United States	Tufts-New England Medical Center	Boston	Massachusetts
United States	Erlanger Medical Center	Chattanooga	Tennessee
United States	Presbyterian/St Luke's Hospital	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	Swedish Medical Center	Denver	Colorado
United States	Mercy Medical Center	Des Moines	Iowa
United States	Saint Luke's Hospital, Kansas City	Kansas City	Missouri
United States	Evergreen Hospital	Kirkland	Washington
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Saddleback Memorial Medical Center	Laguna Hills	California
United States	Sunrise Medical Center	Las Vegas	Nevada
United States	University Med. Ctr. of Southern Nevada	Las Vegas	Nevada
United States	Skyridge Medical Center	Lonetree	Colorado
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Desert Good Samaritan Hospital	Mesa	Arizona
United States	University of Sourthern California-Irvine Medical Center	Orange	California
United States	Banner Good Sammaritan Hospital	Phoenix	Arizona
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Good Samaritan Hospital	San Jose	California
United States	Swedish Medical Center	Seattle	Washington
United States	Saint John's Regional Health Center	Springfield,	Missouri
United States	Tucson Medical Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Obstetrix Medical Group

Country where clinical trial is conducted

United States, 

References & Publications (5)

Antenatal corticosteroids revisited: repeat courses. NIH Consens Statement. 2000 Aug 17-18;17(2):1-18. — View 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. — View Citation

Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994 Feb 28-Mar 2;12(2):1-24. Review. — View 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. — View Citation

Vermillion ST, Soper DE, Newman RB. Is betamethasone effective longer than 7 days after treatment? Obstet Gynecol. 2001 Apr;97(4):491-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Neonatal Morbidity < 34 Weeks Gestation at Time of Birth.	This outcome measured the total number of neonates with Composite Neonatal morbidity who delivered at < 34 weeks gestation. Composite Morbidity consisted of respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death	From birth to 28 days of life	Yes
Secondary	Gestational Age at (@) Delivery	Reported the average/mean Neonatal gestational age (GA) (reported in weeks of pregnancy) at the time of birth for both groups (ACS vs. Placebo).	gestational age at delivery in weeks of gestation	Yes
Secondary	Neonatal Birth Weight Reported in Grams	Measured mean Birth weights of Neonates in each arm as reported in grams on the birth record.	At time of Birth	Yes
Secondary	Interuterine Growth Restriction (IUGR) or Small for Gestational Age(SGA)in Babies Delivering at < 34 Weeks Gestation.	Noted as the total number of Neonates delivering at < 34 weeks gestation for which their weights fell within the 10th percentile at time of birth.	Measured at birth.	Yes
Secondary	Neonatal Head Circumference Taken at Time of Birth.	Reported as the average of all neonatal head circumferences (HC) taken at time of birth in each group.	Birth	Yes
Secondary	Number of Babies Who Required Ventilatory Support Within the First 28 Days of Life.	The number of babies who required ventilatory support within the first 28 days of life. Equal to or great than 12 hours was considered one day.	birth to 28 days of life	Yes
Secondary	Number of Neonates Who Required Surfactant Therapy After Birth.	The Number of neonates who required surfactant therapy within the first 28 days after birth.	Birth to 28 days of life	Yes
Secondary	Number of Neonates With Pneumothorax	Total number of neonates with pneumothorax diagnosed postpartum.	birth to 28 days of life	Yes
Secondary	Maternal Infectious Morbidity.	Total number of Mothers having Maternal infectious morbidity (e.g. endometritis & maternal sepsis) noted from birth through 28 days after birth	Up to 28 days after giving birth	Yes

External Links

•   Protocols' home page on the sponsor's Web site. Click on Protocols and then click the ACS Protocol for more information about this study.