Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial

This study is currently recruiting participants.
Verified November 2013 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01222247
First received: October 14, 2010
Last updated: November 15, 2013
Last verified: November 2013

October 14, 2010
November 15, 2013
October 2010
October 2014   (final data collection date for primary outcome measure)
Composite Outcome [ Time Frame: 72 hours of life ] [ Designated as safety issue: No ]
Need for respiratory support: Continuous positive airway pressure (CPAP) or humidified high-flow nasal cannula (HHFNC) for greater than or equal to 2 hours or more in the first 72 hours, or fraction of inspired oxygen (FiO2) greater than or equal to 0.30 for 4 hours or more in the first 72 hours, or mechanical ventilation in the first 72 hours, or Extracorporeal membrane oxygenation (ECMO) Stillbirth, or neonatal death less than 72 hours of age
Composite Outcome [ Time Frame: 72 hours of life ] [ Designated as safety issue: No ]
Need for respiratory support: Continuous positive airway pressure (CPAP) or humidified high-flow nasal cannula (HHFNC) for greater than or equal to 2 hours or more in the first 72 hours, or FiO2 greater than or equal to 0.30 for 4 hours or more in the first 72 hours, or mechanical ventilation in the first 72 hours, or Extracorporeal membrane oxygenation (ECMO) Stillbirth, or neonatal death less than 72 hours of age
Complete list of historical versions of study NCT01222247 on ClinicalTrials.gov Archive Site
  • Maternal outcomes [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Chorioamnionitis, Postpartum endomyometritis, delivery prior to steroids completion, time in hours from initial dose to delivery, length of labor, mode of delivery, indication for delivery, length of stay
  • Neonatal morbidity / mortality [ Time Frame: 72 hours of life ] [ Designated as safety issue: No ]
    Major respiratory morbidity: Continuous positive airway pressure (CPAP) or humidified high-flow nasal cannula (HHFNC) for greater than or equal to 12 hours or more in the first 72 hours, or FiO2 greater than or equal to 0.30 for 24 hours or more in the first 72 hours, or mechanical ventilation in the first 72 hours, or Extracorporeal membrane oxygenation (ECMO) Stillbirth or neonatal death less than 72 hours of age
  • Respiratory Distress Syndrome [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Respiratory distress with an oxygen requirement and a chest x-ray that shows hypoaeration and reticulogranular infiltrates
  • Neonatal composite [ Time Frame: 72 hours of life ] [ Designated as safety issue: No ]
    Transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), and apnea
  • Need for immediate resuscitation after birth [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Surfactant use [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Chronic lung disease (BPD) [ Time Frame: 28 days of life ] [ Designated as safety issue: No ]
    Infants requiring oxygen at 28 days of life
  • Necrotizing enterocolitis (NEC) [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Defined as modified Bell Stage 2 or 3. Stage 2: Clinical signs and symptoms with pneumatosis intestinalis on radiographs. Stage 3: Advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation.
  • Morbidity composite [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    A composite endpoint of morbidities known to be affected by steroid administration will also be evaluated. Specifically, this composite will include RDS, intraventricular hemorrhage (IVH), and NEC
  • Birth weight [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Hypoglycemia [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Glucose < 40 mg%
  • Hyperbilirubinemia [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Peak total bilirubin of at least 15 mg% or the use of phototherapy.
  • Feeding difficulty [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Inability to take all feeds (po), i.e. requiring gavage feeds or IV supplementation. In addition, time to first feed (po) will be recorded.
  • Hypothermia [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Rectal temperature < 36 C
  • Neonatal infectious morbidity [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    • Sepsis (within 72hrs and > 72 hrs after birth) OR
    • Suspected sepsis OR
    • Pneumonia
  • Seizures / encephalopathy [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Length of hospital stay [ Time Frame: Discharge from hospital ] [ Designated as safety issue: No ]
    Includes need for NICU or intermediate care admission and length of stay if admitted
  • Number of and reason for infant re-hospitalizations, ER visits or unanticipated visits to the primary care pediatrician / specialist [ Time Frame: 3 and 6 months of age ] [ Designated as safety issue: No ]
  • Maternal outcomes [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Chorioamnionitis, Postpartum endomyometritis, delivery prior to steroids completion, time in hours from initial dose to delivery, length of labor, mode of delivery, indication for delivery, length of stay
  • Neonatal morbidity / mortality [ Time Frame: 72 hours of life ] [ Designated as safety issue: No ]
    Major respiratory morbidity: Continuous positive airway pressure (CPAP) or humidified high-flow nasal cannula (HHFNC) for greater than or equal to 12 hours or more in the first 72 hours, or FiO2 greater than or equal to 0.30 for 24 hours or more in the first 72 hours, or mechanical ventilation in the first 72 hours, or Extracorporeal membrane oxygenation (ECMO) Stillbirth or neonatal death less than 72 hours of age
  • Respiratory Distress Syndrome [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Respiratory distress with an oxygen requirement and a chest x-ray that shows hypoaeration and reticulogranular infiltrates
  • Neonatal composite [ Time Frame: 72 hours of life ] [ Designated as safety issue: No ]
    Transient tachypnea of the newborn (TTN), RDS, and apnea
  • Need for immediate resuscitation after birth [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Surfactant use [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Chronic lung disease (BPD) [ Time Frame: 28 days of life ] [ Designated as safety issue: No ]
    Infants requiring oxygen at 28 days of life
  • Necrotizing enterocolitis (NEC) [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Defined as modified Bell Stage 2 or 3. Stage 2: Clinical signs and symptoms with pneumatosis intestinalis on radiographs. Stage 3: Advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation.
  • Morbidity composite [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    A composite endpoint of morbidities known to be affected by steroid administration will also be evaluated. Specifically, this composite will include RDS, IVH, and NEC
  • Birth weight [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Hypoglycemia [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Glucose < 40 mg%
  • Hyperbilirubinemia [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Peak total bilirubin of at least 15 mg% or the use of phototherapy.
  • Feeding difficulty [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Inability to take all feeds (po), i.e. requiring gavage feeds or IV supplementation. In addition, time to first feed (po) will be recorded.
  • Hypothermia [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Rectal temperature < 36 C
  • Neonatal infectious morbidity [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    • Sepsis (within 72hrs and > 72 hrs after birth) OR
    • Suspected sepsis OR
    • Pneumonia
  • Seizures / encephalopathy [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Length of hospital stay [ Time Frame: Discharge from hospital ] [ Designated as safety issue: No ]
    Includes need for NICU or intermediate care admission and length of stay if admitted
  • Number of and reason for infant re-hospitalizations, ER visits or unanticipated visits to the primary care pediatrician / specialist [ Time Frame: 3 and 6 months of age ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial
Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial

Infants born between 34 and 36 weeks of gestation, known as 'late preterm', are more likely to be admitted to a special care nursery, and more likely to suffer respiratory complications than infants born at term. The use of antenatal corticosteroids has been shown to improve lung function in very premature infants, but has not been evaluated in those likely to deliver in the late preterm period.

This research study will attempt to answer the following primary research question: Do steroids, compared to no steroids, decrease babies' need for oxygen support when given to pregnant women at least 12 to 24 hours before they deliver at 34 weeks to 36 weeks gestation? The research study will also collect information on whether steroids improve the chances that the baby will not get sick from other causes.

Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial:

The rate of preterm birth has steadily increased in the United States over the past 10 years. This increase is driven in part by the rising rate of late preterm birth, defined as those births occurring between 34 and 36 weeks. Late preterm infants experience a higher rate of readmission than their term counterparts, and these infants are more likely to suffer complications such as respiratory distress, kernicterus, feeding difficulties, and hypoglycemia. Late preterm infants also have a higher mortality for all causes when compared to term infants. The use of antenatal corticosteroids has been shown to be beneficial in women at risk for preterm delivery prior to 34 weeks but has not been evaluated in those likely to deliver in the late preterm period. If shown to reduce the need for respiratory support and thus to decrease the rate of special care nursery admissions and improve short-term outcomes, the public health and economic impact will be considerate.

This protocol describes a randomized placebo controlled trial to evaluate whether antenatal corticosteroids can decrease the rate of neonatal respiratory support, thus decreasing the rate of neonatal intensive care unit (NICU) admissions and improving short-term outcomes in the late preterm infant.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Pregnancy
  • Respiratory Distress
  • Pregnancy Outcome
Drug: Corticosteroid

The active study drug, betamethasone, trade name Celestone Soluspan® manufactured by Schering Plough.

3 mg per ml betamethasone sodium phosphate 3 mg per milliliter betamethasone acetate The first dose of study drug medication will be administered at randomization as 2 ml injection; the next dose of 2 ml will be administered 24 hours later.

Other Name: Celestone Soluspan
  • Active Comparator: Corticosteroid
    Intervention: Drug: Corticosteroid
  • Placebo Comparator: Placebo
    Intervention: Drug: Corticosteroid

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
2800
December 2014
October 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

Singleton Pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 14,0 weeks by project gestational age is acceptable

Gestational age at randomization between 34,0weeks and 36,5 weeks confirmed by study criteria

High probability of delivery in the late preterm period (any one of the following):

  • Membrane rupture as defined by the study criteria.

or

  • Preterm labor with intact membranes. Preterm labor is defined as at least 6 regular uterine contractions in an observation period of no more than 60 minutes and at least one of the following: cervix greater than or equal to 3cm dilated or 80% effaced

or

  • Planned delivery by induction of labor or cesarean section in no less than 24 hours and no more than 7 days, as deemed necessary by the provider. An induction must be scheduled to start by 36,5 weeks at the latest, whereas a cesarean delivery must be scheduled by 36,6 weeks at the latest. Therefore the latest gestational age for randomization is 36,4 weeks for a planned induction. The planned delivery may be for any indication, such as the following: prior myomectomy, prior classical cesarean, intrauterine growth restriction (IUGR), oligohydramnios, preeclampsia, nonreassuring fetal heart rate tracing warranting delivery, abruption, placenta previa

Exclusion Criteria:

  • Rupture of Membranes (ROM) does not satisfy protocol criteria - exclude if the patient being evaluated for Preterm Premature Rupture of Membranes (pPROM) does not have preterm labor or planned delivery and does not satisfy the spontaneous membrane rupture criteria (any 2 of: positive Nitrazine test, pooling of fluid in the vaginal vault test or ferning of vaginal fluid; or indigo carmine pooling in the vagina after amnioinfusion; or visible leakage of amniotic fluid from the cervix)
  • Preterm labor does not satisfy protocol criteria - exclude if patient has intact membranes with no delivery planned and contractions are more than 10 minutes apart or if the cervix is both less than 3cm dilated and less than 80% effaced
  • Fetal death / major fetal anomaly / fetus non-viable - exclude if the patient has a major fetal anomaly or the fetus is not viable
  • Delivery expected < 12 hours after randomization - this includes 1) ruptured membranes with cervical dilation ≥ 3cm or more than 6 contractions per hour unless pitocin is deferred for at least 12 hours 2) evidence of non-reassuring fetal status requiring immediate delivery 3) chorio-amnionitis 4) Cervical dilation ≥ 8 cm
  • Prior corticosteroids for fetal lung maturity - exclude if patient was given corticosteroids for fetal lung maturity before 34 weeks
  • Systemic corticosteroids for other indications - exclude if patient was given systemic corticosteroids for indication other than fetal lung maturity
  • No ultrasound < 20 weeks for unsure last menstrual period (LMP). If the patient has an unsure LMP but she had no dating ultrasound before 20 weeks by ultrasound parameters, she is excluded.
  • No ultrasound < 24 weeks for sure LMP. If the patient has an sure LMP but she had no dating ultrasound before 24 weeks by ultrasound parameters, she is excluded
  • Cervical dilation ≥ 8 cm
  • Project gestational age < 34,0 weeks or ≥ 36,6 weeks
  • Delivery planned at project gestational age ≥ 36,6 weeks
  • Known congenital malformation
  • Fetal reduction/loss ≥ 14 weeks - exclude if the singleton pregnancy is due to reduction or fetal loss from a twin pregnancy at greater or equal to 14 weeks
  • Gestational diabetes
  • Pre-gestational diabetes - exclude if the patient was on medication (insulin, glyburide) prior to pregnancy
  • Maternal contraindication to betamethasone - exclude if the patient has a known contraindication to betamethasone
  • Chorioamnionitis - exclude if patient is diagnosed with chorioamnionitis
  • Physician planning to give steroids - exclude if patient's physician is planning to give her steroids
  • Physician refusal for other reasons - exclude if patient's physician refuses to allow the patient to participate in the study
  • Refusal to sign medical record release
  • Participation in conflicting study / this study before - exclude if the patient is participating in an antenatal study in which the clinical status or intervention may influence neonatal respiratory outcome, or if she was previously enrolled in this study
  • Multifetal gestation. Exclude if current multifetal gestation or a single gestation resulting from a reduction of a multiple of higher order than twins
  • Delivery at a non-participating hospital
  • Gestational age 36,0 or more and quota already reached.
Female
Not Provided
Yes
Contact: Uma Reddy, MD, MPH 301-496-1074 uma.reddy@nih.gov
Contact: Elizabeth A Thom, PhD 301-881-9260
United States
 
NCT01222247
HL98354-HD36801-ALPS, U10HD021410, U10HD027869, U10HD027917, U10HD053118, U10HD027915, U10HD034116, U10HD034208, U10HD053097, U10HD040500, U10HD040485, U10HD040544, U10HD040545, U10HD040560, U10HD040512, U01HD036801, U01HL098354, U01HL098554
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Heart, Lung, and Blood Institute (NHLBI)
Study Director: Uma Reddy, MD, MPH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Elizabeth Thom, PhD George Washington University
Study Chair: Cynthia Gyamfi Bannerman, MD Columbia University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP