Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial (ALPS)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01222247|
Recruitment Status : Active, not recruiting
First Posted : October 18, 2010
Results First Posted : January 30, 2019
Last Update Posted : July 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Pregnancy Respiratory Distress Syndrome Pregnancy Outcomes Preterm Birth||Drug: Betamethasone Drug: Placebo||Phase 3|
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.
Two follow-up studies will be conducted concurrently. The first follow-up study will examine if the positive effects of betamethasone on lung function will persist in children at 6 years of age of mothers randomized to betamethasone with an expected late preterm delivery. Neonatal respiratory morbidity is associated with an increased risk of adverse childhood respiratory disease. Thus it is quite plausible that the effect of betamethasone, in reducing neonatal morbidity, particularly TTN, will translate into improved respiratory morbidity in early childhood.The primary outcome is childhood respiratory disease defined by a composite outcome of abnormal pulmonary function test (PFT) measured by spirometry, physician diagnosis of asthma, or other respiratory illnesses with medication.
The second follow-up study will examine whether late preterm antenatal betamethasone treatment is associated with long-term neurocognitive functioning, and whether there are any long-term consequences of what is believed to be transient neonatal hypoglycemia. Cognitive function will be measured by the Differential Ability Scales 2nd Edition (DAS-II) core components of the general conceptual ability (GCA) that includes verbal ability, non-verbal reasoning ability and spatial ability. The primary outcome is defined as a GCA score of <85 (1 standard deviation below the mean) at 6 years of age or greater.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2831 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||March 2015|
|Estimated Study Completion Date :||May 2022|
Active Comparator: Betamethasone
A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
The active study drug, betamethasone. 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: Corticosteroid
Placebo Comparator: Placebo
A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart
Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.
- Neonatal Composite Outcome [ Time Frame: 72 hours of life ]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
- Number of Neonates With Severe Respiratory Complication, [ Time Frame: 72 hours of life ]A severe respiratory complication was defined as any of the following occurrences within 72 hours after birth: CPAP or high-flow nasal cannula for at least 12 hours, supplemental oxygen with a fraction of inspired oxygen of 0.30 or more for at least 24 hours, mechanical ventilation, stillbirth or neonatal death, or the need for ECMO. Except for the duration of CPAP or high-flow nasal cannula and the duration of a fraction of inspired oxygen of 0.30 or more, the criteria for a severe respiratory complication overlap with those of the primary outcome.
- Neonates Needing Immediate Resuscitation After Birth [ Time Frame: Within the first 30 minutes of birth ]Need for resuscitation after birth: any intervention in the first 30 minutes other than blow-by oxygen
- Number of Neonates With Respiratory Distress Syndrome [ Time Frame: Delivery ]Respiratory distress defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis) with an oxygen requirement and a chest x-ray that shows hypoaeration and reticulogranular infiltrates
- Number of Neonates With Transient Tachypnea of the Newborn [ Time Frame: by 72 hours after delivery ]TTN is defined as signs of respiratory distress, specifically tachypnea, that are resolved by 72 hours of age. TTN may be diagnosed in the absence of a chest X-ray or with a chest X-ray that is normal or shows signs of increased perihilar interstitial markings
- Number of Infants With Neonatal Apnea [ Time Frame: 72 hours of life ]Neonatal apnea with respiratory pauses of more than 20 seconds duration resulting in bradycardia or oxygen desaturation below baseline.
- Number of Infants withChronic Lung Disease / Bronchopulmonary Dysplasia (BPD) Requiring Supplemental Oxygen [ Time Frame: 28 days of life ]Infants requiring supplemental oxygen of more than 0.21 for the first 28 days of life
- Neonates With Pneumonia [ Time Frame: by 72 hours of life ]Neonatal pneumonia
- Number of Neonates Needing Surfactant Administration [ Time Frame: Delivery ]Administration of surfactant for neonatal respiratory treatment
- Neonatal Outcome Composite [ Time Frame: 72 hours of life ]Transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), and apnea
- Number of Neonates With Pulmonary Air Leak [ Time Frame: 72 hours post delivery ]Neonatal pulmonary air leak syndrome
- Neonatal Death After 72 Hours of Delivery [ Time Frame: 72 hours after delivery through hospital discharge up to 3 weeks ]Neonatal death after 72 hours of life but before hospital discharge.
- Birth Weight [ Time Frame: Delivery ]Weight in grams at delivery
- Birth Weight Less Than 10th Percentile [ Time Frame: Delivery ]Neonates whose birth weight is less than the 10th percentile at delivery
- Gestational Age at Delivery [ Time Frame: Delivery ]Number of neonates delivered at ≤ 34 weeks 6 days, between 35 weeks 0 days and 35 weeks 6 days, between 36 weeks 0 days and 36 weeks 6 days, between 37 weeks 0 days and 38 weeks 6 days, or on or after 39 weeks 0 days
- Number of Neonates With Necrotizing Enterocolitic (NEC) [ Time Frame: Delivery ]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.
- Number of Infants With Neonatal Sepsis [ Time Frame: Delivery ]Clinical suspicion of systemic infection with a positive blood, cerebral spinal fluid, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evience of cardiovascular collapse or an X-ray confirming infection.
- Number of Neonates With Intraventricular Hemorrhage [ Time Frame: Delivery ]Grade 3 or 4 Intraventricular Hemorrhage
- Neonatal Morbidity Composite [ Time Frame: Delivery ]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
- Number of Neonates With Hypoglycemia [ Time Frame: Delivery through hospital discharge up to 3 weeks ]Glucose < 40 mg per deciliter (2.2 mmol per liter) at any time
- Time Until First Neonatal Feeding [ Time Frame: Delivery to 36 hours post delivery ]Median length of time from delivery until the first neonatal feeding
- Neonatal Feeding Difficulty [ Time Frame: Delivery to 36 hours post delivery ]Inability of the neonate to take all feeds (po), i.e. requiring gavage feeds or IV supplementation.
- Neonatal Hyperbilirubinemia [ Time Frame: Delivery ]Peak total bilirubin of at least 15 mg% or the use of phototherapy.
- Number of Neonates With Hypothermia [ Time Frame: Delivery through discharge up to 3 weeks ]Rectal temperature < 36 C at any time
- Length of NICU or Nursery Stay [ Time Frame: Delivery through hospital discharge up to 3 weeks ]Includes need for NICU or intermediate care admission and length of stay if admitted. For analysis purposes, death before discharge is assigned maximum rank
- Median Length of Hospital Stay [ Time Frame: Duration of hospital stay following delivery up to 2 weeks ]Median length of maternal hospital stay following delivery
- Maternal Outcomes (Participant-based) [ Time Frame: Labor and delivery through 72 hours post partum ]Chorioamnionitis: clinical diagnosis and a body temperature of at least 100.4 degrees F., Endometritis: persistent postpartum temperature greater than 100.4 degrees F with uterine tenderness, cesarean delivery
- Hours From Randomization to Delivery [ Time Frame: Randomization through delivery ]Median interval of hours from randomization to delivery
- Median Length of Maternal Hospital Stay [ Time Frame: Delivery through hospital discharge ]Median length of maternal hospital stay in days
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01222247
|Study Director:||Menachem Miodovnik, MD||NICHD Project Scientist|
|Principal Investigator:||Rebecca Clifton, PhD||George Washington University|
|Study Chair:||Cynthia Gyamfi Bannerman, MD||Columbia University|