PregnancyPhase 3ALPSNCT01222247

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

A Phase 3 study testing Betamethasone in people with Pregnancy and Respiratory Distress Syndrome, run by The George Washington University Biostatistics Center at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Any age, women onlyHealthy volunteers can take part
Conditions the study is for: Pregnancy, Respiratory Distress Syndrome, Pregnancy Outcomes
What is being tested?: Betamethasone
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 2,831 participants
Where: 17 sitesUnited States
Study dates: Oct 2010to 31 Aug 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
Women only
Healthy volunteers accepted
Child, Adult, Older adult

Who may be able to join

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 34,0 weeks 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 occurrence of any two of the following: pooling of fluid in the vaginal vault, positive Nitrazine test, ferning of vaginal fluid, positive AmniSure test; or any one of the following: indigo carmine pooling in the vagina after amnioinfustion, visible leakage of amniotic fluid from the cervix
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 at least 75% 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

Who cannot join

Any prior antenatal corticosteroid course during the pregnancy because of potential contamination of the placebo group
Candidate for stress dose corticosteroids because of chronic steroid therapy to prevent suppression of adrenal gland, because of potential contamination of the placebo group
Twin gestation reduced to a singleton gestation at or after 14 weeks 0 days by project gestational age either spontaneously or therapeutically
Fetal demise, or known major fetal anomaly, including cardiac anomaly and hydrops
Maternal contraindication to betamethasone: hypersensitivity reaction to any components of the medication, idiopathic thromboycytopenic purpura, systemal fungal infection in case of exacerbation by betamethasone, use of amphotericin B due to the possibility of heart failure with concomitant betamethasone
Pre-gestational diabetes - exclude if the patient was on medication (insulin, glyburide) prior to pregnancy

Show all 12Show fewer

Delivery expected within 12 hours of randomization, because of insufficient time of corticosteroids to confer benefit, including any of the following:
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) B. Rupture of the membranes in the presence of more than 6 contractions per hour or cervical dilation of 3 cm or more, unless oxytocin was withheld for at least 12 hours (other induction agents allowed) C. Chorioamnionitis - exclude if patient is diagnosed with chorioamnionitis D. Cervical dilation ≥ 8 cm E. Evidence of non-reassuring fetal status requiring immediate delivery
Participation in another interventional study that influences neonatal morbidity and mortality
Participation in this trial in a previous pregnancy
Delivery at a non-network hospital
At 36, 0 weeks to 36, 5 weeks and quota for 36 weeks already met. To ensure there is an adequate proportion of women presenting at 34 to 35 weeks of gestation, enrollment will be restricted so that no more than 50% of the women in the trial present at 36 weeks.

Trial locations and contacts

17 sites in 1 country.

City, postcode or hospital

17 sites in 1 country

United States17 sites

University of Alabama - Birmingham
Birmingham, Alabama, 35233
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
Case Western Reserve University
Cleveland, Ohio, 44109
Ohio State University
Columbus, Ohio, 43210
University of Texas - Southwest
Dallas, Texas, 75235
University of Colorado
Denver, Colorado, 80045
Wayne State University
Detroit, Michigan, 48201
Duke University
Durham, North Carolina, 27710
University of Texas - Galveston
Galveston, Texas, 77555
University of Texas - Houston
Houston, Texas, 77030
Columbia University
New York, New York, 10032
University of Pittsburgh Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
Oregon Health & Science University
Portland, Oregon, 97239
Brown University
Providence, Rhode Island, 02905
University of Utah Medical Center
Salt Lake City, Utah, 84132
Stanford University
Stanford, California, 94305

Other trials in United States

About this study

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

Read the detailed description

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.

Conditions: Pregnancy, Respiratory Distress Syndrome, Pregnancy Outcomes, Preterm Birth
Being tested: Betamethasone, Placebo
Keywords: Betamethasone, Steroids, Perinatology, Late Preterm
Medical subject headings: Respiratory Distress Syndrome, Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BetamethasoneDrug
Also called Corticosteroid
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.
PlaceboDrug
Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Study groups in NCT01222247
Study group	Role	What they receive
Betamethasone	Active comparator	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart Receives: Drug: Betamethasone
Placebo	Placebo comparator	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Neonatal Composite Outcome
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
Measured: 72 hours of life

Secondary outcomes (28)

Number of Neonates With Severe Respiratory Complication,
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.
Measured: 72 hours of life
Neonates Needing Immediate Resuscitation After Birth
Need for resuscitation after birth: any intervention in the first 30 minutes other than blow-by oxygen
Measured: Within the first 30 minutes of birth
Number of Neonates With Respiratory Distress Syndrome
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
Measured: Delivery
Number of Neonates With Transient Tachypnea of the Newborn
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
Measured: by 72 hours after delivery
Number of Infants With Neonatal Apnea
Neonatal apnea with respiratory pauses of more than 20 seconds duration resulting in bradycardia or oxygen desaturation below baseline.
Measured: 72 hours of life
Number of Infants withChronic Lung Disease / Bronchopulmonary Dysplasia (BPD) Requiring Supplemental Oxygen
Infants requiring supplemental oxygen of more than 0.21 for the first 28 days of life
Measured: 28 days of life
Neonates With Pneumonia
Neonatal pneumonia
Measured: by 72 hours of life
Number of Neonates Needing Surfactant Administration
Administration of surfactant for neonatal respiratory treatment
Measured: Delivery
Neonatal Outcome Composite
Transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), and apnea
Measured: 72 hours of life
Number of Neonates With Pulmonary Air Leak
Neonatal pulmonary air leak syndrome
Measured: 72 hours post delivery
Neonatal Death After 72 Hours of Delivery
Neonatal death after 72 hours of life but before hospital discharge.
Measured: 72 hours after delivery through hospital discharge up to 3 weeks
Birth Weight
Weight in grams at delivery
Measured: Delivery
Birth Weight Less Than 10th Percentile
Neonates whose birth weight is less than the 10th percentile at delivery
Measured: Delivery
Gestational Age at 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
Measured: Delivery
Number of Neonates With Necrotizing Enterocolitic (NEC)
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.
Measured: Delivery
Number of Infants With Neonatal Sepsis
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.
Measured: Delivery
Number of Neonates With Intraventricular Hemorrhage
Grade 3 or 4 Intraventricular Hemorrhage
Measured: Delivery
Neonatal Morbidity Composite
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
Measured: Delivery
Number of Neonates With Hypoglycemia
Glucose < 40 mg per deciliter (2.2 mmol per liter) at any time
Measured: Delivery through hospital discharge up to 3 weeks
Time Until First Neonatal Feeding
Median length of time from delivery until the first neonatal feeding
Measured: Delivery to 36 hours post delivery
Neonatal Feeding Difficulty
Inability of the neonate to take all feeds (po), i.e. requiring gavage feeds or IV supplementation.
Measured: Delivery to 36 hours post delivery
Neonatal Hyperbilirubinemia
Peak total bilirubin of at least 15 mg% or the use of phototherapy.
Measured: Delivery
Number of Neonates With Hypothermia
Rectal temperature < 36 C at any time
Measured: Delivery through discharge up to 3 weeks
Length of NICU or Nursery Stay
Includes need for NICU or intermediate care admission and length of stay if admitted. For analysis purposes, death before discharge is assigned maximum rank
Measured: Delivery through hospital discharge up to 3 weeks
Median Length of Hospital Stay
Median length of maternal hospital stay following delivery
Measured: Duration of hospital stay following delivery up to 2 weeks
Maternal Outcomes (Participant-based)
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
Measured: Labor and delivery through 72 hours post partum
Hours From Randomization to Delivery
Median interval of hours from randomization to delivery
Measured: Randomization through delivery
Median Length of Maternal Hospital Stay
Median length of maternal hospital stay in days
Measured: Delivery through hospital discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 201031 Aug 2022

First posted18 Oct 2010 (estimated)
Study startOct 2010
Primary completionMar 2015
Study completion31 Aug 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (26)Papers the sponsor has linked to this study.
Other trials for PregnancyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 2,831 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01222247
Sponsor's protocol ID: HL98354-HD36801-ALPS
Other IDs: U10HD021410, U10HD027869, U10HD027917, U10HD053118, U10HD027915, U10HD034116, U10HD034208, U10HD053097
Acronym: ALPS
Status last verified: Mar 2023
First submitted: 14 Oct 2010
Last updated: 28 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Data will be shared after completion and publication of the main analyses per NIH policy. Requests can be sent to mfmudatasets@bsc.gwu.edu.

Publications

Davidoff MJ, Dias T, Damus K, Russell R, Bettegowda VR, Dolan S, Schwarz RH, Green NS, Petrini J. Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to 2002. Semin Perinatol. 2006 Feb;30(1):8-15. doi: 10.1053/j.semperi.2006.01.009.
PubMed 16549207
Raju TN, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics. 2006 Sep;118(3):1207-14. doi: 10.1542/peds.2006-0018.
PubMed 16951017
Escobar GJ, Clark RH, Greene JD. Short-term outcomes of infants born at 35 and 36 weeks gestation: we need to ask more questions. Semin Perinatol. 2006 Feb;30(1):28-33. doi: 10.1053/j.semperi.2006.01.005.
PubMed 16549211
Hamilton BE, Ventura SJ, Martin JA, and Sutton PD. Preliminary births for 2004. Health E-stats. Hyattsville, MD: National Center for Health Statistics. Released October 28, 2005.
Buus-Frank ME. The great imposter. Adv Neonatal Care. 2005 Oct;5(5):233-6. doi: 10.1016/j.adnc.2005.08.012. No abstract available.
PubMed 16202965
Hoyert DL, Mathews TJ, Menacker F, Strobino DM, Guyer B. Annual summary of vital statistics: 2004. Pediatrics. 2006 Jan;117(1):168-83. doi: 10.1542/peds.2005-2587.
PubMed 16396875
Dudell GG, Jain L. Hypoxic respiratory failure in the late preterm infant. Clin Perinatol. 2006 Dec;33(4):803-30; abstract viii-ix. doi: 10.1016/j.clp.2006.09.006.
PubMed 17148006
Laptook A, Jackson GL. Cold stress and hypoglycemia in the late preterm ("near-term") infant: impact on nursery of admission. Semin Perinatol. 2006 Feb;30(1):24-7. doi: 10.1053/j.semperi.2006.01.014.
PubMed 16549210
Neu J. Gastrointestinal maturation and feeding. Semin Perinatol. 2006 Apr;30(2):77-80. doi: 10.1053/j.semperi.2006.02.007.
PubMed 16731281
Bhutani VK, Johnson L. Kernicterus in late preterm infants cared for as term healthy infants. Semin Perinatol. 2006 Apr;30(2):89-97. doi: 10.1053/j.semperi.2006.04.001.
PubMed 16731283
Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008 Jul 17;359(3):262-73. doi: 10.1056/NEJMoa0706475.
PubMed 18635431
McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008 Jan;111(1):35-41. doi: 10.1097/01.AOG.0000297311.33046.73.
PubMed 18165390
Kramer MS, Demissie K, Yang H, Platt RW, Sauve R, Liston R. The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. JAMA. 2000 Aug 16;284(7):843-9. doi: 10.1001/jama.284.7.843.
PubMed 10938173
Gray RF, Indurkhya A, McCormick MC. Prevalence, stability, and predictors of clinically significant behavior problems in low birth weight children at 3, 5, and 8 years of age. Pediatrics. 2004 Sep;114(3):736-43. doi: 10.1542/peds.2003-1150-L.
PubMed 15342847
Linnet KM, Wisborg K, Agerbo E, Secher NJ, Thomsen PH, Henriksen TB. Gestational age, birth weight, and the risk of hyperkinetic disorder. Arch Dis Child. 2006 Aug;91(8):655-60. doi: 10.1136/adc.2005.088872. Epub 2006 Jun 5.
PubMed 16754656

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial
ClinicalTrials.gov ID: NCT01222247
Acronym / sponsor ID: ALPS / HL98354-HD36801-ALPS
Conditions: Pregnancy, Respiratory Distress Syndrome, Pregnancy Outcomes, Preterm Birth
Keywords: Betamethasone, Steroids, Perinatology, Late Preterm
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 2,831 participants (actual)
Lead sponsor: The George Washington University Biostatistics CenterUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: Oct 2010 (actual)
Primary completion: Mar 2015 (actual)
Study completion: 31 Aug 2022 (actual)
First posted: 18 Oct 2010 (estimated)
Results: Posted 30 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Betamethasone	Active comparator	Drug: BetamethasoneA course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
Placebo	Placebo comparator	Drug: PlaceboA similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart

Who may qualify

Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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 34,0 weeks and 36,5 weeks confirmed by study criteria
Membrane rupture as defined by the occurrence of any two of the following: pooling of fluid in the vaginal vault, positive Nitrazine test, ferning of vaginal fluid, positive AmniSure test; or any one of the following: indigo carmine pooling in the vagina after amnioinfustion, visible leakage of amniotic fluid from the cervix
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 at least 75% effaced

Key exclusion criteria (12 listed)

Any prior antenatal corticosteroid course during the pregnancy because of potential contamination of the placebo group
Candidate for stress dose corticosteroids because of chronic steroid therapy to prevent suppression of adrenal gland, because of potential contamination of the placebo group
Twin gestation reduced to a singleton gestation at or after 14 weeks 0 days by project gestational age either spontaneously or therapeutically
Fetal demise, or known major fetal anomaly, including cardiac anomaly and hydrops
Maternal contraindication to betamethasone: hypersensitivity reaction to any components of the medication, idiopathic thromboycytopenic purpura, systemal fungal infection in case of exacerbation by betamethasone, use of amphotericin B due to the possibility of heart failure with concomitant betamethasone

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BetamethasoneAlso: CorticosteroidThe 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.	Drug	Betamethasone
PlaceboSimilar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.	Drug	Placebo

Primary outcome

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

28 secondary outcomes

Number of Neonates With Severe Respiratory Complication,
Time frame: 72 hours of life
Neonates Needing Immediate Resuscitation After Birth
Time frame: Within the first 30 minutes of birth
Number of Neonates With Respiratory Distress Syndrome
Time frame: Delivery
Number of Neonates With Transient Tachypnea of the Newborn
Time frame: by 72 hours after delivery
Number of Infants With Neonatal Apnea
Time frame: 72 hours of life
Number of Infants withChronic Lung Disease / Bronchopulmonary Dysplasia (BPD) Requiring Supplemental Oxygen
Time frame: 28 days of life
Neonates With Pneumonia
Time frame: by 72 hours of life
Number of Neonates Needing Surfactant Administration
Time frame: Delivery
Neonatal Outcome Composite
Time frame: 72 hours of life
Number of Neonates With Pulmonary Air Leak
Time frame: 72 hours post delivery
Neonatal Death After 72 Hours of Delivery
Time frame: 72 hours after delivery through hospital discharge up to 3 weeks
Birth Weight
Time frame: Delivery
Birth Weight Less Than 10th Percentile
Time frame: Delivery
Gestational Age at Delivery
Time frame: Delivery
Number of Neonates With Necrotizing Enterocolitic (NEC)
Time frame: Delivery
Number of Infants With Neonatal Sepsis
Time frame: Delivery
Number of Neonates With Intraventricular Hemorrhage
Time frame: Delivery
Neonatal Morbidity Composite
Time frame: Delivery
Number of Neonates With Hypoglycemia
Time frame: Delivery through hospital discharge up to 3 weeks
Time Until First Neonatal Feeding
Time frame: Delivery to 36 hours post delivery
Neonatal Feeding Difficulty
Time frame: Delivery to 36 hours post delivery
Neonatal Hyperbilirubinemia
Time frame: Delivery
Number of Neonates With Hypothermia
Time frame: Delivery through discharge up to 3 weeks
Length of NICU or Nursery Stay
Time frame: Delivery through hospital discharge up to 3 weeks
Median Length of Hospital Stay
Time frame: Duration of hospital stay following delivery up to 2 weeks
Maternal Outcomes (Participant-based)
Time frame: Labor and delivery through 72 hours post partum
Hours From Randomization to Delivery
Time frame: Randomization through delivery
Median Length of Maternal Hospital Stay
Time frame: Delivery through hospital discharge

Results and safety

Results posted to the registry on 30 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Betamethasone	1,429	1,427
Placebo	1,402	1,400

Primary outcome: Neonatal Composite Outcome

Time frame: 72 hours of life. Count of participants. Unit: Participants

Measure	Betamethasone n = 1427	Placebo n = 1400
Primary Outcome Composite	165	202
CPAP or high-flow cannula ≥2 continuous hrs	145	184
Fraction of inspired O2 of ≥0.30 for ≥4 cont hrs	48	61
Mechanical ventilation	34	43
Extracorporeal membrane oxygenation (ECMO)	0	0
Stillbirth or neonatal death ≤72 hr after birth	0	0

Betamethasone vs Placebo: Risk Ratio (RR): 0.80 (95% CI 0.66 to 0.97), p = 0.02, Chi-squared
Betamethasone vs Placebo: Risk Ratio (RR): 0.77 (95% CI 0.63 to 0.95), p = 0.01, Chi-squared
Betamethasone vs Placebo: Risk Ratio (RR): 0.77 (95% CI 0.53 to 1.12), p = 0.17, Chi-squared

Population analysed: The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

28 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the time of randomization into the study through 72 hours after delivery.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Betamethasone	13 of 1,429 (0.9%)	223 of 1,428 (15.6%)	2 of 1,429
Placebo	12 of 1,402 (0.9%)	352 of 1,397 (25.2%)	0 of 1,402

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16549207Davidoff MJ, Dias T, Damus K, Russell R, Bettegowda VR, Dolan S, Schwarz RH, Green NS, Petrini J. Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to 2002. Semin Perinatol. 2006 Feb;30(1):8-15. doi: 10.1053/j.semperi.2006.01.009.
Background: PubMed 16951017Raju TN, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics. 2006 Sep;118(3):1207-14. doi: 10.1542/peds.2006-0018.
Background: PubMed 16549211Escobar GJ, Clark RH, Greene JD. Short-term outcomes of infants born at 35 and 36 weeks gestation: we need to ask more questions. Semin Perinatol. 2006 Feb;30(1):28-33. doi: 10.1053/j.semperi.2006.01.005.
BackgroundHamilton BE, Ventura SJ, Martin JA, and Sutton PD. Preliminary births for 2004. Health E-stats. Hyattsville, MD: National Center for Health Statistics. Released October 28, 2005.
Background: PubMed 16202965Buus-Frank ME. The great imposter. Adv Neonatal Care. 2005 Oct;5(5):233-6. doi: 10.1016/j.adnc.2005.08.012. No abstract available.
Background: PubMed 16396875Hoyert DL, Mathews TJ, Menacker F, Strobino DM, Guyer B. Annual summary of vital statistics: 2004. Pediatrics. 2006 Jan;117(1):168-83. doi: 10.1542/peds.2005-2587.
Background: PubMed 17148006Dudell GG, Jain L. Hypoxic respiratory failure in the late preterm infant. Clin Perinatol. 2006 Dec;33(4):803-30; abstract viii-ix. doi: 10.1016/j.clp.2006.09.006.
Background: PubMed 16549210Laptook A, Jackson GL. Cold stress and hypoglycemia in the late preterm ("near-term") infant: impact on nursery of admission. Semin Perinatol. 2006 Feb;30(1):24-7. doi: 10.1053/j.semperi.2006.01.014.
Background: PubMed 16731281Neu J. Gastrointestinal maturation and feeding. Semin Perinatol. 2006 Apr;30(2):77-80. doi: 10.1053/j.semperi.2006.02.007.
Background: PubMed 16731283Bhutani VK, Johnson L. Kernicterus in late preterm infants cared for as term healthy infants. Semin Perinatol. 2006 Apr;30(2):89-97. doi: 10.1053/j.semperi.2006.04.001.
Background: PubMed 18635431Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008 Jul 17;359(3):262-73. doi: 10.1056/NEJMoa0706475.
Background: PubMed 18165390McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008 Jan;111(1):35-41. doi: 10.1097/01.AOG.0000297311.33046.73.
(The public website of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units (MFMU) Network)Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Data will be shared after completion and publication of the main analyses per NIH policy. Requests can be sent to mfmudatasets@bsc.gwu.edu.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Monica Longo, MD study director

NICHD Project Scientist

Rebecca Clifton, PhD principal investigator

George Washington University

Cynthia Gyamfi Bannerman, MD study chair

Columbia University

17 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Betamethasone in people with Pregnancy and Respiratory Distress Syndrome, run by The George Washington University Biostatistics Center at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Neonatal Composite Outcome (time frame: 72 hours of life). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01222247, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2023.