Single Dose of Antenatal Corticosteroids for Pregnancies at Risk of Preterm Delivery (SNACS)

Study Overview
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Brief Summary
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Antenatal corticosteroids (ACS) reduce the risks of neonatal death and morbidities in preterm infants, such as respiratory distress syndrome. The standard of care for pregnant people at risk of preterm birth includes 2 doses of Celestone (for a total of 24 mg in Canada, or 22.8 mg in Australia) to accelerate fetal lung maturity. The investigators plan to conduct a randomized controlled trial to determine whether half the usual dose (12 mg in Canada, or 11.4 mg in Australia) of Celestone is non-inferior to the standard double doses.

Detailed Description
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Preterm infants are at risk of mortality and morbidity. Antenatal corticosteroids (ACS) reduce the risks of neonatal death and morbidities, such as respiratory distress syndrome. The standard of care for pregnant people at risk of preterm birth includes 2 doses of Celestone to accelerate fetal lung maturity (total 24 mg in Canada, 22.8 mg in Australia). There are no published clinical trial data on the benefits or risks of a single dose of antenatal corticosteroid vs. standard double doses (Ninan et al JOGC 2020). Pregnant people at 22 weeks and 0 days to < 34 weeks and 6 days' gestation at risk of preterm birth with a singleton or twin gestation who have received the first dose of Celestone and consented to the trial will be randomized to receive approximately 24 hours later either an experimental placebo injection (of normal saline) or the standard double dose of Celestone to determine whether the intervention is non-inferior for the primary outcome of a composite of perinatal mortality or substantial morbidity. Please note: Based on Health Canada's' guidance the study phase is 'Other: Off-Label use'. However, on the clincaltrial.gov record, 'Phase 4' is selected as this is the most relevant phase and there is no option to select 'Other'. Please note: McMaster University, Canada is the Canadian Regulatory Sponsor and Overall Sponsor, and the University of Adelaide Australia is the Australian Sponsor.

Official Title
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Single Dose of Antenatal Corticosteroids (SNACS) Randomized Controlled Trial for Pregnancies at Risk of Preterm Delivery: To Keep Babies and Children Safe

Conditions
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Preterm Birth, Premature Birth, Complication of Prematurity, Obstetric Labor, Premature, Pregnancy Complications

Intervention / Treatment
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* Drug: Celestone + placebo
* Drug: Celestone + Celestone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant people, aged 18 to 55 years old, at risk of preterm birth with a singleton or twins between 22 weeks and 0 days and <34 weeks and 6 days gestation who have received only a single dose of Celestone within 24 hours Capable of giving informed, written consent. Exclusion Criteria: Contraindication to corticosteroids Systemic corticosteroids for medical conditions during the pregnancy (e.g. lupus, severe asthma, Covid, etc). Previous participation in this trial (in a previous pregnancy) Known severe/life-threatening fetal or pregnant patient condition (e.g. fetal congenital/chromosomal abnormality) Demise of one or more fetuses after 14 weeks and 0 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicentre, blinded, pragmatic, 2 arm non-inferiority RCT
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-Dose Celestone<br>Having already received the first dose of Celestone as part of eligibility criteria, participants randomized to the experimental Single-Dose arm will receive a similar appearing placebo injection. | Drug: Celestone + placebo<br>* After the first intramuscular injection of Celestone, participants randomized to the Placebo Comparator group will receive 1 intramuscular injection of placebo.<br>|
| Active Comparator: Double-Dose Celestone<br>Having already received the first dose of Celestone as part of eligibility criteria, participants randomized to the Double-Dose arm will receive the standard 2nd dose of Celestone injected intramuscularly (i.e. they will receive the standard double-dose regimen). | Drug: Celestone + Celestone<br>* After the first intramuscular injection of Celestone, participants randomized to the Active Comparator group will receive 1 intramuscular injection of Celestone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perinatal Mortality or Substantial Neonatal Morbidity | Fetal death post-randomization or in hospital neonatal death OR => 1 of respiratory morbidity (requiring surfactant <=48 hrs of life), severe intraventricular hemorrhage (distending/beyond the ventricles, i.e. Grade 3 or 4), or severe bowel problem (necrotizing enterocolitis, Stage 2 or 3) | approximately 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or neurosensory/developmental impairment at 24 months | Death or neurosensory/developmental impairment at 24 months (+/- 6 months; accounting for gestation at birth), mood (anxiety/depression), behavior (aggression), etc as assessed by: Ages and Stages Questionnaire-3 (ASQ) Child Behavior Checklist: 4 subscales Physician diagnosis of cerebral palsy (parent report). | approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premature birth, Preterm birth, Obstetric labour, Betamethasone, Betamethasone Valerate, Betamethasone-17,21-dipropionate, Betamethasone benzoate, Betamethasone sodium phosphate, Anti-Inflammatory Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes and Hormone Antagonists, Physiological Effect of Drugs, Anti-Asthmatic Agents, Respiratory System Agents