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

November 16, 2023 updated by: McMaster University

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

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.

Study Overview

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

3254

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • New South Wales
      • Newcastle, New South Wales, Australia
        • Not yet recruiting
        • John Hunter Hospital
      • Newcastle, New South Wales, Australia
        • Not yet recruiting
        • The University of Newcastle
      • Randwick, New South Wales, Australia
        • Not yet recruiting
        • The Royal Hospital for Women
      • Sydney, New South Wales, Australia
        • Not yet recruiting
        • The University of New South Wales, St George Hospital
      • Westmead, New South Wales, Australia
        • Not yet recruiting
        • University of Sydney; Westmead Institute for Maternal Fetal Medicine, Westmead Hospital
    • Northern Territory
      • Tiwi, Northern Territory, Australia
        • Not yet recruiting
        • Royal Darwin Hospital
    • Queensland
      • Herston, Queensland, Australia
        • Not yet recruiting
        • Royal Brisbane & Women's Hospital
      • Ipswich, Queensland, Australia
        • Not yet recruiting
        • University of Queensland and Ipswich Hospital
      • South Brisbane, Queensland, Australia
        • Not yet recruiting
        • Mater Centre for Maternal Fetal Medicine
      • South Brisbane, Queensland, Australia
        • Not yet recruiting
        • The University of Queensland; Mater Research Institute/University of Queensland
      • Townsville, Queensland, Australia
        • Not yet recruiting
        • Townsville Hospital and Health Services
    • South Australia
      • North Adelaide, South Australia, Australia
        • Not yet recruiting
        • University of Adelaide; Women's & Children's Hospital
    • Tasmania
      • Hobart, Tasmania, Australia
        • Not yet recruiting
        • Royal Hobart Hospital
    • Victoria
      • Clayton, Victoria, Australia
        • Not yet recruiting
        • Moorabbin Hospital, Monash Health
      • Heidelberg, Victoria, Australia
        • Not yet recruiting
        • University of Melbourne; Mercy Hospital for Women
      • Parkville, Victoria, Australia
        • Not yet recruiting
        • The Royal Women's Hospital; University of Melbourne
      • Saint Albans, Victoria, Australia
        • Not yet recruiting
        • The University of Melbourne; Joan Kirner Women's & Children's Sunshine Hospital
    • Alberta
      • Calgary, Alberta, Canada
        • Not yet recruiting
        • University of Calgary, Cumming School of Medicine
      • Edmonton, Alberta, Canada
        • Not yet recruiting
        • Alberta Health Services; University of Alberta
    • British Columbia
      • New Westminster, British Columbia, Canada
        • Not yet recruiting
        • Royal Columbian Hospital
      • Surrey, British Columbia, Canada
        • Not yet recruiting
        • Fraser Health, University of British Columbia; Jim Pattison Outpatient Care and Surgery Centre
      • Vancouver, British Columbia, Canada
        • Not yet recruiting
        • University of British Columbia; BC Women's Hospital
      • Victoria, British Columbia, Canada
        • Not yet recruiting
        • Victoria General Hospital
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • Not yet recruiting
        • University of Manitoba, Health Sciences Centre
      • Winnipeg, Manitoba, Canada
        • Not yet recruiting
        • University of Manitoba; St. Boniface General Hospital
    • New Brunswick
      • Fredericton, New Brunswick, Canada
        • Not yet recruiting
        • Dr. Everett Chalmers Regional Hospital
      • Moncton, New Brunswick, Canada
        • Not yet recruiting
        • The Moncton Hospital, Horizon Health Network
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada
        • Not yet recruiting
        • Memorial University, Eastern Health
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Not yet recruiting
        • Dalhousie University
    • Ontario
      • Hamilton, Ontario, Canada
        • Recruiting
        • McMaster University
      • Kingston, Ontario, Canada
        • Not yet recruiting
        • Queen's University, Kingston General Hospital Health Sciences Centre
      • London, Ontario, Canada
        • Not yet recruiting
        • Western University; London Health Sciences Centre, Victoria Hospital
      • Ottawa, Ontario, Canada
        • Not yet recruiting
        • University of Ottawa; The Ottawa Hospital
      • Toronto, Ontario, Canada
        • Not yet recruiting
        • Mount Sinai Hospital
      • Toronto, Ontario, Canada
        • Not yet recruiting
        • Sunnybrook Health Sciences Center
    • Quebec
      • Montréal, Quebec, Canada
        • Not yet recruiting
        • McGill University, McGill University Health Center, Royal Victoria Hospital
      • Montréal, Quebec, Canada
        • Not yet recruiting
        • Sir Mortimer B. Davis Jewish General Hospital; McGill University
      • Montréal, Quebec, Canada
        • Not yet recruiting
        • The Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal
      • Québec City, Quebec, Canada
        • Not yet recruiting
        • Université Laval, Centre de recherche du CHU de Québec
      • Sherbrooke, Quebec, Canada
        • Not yet recruiting
        • (CIUSSS de l'Estrie-CHUS); Université de Sherbrooke
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada
        • Not yet recruiting
        • University of Saskatchewan, Regina General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 53 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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
  2. Capable of giving informed, written consent.

Exclusion Criteria:

  1. Contraindication to corticosteroids
  2. Systemic corticosteroids for medical conditions during the pregnancy (e.g. lupus, severe asthma, Covid, etc).
  3. Previous participation in this trial (in a previous pregnancy)
  4. Known severe/life-threatening fetal or pregnant patient condition (e.g. fetal congenital/chromosomal abnormality)
  5. Demise of one or more fetuses after 14 weeks and 0 days

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single-Dose Celestone
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.
After the first intramuscular injection of Celestone, participants randomized to the "Placebo Comparator" group will receive 1 intramuscular injection of placebo.
Active Comparator: Double-Dose Celestone
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).
After the first intramuscular injection of Celestone, participants randomized to the "Active Comparator" group will receive 1 intramuscular injection of Celestone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Perinatal Mortality or Substantial Neonatal Morbidity
Time Frame: approximately 1 month
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
Time Frame: approximately 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:

  1. Ages and Stages Questionnaire-3 (ASQ)
  2. Child Behavior Checklist: 4 subscales
  3. Physician diagnosis of cerebral palsy (parent report).
approximately 24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of babies who received intubation and duration of invasive mechanical ventilation
Time Frame: approximately up to first 6 months of life
Number of babies who received intubation and duration of invasive mechanical ventilation
approximately up to first 6 months of life
Number of babies who received, and duration of, supplemental oxygen (after resuscitation) and other ventilatory support
Time Frame: approximately up to first 6 months of life
Number of babies who received, and duration of, supplemental oxygen (after resuscitation) and other ventilatory support
approximately up to first 6 months of life
Number of babies with hypoglycemia
Time Frame: 48 hours
Number of babies with hypoglycemia (low plasma glucose < 2.6 mmol/L between 30 minutes and 48 hours of life)
48 hours
Number of babies with neonatal sepsis
Time Frame: 7 days
Number of babies with neonatal sepsis within 7 days of birth, defined as a positive (bacterial, viral or fungal): blood culture or cerebrospinal fluid culture (or gram stain) or urine culture by sterile collection.
7 days
Number of babies with severe retinopathy of prematurity needing treatment
Time Frame: approximately first few months of life
Number of babies with severe retinopathy of prematurity defined as requiring vascular endothelial growth factor (VEGF) or laser or cryotherapy per the local guidelines
approximately first few months of life
Number of babies with patent ductus arteriosus (PDA) needing a closure procedure (surgery or device)
Time Frame: up to 12 weeks after birth
Number of babies with patent ductus arteriosus (PDA) needing a closure procedure (surgery or device)
up to 12 weeks after birth
Anthropometry at birth and at 24 months corrected age
Time Frame: at birth and at 24 months corrected age
Weight (in grams), length (in centimeters), and head circumference (in centimeters) for birth week as ACS can impact growth
at birth and at 24 months corrected age
Number of babies with severe late brain injury
Time Frame: up to 20 weeks postnatal
Periventricular leukomalacia [PVL], i.e. cystic changes in white matter or porencephalic cysts or white matter changes diagnosed by ultrasound or MRI.
up to 20 weeks postnatal
Number of babies with chronic lung disease
Time Frame: approximately up to first 6 months of life
Late respiratory morbidity, bronchopulmonary dysplasia (BPD), defined as requiring respiratory support or supplemental oxygen > 36 completed weeks' corrected gestation.
approximately up to first 6 months of life
Apgar score and cord blood pH
Time Frame: approximately at birth
Apgar score (at 1 and 5 min) and lowest cord blood pH, regardless of whether arterial or venous.
approximately at birth
Use of postnatal corticosteroids
Time Frame: up to 20 weeks postnatal
Use of systemic (intravenous or oral) postnatal corticosteroids and type (e.g. hydrocortisone, dexamethasone).
up to 20 weeks postnatal
Number of babies with longterm health care outcomes
Time Frame: approximately 5 -10 years
Number of babies with reported longterm health care outcomes after initial hospital, such as hospitalizations, and other health care use.
approximately 5 -10 years
Number of babies with longterm education outcomes
Time Frame: approximately 5 -10 years
Number of babies with reported longterm education or non-health data outcomes, collected through database linkage where possible.
approximately 5 -10 years
Number of babies with respiratory distress after the initial resuscitation/stabilization and main cause
Time Frame: approximately 1 month
Number of babies with respiratory distress after the initial resuscitation/stabilization and main cause (such as respiratory distress syndrome, pneumothorax/pneumomediastinum, pneumonia, transient tachypnea of the newborn, meconium aspiration syndrome, persistent pulmonary hypertension of the newborn)
approximately 1 month
Number of babies with Respiratory distress after the initial resuscitation/stabilization and main cause
Time Frame: approximately at birth
Respiratory distress after the initial resuscitation/stabilization and main cause (such as respiratory distress syndrome, pneumothorax/pneumomediastinum, pneumonia, transient tachypnea of the newborn, meconium aspiration syndrome, persistent pulmonary hypertension of the newborn),
approximately at birth
Length of stay in special care or an intensive care setting
Time Frame: approximately up to first 6 months of life
Length of stay in an intensive care setting such as the neonatal intensive care unit (NICU).
approximately up to first 6 months of life
Number of participants with fetal death post-randomization or in hospital neonatal death OR => 1 of respiratory morbidity, severe intraventricular hemorrhage , or severe bowel problem
Time Frame: approximately 1 month
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Sarah D McDonald, MD,MSc,FRCSC, McMaster University
  • Principal Investigator: Kellie Murphy, MD,MSc,FRCSC, University of Toronto
  • Principal Investigator: Jodie Dodd, MD, The University of Adelaide, Australia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 20, 2023

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

October 12, 2021

First Submitted That Met QC Criteria

October 28, 2021

First Posted (Actual)

November 9, 2021

Study Record Updates

Last Update Posted (Actual)

November 18, 2023

Last Update Submitted That Met QC Criteria

November 16, 2023

Last Verified

November 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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