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

Primary Purpose

Preterm Birth, Premature Birth, Complication of Prematurity

Status
Not yet recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Celestone + placebo
Celestone + Celestone
Sponsored by
McMaster University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Preterm Birth focused on measuring 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

Eligibility Criteria

18 Years - 55 Years (Adult)FemaleDoes not accept healthy volunteers

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. All fetuses must be without compromise as per ultrasound or fetal heart rate monitor (so that waiting 24 hours for the study medication is acceptable).
  3. 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

Sites / Locations

  • John Hunter Hospital
  • The University of Newcastle
  • The Royal Hospital for Women
  • The University of New South Wales, St George Hospital
  • University of Sydney; Westmead Institute for Maternal Fetal Medicine, Westmead Hospital
  • Royal Darwin Hospital
  • Royal Brisbane & Women's Hospital
  • University of Queensland and Ipswich Hospital
  • Mater Centre for Maternal Fetal Medicine
  • The University of Queensland; Mater Research Institute/University of Queensland
  • Townsville Hospital and Health Services
  • University of Adelaide; Women's & Children's Hospital
  • Royal Hobart Hospital
  • Moorabbin Hospital, Monash Health
  • University of Melbourne; Mercy Hospital for Women
  • The Royal Women's Hospital; University of Melbourne
  • The University of Melbourne; Joan Kirner Women's & Children's Sunshine Hospital
  • University of Calgary, Cumming School of Medicine
  • Alberta Health Services; University of Alberta
  • Royal Columbian Hospital
  • Fraser Health, University of British Columbia; Jim Pattison Outpatient Care and Surgery Centre
  • University of British Columbia; BC Women's Hospital
  • Victoria General Hospital
  • University of Manitoba, Health Sciences Centre
  • University of Manitoba; St. Boniface General Hospital
  • Dr. Everett Chalmers Regional Hospital
  • The Moncton Hospital, Horizon Health Network
  • Memorial University, Eastern Health
  • Dalhousie University
  • McMaster University
  • Queen's University, Kingston General Hospital Health Sciences Centre
  • Western University; London Health Sciences Centre, Victoria Hospital
  • University of Ottawa; The Ottawa Hospital
  • Mount Sinai Hospital
  • Sunnybrook Health Sciences Center
  • McGill University, McGill University Health Center, Royal Victoria Hospital
  • Sir Mortimer B. Davis Jewish General Hospital; McGill University
  • The Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal
  • Université Laval, Centre de recherche du CHU de Québec
  • (CIUSSS de l'Estrie-CHUS); Université de Sherbrooke
  • University of Saskatchewan, Regina General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Single-Dose Celestone

Double-Dose Celestone

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Individual components of the above composite primary outcome
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)
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), which has 5 domains: i) Communication, ii) Gross Motor, iii) Fine Motor, iv) Problem Solving, v) Personal-Social and vi) Overall Development (including vision and hearing). Child Behavior Checklist: 4 subscales i) Anxious/Depressed, ii) Aggression, iii) Withdrawn & iv) Hyperactivity subscales. Physician diagnosis of cerebral palsy (parent report).

Full Information

First Posted
October 12, 2021
Last Updated
May 3, 2023
Sponsor
McMaster University
Collaborators
Hamilton Health Sciences Corporation, Canadian Institutes of Health Research (CIHR), Medical Research Future Fund
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1. Study Identification

Unique Protocol Identification Number
NCT05114096
Brief Title
Single Dose of Antenatal Corticosteroids for Pregnancies at Risk of Preterm Delivery (SNACS)
Acronym
SNACS
Official Title
Single Dose of Antenatal Corticosteroids (SNACS) Randomized Controlled Trial for Pregnancies at Risk of Preterm Delivery: To Keep Babies and Children Safe
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 31, 2023 (Anticipated)
Primary Completion Date
June 30, 2026 (Anticipated)
Study Completion Date
June 30, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
McMaster University
Collaborators
Hamilton Health Sciences Corporation, Canadian Institutes of Health Research (CIHR), Medical Research Future Fund

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preterm Birth, Premature Birth, Complication of Prematurity, Obstetric Labor, Premature, Pregnancy Complications
Keywords
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

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Multicentre, blinded, pragmatic, 2 arm non-inferiority RCT
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3254 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single-Dose Celestone
Arm Type
Experimental
Arm Description
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.
Arm Title
Double-Dose Celestone
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Celestone + placebo
Intervention Description
After the first intramuscular injection of Celestone, participants randomized to the "Placebo Comparator" group will receive 1 intramuscular injection of placebo.
Intervention Type
Drug
Intervention Name(s)
Celestone + Celestone
Intervention Description
After the first intramuscular injection of Celestone, participants randomized to the "Active Comparator" group will receive 1 intramuscular injection of Celestone.
Primary Outcome Measure Information:
Title
Perinatal Mortality or Substantial Neonatal Morbidity
Description
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)
Time Frame
approximately 1 month
Secondary Outcome Measure Information:
Title
Individual components of the above composite primary outcome
Description
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)
Time Frame
approximately 1 month
Title
Death or neurosensory/developmental impairment at 24 months
Description
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), which has 5 domains: i) Communication, ii) Gross Motor, iii) Fine Motor, iv) Problem Solving, v) Personal-Social and vi) Overall Development (including vision and hearing). Child Behavior Checklist: 4 subscales i) Anxious/Depressed, ii) Aggression, iii) Withdrawn & iv) Hyperactivity subscales. Physician diagnosis of cerebral palsy (parent report).
Time Frame
approximately 24 months
Other Pre-specified Outcome Measures:
Title
Number of babies who received intubation and duration of invasive mechanical ventilation
Description
Number of babies who received intubation and duration of invasive mechanical ventilation
Time Frame
approximately up to first 6 months of life
Title
Number of babies who received, and duration of, supplemental oxygen (after resuscitation) and other ventilatory support
Description
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
Title
Number of babies with meconium aspiration syndrome
Description
Number of babies with meconium aspiration syndrome.
Time Frame
approximately 1 month
Title
Number of babies with persistent pulmonary hypertension of the newborn
Description
Number of babies with persistent pulmonary hypertension of the newborn.
Time Frame
approximately 1 month
Title
Number of babies with hypoglycemia
Description
Number of babies with hypoglycemia (low plasma glucose < 2.6 mmol/L between 30 minutes and 48 hours of life)
Time Frame
48 hours
Title
Number of babies with neonatal sepsis
Description
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.
Time Frame
7 days
Title
Number of babies with severe retinopathy of prematurity needing treatment
Description
Number of babies with severe retinopathy of prematurity defined as requiring vascular endothelial growth factor (VEGF) or laser or cryotherapy per the local guidelines
Time Frame
approximately first few months of life
Title
Number of babies with patent ductus arteriosus (PDA) needing a closure procedure (surgery or device)
Description
Number of babies with patent ductus arteriosus (PDA) needing a closure procedure (surgery or device)
Time Frame
up to 12 weeks after birth
Title
Anthropometry at birth and at 24 months corrected age
Description
Weight (in grams), length (in centimeters), and head circumference (in centimeters) for birth week as ACS can impact growth
Time Frame
at birth and at 24 months corrected age
Title
Number of babies with severe late brain injury
Description
Periventricular leukomalacia [PVL], i.e. cystic changes in white matter or porencephalic cysts or white matter changes diagnosed by ultrasound or MRI.
Time Frame
up to 20 weeks postnatal
Title
Number of babies with chronic lung disease
Description
Late respiratory morbidity, bronchopulmonary dysplasia (BPD), defined as requiring respiratory support or supplemental oxygen > 36 completed weeks' corrected gestation.
Time Frame
approximately up to first 6 months of life
Title
Apgar score and cord blood pH
Description
Apgar score (at 1 and 5 min) and lowest cord blood pH, regardless of whether arterial or venous.
Time Frame
approximately at birth
Title
Length of stay in an intensive care setting
Description
Length of stay in an intensive care setting such as the neonatal intensive care unit (NICU).
Time Frame
approximately up to first 6 months of life
Title
Use of postnatal corticosteroids
Description
Use of systemic (intravenous or oral) postnatal corticosteroids and type (e.g. hydrocortisone, dexamethasone).
Time Frame
up to 20 weeks postnatal
Title
Number of babies with longterm health care outcomes
Description
Number of babies with reported longterm health care outcomes after initial hospital, such as hospitalizations, and other health care use.
Time Frame
approximately 5 -10 years
Title
Number of babies with longterm education outcomes
Description
Number of babies with reported longterm education or non-health data outcomes, collected through database linkage where possible.
Time Frame
approximately 5 -10 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 All fetuses must be without compromise as per ultrasound or fetal heart rate monitor (so that waiting 24 hours for the study medication is acceptable). 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah D McDonald, MD,MSc,FRCSC
Phone
905-525-9140
Ext
26622
Email
mcdonals@mcmaster.ca
First Name & Middle Initial & Last Name or Official Title & Degree
SNACS Coordinating Centre
Email
SNACS@sunnybrook.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarah D McDonald, MD,MSc,FRCSC
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kellie Murphy, MD,MSc,FRCSC
Organizational Affiliation
University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
John Hunter Hospital
City
Newcastle
State/Province
New South Wales
Country
Australia
Facility Name
The University of Newcastle
City
Newcastle
State/Province
New South Wales
Country
Australia
Facility Name
The Royal Hospital for Women
City
Randwick
State/Province
New South Wales
Country
Australia
Facility Name
The University of New South Wales, St George Hospital
City
Sydney
State/Province
New South Wales
Country
Australia
Facility Name
University of Sydney; Westmead Institute for Maternal Fetal Medicine, Westmead Hospital
City
Westmead
State/Province
New South Wales
Country
Australia
Facility Name
Royal Darwin Hospital
City
Tiwi
State/Province
Northern Territory
Country
Australia
Facility Name
Royal Brisbane & Women's Hospital
City
Herston
State/Province
Queensland
Country
Australia
Facility Name
University of Queensland and Ipswich Hospital
City
Ipswich
State/Province
Queensland
Country
Australia
Facility Name
Mater Centre for Maternal Fetal Medicine
City
South Brisbane
State/Province
Queensland
Country
Australia
Facility Name
The University of Queensland; Mater Research Institute/University of Queensland
City
South Brisbane
State/Province
Queensland
Country
Australia
Facility Name
Townsville Hospital and Health Services
City
Townsville
State/Province
Queensland
Country
Australia
Facility Name
University of Adelaide; Women's & Children's Hospital
City
North Adelaide
State/Province
South Australia
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
Country
Australia
Facility Name
Moorabbin Hospital, Monash Health
City
Clayton
State/Province
Victoria
Country
Australia
Facility Name
University of Melbourne; Mercy Hospital for Women
City
Heidelberg
State/Province
Victoria
Country
Australia
Facility Name
The Royal Women's Hospital; University of Melbourne
City
Parkville
State/Province
Victoria
Country
Australia
Facility Name
The University of Melbourne; Joan Kirner Women's & Children's Sunshine Hospital
City
Saint Albans
State/Province
Victoria
Country
Australia
Facility Name
University of Calgary, Cumming School of Medicine
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Alberta Health Services; University of Alberta
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
Royal Columbian Hospital
City
New Westminster
State/Province
British Columbia
Country
Canada
Facility Name
Fraser Health, University of British Columbia; Jim Pattison Outpatient Care and Surgery Centre
City
Surrey
State/Province
British Columbia
Country
Canada
Facility Name
University of British Columbia; BC Women's Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Victoria General Hospital
City
Victoria
State/Province
British Columbia
Country
Canada
Facility Name
University of Manitoba, Health Sciences Centre
City
Winnipeg
State/Province
Manitoba
Country
Canada
Facility Name
University of Manitoba; St. Boniface General Hospital
City
Winnipeg
State/Province
Manitoba
Country
Canada
Facility Name
Dr. Everett Chalmers Regional Hospital
City
Fredericton
State/Province
New Brunswick
Country
Canada
Facility Name
The Moncton Hospital, Horizon Health Network
City
Moncton
State/Province
New Brunswick
Country
Canada
Facility Name
Memorial University, Eastern Health
City
St. John's
State/Province
Newfoundland and Labrador
Country
Canada
Facility Name
Dalhousie University
City
Halifax
State/Province
Nova Scotia
Country
Canada
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Queen's University, Kingston General Hospital Health Sciences Centre
City
Kingston
State/Province
Ontario
Country
Canada
Facility Name
Western University; London Health Sciences Centre, Victoria Hospital
City
London
State/Province
Ontario
Country
Canada
Facility Name
University of Ottawa; The Ottawa Hospital
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Mount Sinai Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Sunnybrook Health Sciences Center
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
McGill University, McGill University Health Center, Royal Victoria Hospital
City
Montréal
State/Province
Quebec
Country
Canada
Facility Name
Sir Mortimer B. Davis Jewish General Hospital; McGill University
City
Montréal
State/Province
Quebec
Country
Canada
Facility Name
The Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal
City
Montréal
State/Province
Quebec
Country
Canada
Facility Name
Université Laval, Centre de recherche du CHU de Québec
City
Québec City
State/Province
Quebec
Country
Canada
Facility Name
(CIUSSS de l'Estrie-CHUS); Université de Sherbrooke
City
Sherbrooke
State/Province
Quebec
Country
Canada
Facility Name
University of Saskatchewan, Regina General Hospital
City
Saskatoon
State/Province
Saskatchewan
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
An IPD is planned with trial leaders of another half dose Celestone study.
Citations:
PubMed Identifier
32660867
Citation
Ninan K, Morfaw F, Murphy KE, Beyene J, McDonald SD. Neonatal and Maternal Outcomes of Lower Versus Standard Doses of Antenatal Corticosteroids for Women at Risk of Preterm Delivery: A Systematic Review of Randomized Controlled Trials. J Obstet Gynaecol Can. 2021 Jan;43(1):74-81. doi: 10.1016/j.jogc.2020.02.127. Epub 2020 Mar 26.
Results Reference
background
Links:
URL
https://doi.org/10.1016/j.jogc.2020.02.127
Description
Neonatal and Maternal Outcomes of Lower Versus Standard Doses of Antenatal Corticosteroids for Women at Risk of Preterm Delivery: A Systematic Review of Randomized Controlled Trials

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

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