Clinical trial NCT05114096: Single Dose of Antenatal Corticosteroids for Pregnancies at Risk of Preterm Delivery (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
Overall status: RECRUITING
Phase: PHASE4
Conditions: 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
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Hamilton Health Sciences Corporation
name: Sunnybrook Research Institute
name: Women's and Children's Hospital, Australia
name: Canadian Institutes of Health Research (CIHR)
name: Medical Research Future Fund
name: University of Adelaide
First posted: 2021-11-09
Enrollment: 3254
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, blinded, pragmatic, 2 arm non-inferiority RCT
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Perinatal Mortality or Substantial Neonatal Morbidity
timeFrame: approximately 1 month
Secondary outcomes:
measure: Death or neurosensory/developmental impairment at 24 months
timeFrame: approximately 24 months
Other outcomes:
measure: Number of babies who received intubation and duration of invasive mechanical ventilation
timeFrame: approximately up to first 6 months of life
measure: Number of babies who received, and duration of, supplemental oxygen (after resuscitation) and other ventilatory support
timeFrame: approximately up to first 6 months of life
measure: Number of babies with respiratory distress after the initial resuscitation/stabilization and main cause
timeFrame: approximately 1 month
measure: Number of babies with Respiratory distress after the initial resuscitation/stabilization and main cause
timeFrame: approximately at birth
measure: Number of babies with hypoglycemia
timeFrame: 48 hours
measure: Number of babies with neonatal sepsis
timeFrame: 7 days
measure: Number of babies with severe retinopathy of prematurity needing treatment
timeFrame: approximately first few months of life
measure: Number of babies with patent ductus arteriosus (PDA) needing a closure procedure (surgery or device)
timeFrame: up to 12 weeks after birth
measure: Anthropometry at birth and at 24 months corrected age
timeFrame: at birth and at 24 months corrected age
measure: Number of babies with severe late brain injury
timeFrame: up to 20 weeks postnatal
measure: Number of babies with chronic lung disease
timeFrame: approximately up to first 6 months of life
measure: Apgar score and cord blood pH
timeFrame: approximately at birth
measure: Length of stay in special care or an intensive care setting
timeFrame: approximately up to first 6 months of life
measure: Use of postnatal corticosteroids
timeFrame: up to 20 weeks postnatal
measure: Number of babies with longterm health care outcomes
timeFrame: approximately 5 -10 years
measure: Number of babies with longterm education outcomes
timeFrame: approximately 5 -10 years
measure: 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
timeFrame: approximately 1 month
Locations:
city: Calgary
country: Canada
facility: University of Calgary, Cumming School of Medicine
state: Alberta
city: Edmonton
country: Canada
facility: Alberta Health Services; University of Alberta
state: Alberta
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Surrey
country: Canada
facility: Fraser Health, University of British Columbia; Jim Pattison Outpatient Care and Surgery Centre
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia; BC Women's Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba, Health Sciences Centre
state: Manitoba
city: Winnipeg
country: Canada
facility: University of Manitoba; St. Boniface General Hospital
state: Manitoba
city: Fredericton
country: Canada
facility: Dr. Everett Chalmers Regional Hospital
state: New Brunswick
city: Moncton
country: Canada
facility: The Moncton Hospital, Horizon Health Network
state: New Brunswick
city: St. John's
country: Canada
facility: Memorial University, Eastern Health
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Dalhousie University; Izaak Walton Killam Health
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Kingston
country: Canada
facility: Queen's University, Kingston General Hospital Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: Western University; London Health Sciences Centre, Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa; The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Montréal
country: Canada
facility: McGill University, McGill University Health Center, Royal Victoria Hospital
state: Quebec
city: Montréal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital; McGill University
state: Quebec
city: Montréal
country: Canada
facility: The Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal
state: Quebec
city: Québec City
country: Canada
facility: Université Laval, Centre de recherche du CHU de Québec
state: Quebec
city: Sherbrooke
country: Canada
facility: (CIUSSS de l'Estrie-CHUS); Université de Sherbrooke
state: Quebec
city: Saskatoon
country: Canada
facility: University of Saskatchewan, Regina General Hospital
state: Saskatchewan
Study officials:
affiliation: McMaster University
name: Sarah D McDonald, MD,MSc,FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto
name: Kellie Murphy, MD,MSc,FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
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.