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

Preterm Birth Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05114096
• Other study ID #: 3764
• Status: Recruiting
• Phase: Phase 4
• Start date: July 20, 2023
• Est. completion date: December 31, 2029

Study information

• Verified date: November 2023
• Source: McMaster University
• Contact: Sarah D McDonald, MD,MSc,FRCSC
• Phone: 905-525-9140
• Email: mcdonals[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3254
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Celestone + placebo
After the first intramuscular injection of Celestone, participants randomized to the "Placebo Comparator" group will receive 1 intramuscular injection of placebo.
• Celestone + Celestone
After the first intramuscular injection of Celestone, participants randomized to the "Active Comparator" group will receive 1 intramuscular injection of Celestone.

Locations

Country	Name	City	State
Australia	Moorabbin Hospital, Monash Health	Clayton	Victoria
Australia	University of Melbourne; Mercy Hospital for Women	Heidelberg	Victoria
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	University of Queensland and Ipswich Hospital	Ipswich	Queensland
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	The University of Newcastle	Newcastle	New South Wales
Australia	University of Adelaide; Women's & Children's Hospital	North Adelaide	South Australia
Australia	The Royal Women's Hospital; University of Melbourne	Parkville	Victoria
Australia	The Royal Hospital for Women	Randwick	New South Wales
Australia	The University of Melbourne; Joan Kirner Women's & Children's Sunshine Hospital	Saint Albans	Victoria
Australia	Mater Centre for Maternal Fetal Medicine	South Brisbane	Queensland
Australia	The University of Queensland; Mater Research Institute/University of Queensland	South Brisbane	Queensland
Australia	The University of New South Wales, St George Hospital	Sydney	New South Wales
Australia	Royal Darwin Hospital	Tiwi	Northern Territory
Australia	Townsville Hospital and Health Services	Townsville	Queensland
Australia	University of Sydney; Westmead Institute for Maternal Fetal Medicine, Westmead Hospital	Westmead	New South Wales
Canada	University of Calgary, Cumming School of Medicine	Calgary	Alberta
Canada	Alberta Health Services; University of Alberta	Edmonton	Alberta
Canada	Dr. Everett Chalmers Regional Hospital	Fredericton	New Brunswick
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	McMaster University	Hamilton	Ontario
Canada	Queen's University, Kingston General Hospital Health Sciences Centre	Kingston	Ontario
Canada	Western University; London Health Sciences Centre, Victoria Hospital	London	Ontario
Canada	The Moncton Hospital, Horizon Health Network	Moncton	New Brunswick
Canada	McGill University, McGill University Health Center, Royal Victoria Hospital	Montréal	Quebec
Canada	Sir Mortimer B. Davis Jewish General Hospital; McGill University	Montréal	Quebec
Canada	The Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal	Montréal	Quebec
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	University of Ottawa; The Ottawa Hospital	Ottawa	Ontario
Canada	Université Laval, Centre de recherche du CHU de Québec	Québec City	Quebec
Canada	University of Saskatchewan, Regina General Hospital	Saskatoon	Saskatchewan
Canada	(CIUSSS de l'Estrie-CHUS); Université de Sherbrooke	Sherbrooke	Quebec
Canada	Memorial University, Eastern Health	St. John's	Newfoundland and Labrador
Canada	Fraser Health, University of British Columbia; Jim Pattison Outpatient Care and Surgery Centre	Surrey	British Columbia
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario
Canada	University of British Columbia; BC Women's Hospital	Vancouver	British Columbia
Canada	Victoria General Hospital	Victoria	British Columbia
Canada	University of Manitoba, Health Sciences Centre	Winnipeg	Manitoba
Canada	University of Manitoba; St. Boniface General Hospital	Winnipeg	Manitoba

Sponsors (7)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR), Hamilton Health Sciences Corporation, Medical Research Future Fund, Sunnybrook Research Institute, University of Adelaide, Women's and Children's Hospital, Australia

Countries where clinical trial is conducted

Australia,  Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of babies who received intubation and duration of invasive mechanical ventilation	Number of babies who received intubation and duration of invasive mechanical ventilation	approximately up to first 6 months of life
Other	Number of babies who received, and duration of, supplemental oxygen (after resuscitation) and other ventilatory support	Number of babies who received, and duration of, supplemental oxygen (after resuscitation) and other ventilatory support	approximately up to first 6 months of life
Other	Number of babies with respiratory distress after the initial resuscitation/stabilization and main cause	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
Other	Number of babies with Respiratory distress after the initial resuscitation/stabilization and main cause	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
Other	Number of babies with hypoglycemia	Number of babies with hypoglycemia (low plasma glucose < 2.6 mmol/L between 30 minutes and 48 hours of life)	48 hours
Other	Number of babies with neonatal sepsis	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
Other	Number of babies with severe retinopathy of prematurity needing treatment	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
Other	Number of babies with patent ductus arteriosus (PDA) needing a closure procedure (surgery or device)	Number of babies with patent ductus arteriosus (PDA) needing a closure procedure (surgery or device)	up to 12 weeks after birth
Other	Anthropometry 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
Other	Number of babies with severe late brain injury	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
Other	Number of babies with chronic lung disease	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
Other	Apgar score and cord blood pH	Apgar score (at 1 and 5 min) and lowest cord blood pH, regardless of whether arterial or venous.	approximately at birth
Other	Length of stay in special care or an intensive care setting	Length of stay in an intensive care setting such as the neonatal intensive care unit (NICU).	approximately up to first 6 months of life
Other	Use of postnatal corticosteroids	Use of systemic (intravenous or oral) postnatal corticosteroids and type (e.g. hydrocortisone, dexamethasone).	up to 20 weeks postnatal
Other	Number of babies with longterm health care outcomes	Number of babies with reported longterm health care outcomes after initial hospital, such as hospitalizations, and other health care use.	approximately 5 -10 years
Other	Number of babies with longterm education outcomes	Number of babies with reported longterm education or non-health data outcomes, collected through database linkage where possible.	approximately 5 -10 years
Other	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	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
Primary	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	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

External Links

•   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