Single Dose Antenatal Corticosteroids (SNACS) for Women at Risk of Preterm Birth (SNACS Pilot)

Single Dose Antenatal Corticosteroids (SNACS) Pilot Randomized Control Trial for Women at Risk of Preterm Birth

Antenatal corticosteroids (ACS) reduce the risks of neonatal death and morbidities, such as respiratory distress syndrome, in preterm infants.

Standard of care for women at risk of preterm birth includes 2 doses of 12 mg betamethasone (for a total of 24 mg) to accelerate fetal lung maturity.

We plan to conduct a pilot clinical trial to determine the feasibility of a trial comparing half the usual dose (total 12 mg) of betamethasone to the standard double dose (total 24 mg) of betamethasone.

The results of this pilot will be combined with the full-scale RCT (NCT05114096) for which we have received funding from the Canadian Institutes of Health Research (CIHR).

Study Overview

• Status: Completed
• Conditions: Pregnancy Complications; Obstetric Labor Complications; Preterm Birth; Obstetric Labor, Premature; Complication of Prematurity
• Intervention / Treatment: Drug: 12 mg betamethasone + placebo; Drug: 24 mg betamethasone

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.

Standard of care for women at risk of preterm birth includes 2 doses of 12 mg betamethasone (for a total of 24 mg) to accelerate fetal lung maturity. There are no published clinical trial data on the benefits or risks of a single dose of antenatal corticosteroid vs. standard double doses.

Pilot trials are now viewed as an "almost essential prerequisite" to large, expensive, full scale studies. Thus, we plan to conduct a pilot clinical trial to determine the feasibility of a trial comparing half the usual dose (12 mg of betamethasone + placebo) to the standard double dose (12 mg + 12 mg of betamethasone), as well as the feasibility of the study protocol. Secondary outcomes will include process outcomes and pilot clinical outcomes, that will be combined with the full-scale RCT for which we have received funding from CIHR.

We plan to conduct a 24-month corrected gestational age follow-up, which will consist principally of 2 validated parent-filled questionnaires:

1. Ages and Stages Questionnaire-3 (ASQ)
2. Child Behavior Checklist
3. A single question parent report of whether there has been a physician diagnosis of cerebral palsy. (recommended by our parent partners)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N3Z5
      • McMaster University Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pregnant women at risk of preterm birth with a singleton or twins between =>22+0/7 and <=34+6/7 weeks' gestation
2. Pregnant with either singletons or twins
3. Has already received the first dose of 12 mg intramuscular betamethasone within the past 24 hours
4. All fetuses are alive and without compromise as per ultrasound or fetal heart monitor
5. Is capable of giving informed, written consent in English

Exclusion Criteria:

1. Any contraindications to receiving corticosteroids
2. Requires chronic doses of corticosteroids secondary to a medical condition (e.g. systemic lupus erythematosus, severe asthma, congenital adrenal hyperplasia, etc.)
3. Received any prior doses of antenatal corticosteroids except for the 1st dose of 12 mg intramuscular betamethasone
4. Had any previous participation in this trial
5. Pregnant with a fetus with severe congenital anomaly (e.g. anencephaly, transposition of the great arteries, etc.) or major chromosomal abnormalities (e.g. Trisomy 18, Trisomy 21, etc.)
6. Pregnant with monoamniotic/monochorionic (Mono/Mono) twins

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Single-Dose (12 mg betamethasone + placebo); The standard course of betamethasone consists of 2 intramuscular injections of 12 mg betamethasone 24 hours apart for a total dose of 24 mg. Before enrolment and randomization in the SNACS trial, all women will have received a first 12 mg injection of betamethasone according to local hospital protocols. After this first injection, randomization is performed. Participants randomized to the experimental "Single-Dose" arm will receive a similar appearing placebo injection instead of the standard 2nd dose of 12 mg of betamethasone (i.e. they will receive the experimental single-dose regimen, total 12 mg of betamethasone only from the first injection).	Drug: 12 mg betamethasone + placebo; After the first intramuscular injection of 12 mg of betamethasone, participants randomized to the "Placebo Comparator" group will receive 1 intramuscular injection of placebo.
Active Comparator: Double-Dose (12 mg betamethasone + 12 mg betamethasone); The standard course of betamethasone consists of 2 intramuscular injections of 12 mg betamethasone 24 hours apart for a total dose of 24 mg. Before enrolment and randomization in the SNACS trial, all women will have received a first 12 mg injection of betamethasone according to local hospital protocols. After this first injection, randomization is performed. Participants randomized to the "Double-Dose" arm will receive the standard 2nd dose of 12 mg of betamethasone injected intramuscularly (i.e. they will receive the standard double-dose regimen, total 24 mg of betamethasone).	Drug: 24 mg betamethasone; After the first intramuscular injection of 12 mg of betamethasone, participants randomized to the "Active Comparator" group will receive the standard 2nd intramuscular injection of 12 mg of betamethasone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of conducting a full-scale trial	Feasibility of conducting a full-scale trial will be defined as => 50% recruitment of approached participants	5-6 months
Feasibility of the study protocol	Feasibility of the study intervention will be defined as => 98% compliance with the protocol	5-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Process outcomes	The proportions of patients who: will be approached by the circle of care, and will agree to be approached by the research team, and will agree to participate	5-6 months
Neonatal mortality rates	Pilot clinical data on neonatal mortality, from medical records	5-6 months
Respiratory morbidity rates	Pilot clinical data on respiratory morbidity, from medical records	5-6 months
Severe intraventricular haemorrhage rates	Pilot clinical data on severe intraventricular haemorrhage, from medical records	5-6 months
Rates of severe bowel problems due to necrotizing enterocolitis	Pilot clinical data on severe bowel problems due to necrotizing enterocolitis, from medical records	5-6 months
Duration of mechanical ventilation requiring an endotracheal tube	Pilot clinical data on duration of mechanical ventilation requiring an endotracheal tube, from medical records	5-6 months
Need for supplemental oxygen and duration	Pilot clinical data on need for supplemental oxygen and duration, from medical records	5-6 months
Late respiratory morbidity (i.e. bronchopulmonary dysplasia) rates	Pilot clinical data on late respiratory morbidity (i.e. bronchopulmonary dysplasia), from medical records	5-6 months
Early neonatal sepsis rates	Pilot clinical data on early neonatal sepsis, from medical records	5-6 months
Severe late brain injury (periventricular leukomalacia) rates	Pilot clinical data on severe late brain injury (periventricular leukomalacia), from medical records	5-6 months
Intrauterine fetal demise rates	Pilot clinical data on intrauterine fetal demise, from medical records	5-6 months
Duration of ventilatory support not requiring an endotracheal tube	Pilot clinical data on duration of ventilatory support not requiring an endotracheal tube, from medical records	5-6 months
Rates of hypotension < 48 hours of life requiring treatment with hydrocortisone or inotropic medications	Pilot clinical data on hypotension < 48 hours of life requiring treatment with hydrocortisone or inotropic medications, from medical records	5-6 months
Length of stay in neonatal intensive care unit	Pilot clinical data on length of stay in neonatal intensive care unit, from medical records	5-6 months
Anthropometry composite (<10% of expected weight, length, or head circumference for birth week)	Pilot clinical data on anthropometry (<10% of expected weight, length, or head circumference for birth week), from medical records	5-6 months
Number of infants with retinopathy of prematurity needing treatment	Pilot clinical data on retinopathy of prematurity needing treatment, from medical records	5-6 months
Patent ductus arteriosus needing a closure procedure	Pilot clinical data on number of infants with patent ductus arteriosus needing a closure procedure, from medical records	5-6 months
24-month follow-up	Neurosensory/developmental progress at 24 months corrected gestational age, which will consist principally of 2 validated parent-filled questionnaires: Ages and Stages Questionnaire-3 (ASQ); Child Behavior Checklist; A single-question parent report of whether there has been a physician diagnosis of cerebral palsy.	18-30 months

Collaborators and Investigators

• Sponsor: McMaster University
• Investigators: Principal Investigator: Sarah D McDonald, MD, MSc, FRCSC, McMaster University; Principal Investigator: Kellie Murphy, MD, MSc, FRCSC, University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 28, 2020
• First Posted (Actual): July 31, 2020

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Glucocorticoids; Premature birth; Preterm birth; Hormones; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Respiratory System Agents; Hormone Antagonists; Obstetric labor; Betamethasone Valerate; Betamethasone-17,21-dipropionate; Betamethasone benzoate; Betamethasone sodium phosphate; Hormone Substitutes; Physiological Effect of Drugs
• Additional Relevant MeSH Terms: Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Obstetric Labor Complications; Pregnancy Complications; Obstetric Labor, Premature; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Betamethasone; Betamethasone Valerate; Betamethasone-17,21-dipropionate; Betamethasone benzoate; Betamethasone sodium phosphate
• Other Study ID Numbers: SNACS Pilot Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No