Clinical trial NCT04494529: Single Dose Antenatal Corticosteroids (SNACS) for Women at Risk of Preterm Birth
Official title: Single Dose Antenatal Corticosteroids (SNACS) Pilot Randomized Control Trial for Women at Risk of Preterm Birth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preterm Birth
Complication of Prematurity
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Keywords: Premature birth
Preterm birth
Obstetric labor
Betamethasone Valerate
Betamethasone-17,21-dipropionate
Betamethasone benzoate; Betamethasone sodium phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormone Substitutes
Hormone Antagonists
Physiological Effect of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2020-07-31
Enrollment: 30
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pilot double-blind randomized controlled trial
Primary purpose: OTHER

Brief summary: 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).

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)

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of conducting a full-scale trial
timeFrame: 5-6 months
measure: Feasibility of the study protocol
timeFrame: 5-6 months
Secondary outcomes:
measure: Process outcomes
timeFrame: 5-6 months
measure: Neonatal mortality rates
timeFrame: 5-6 months
measure: Respiratory morbidity rates
timeFrame: 5-6 months
measure: Severe intraventricular haemorrhage rates
timeFrame: 5-6 months
measure: Rates of severe bowel problems due to necrotizing enterocolitis
timeFrame: 5-6 months
measure: Duration of mechanical ventilation requiring an endotracheal tube
timeFrame: 5-6 months
measure: Need for supplemental oxygen and duration
timeFrame: 5-6 months
measure: Late respiratory morbidity (i.e. bronchopulmonary dysplasia) rates
timeFrame: 5-6 months
measure: Early neonatal sepsis rates
timeFrame: 5-6 months
measure: Severe late brain injury (periventricular leukomalacia) rates
timeFrame: 5-6 months
measure: Intrauterine fetal demise rates
timeFrame: 5-6 months
measure: Duration of ventilatory support not requiring an endotracheal tube
timeFrame: 5-6 months
measure: Rates of hypotension < 48 hours of life requiring treatment with hydrocortisone or inotropic medications
timeFrame: 5-6 months
measure: Length of stay in neonatal intensive care unit
timeFrame: 5-6 months
measure: Anthropometry composite (<10% of expected weight, length, or head circumference for birth week)
timeFrame: 5-6 months
measure: Number of infants with retinopathy of prematurity needing treatment
timeFrame: 5-6 months
measure: Patent ductus arteriosus needing a closure procedure
timeFrame: 5-6 months
measure: 24-month follow-up
timeFrame: 18-30 months
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
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: