Complication of Prematurity, Obstetric Labor Complications, Obstetric Labor, Premature, Pregnancy Complications, Preterm Birth
Conditions
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
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)
Interventions
DRUG12 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.
DRUG24 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.
Sponsors
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Pilot double-blind randomized controlled trial
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of conducting a full-scale trial | 5-6 months | Feasibility of conducting a full-scale trial will be defined as =\> 50% recruitment of approached participants |
| Feasibility of the study protocol | 5-6 months | Feasibility of the study intervention will be defined as =\> 98% compliance with the protocol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of severe bowel problems due to necrotizing enterocolitis | 5-6 months | Pilot clinical data on severe bowel problems due to necrotizing enterocolitis, from medical records |
| Process outcomes | 5-6 months | 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 |
| Neonatal mortality rates | 5-6 months | Pilot clinical data on neonatal mortality, from medical records |
| Duration of mechanical ventilation requiring an endotracheal tube | 5-6 months | Pilot clinical data on duration of mechanical ventilation requiring an endotracheal tube, from medical records |
| Need for supplemental oxygen and duration | 5-6 months | Pilot clinical data on need for supplemental oxygen and duration, from medical records |
| Late respiratory morbidity (i.e. bronchopulmonary dysplasia) rates | 5-6 months | Pilot clinical data on late respiratory morbidity (i.e. bronchopulmonary dysplasia), from medical records |
| Early neonatal sepsis rates | 5-6 months | Pilot clinical data on early neonatal sepsis, from medical records |
| Severe late brain injury (periventricular leukomalacia) rates | 5-6 months | Pilot clinical data on severe late brain injury (periventricular leukomalacia), from medical records |
| Respiratory morbidity rates | 5-6 months | Pilot clinical data on respiratory morbidity, from medical records |
| Duration of ventilatory support not requiring an endotracheal tube | 5-6 months | Pilot clinical data on duration of ventilatory support not requiring an endotracheal tube, from medical records |
| Rates of hypotension < 48 hours of life requiring treatment with hydrocortisone or inotropic medications | 5-6 months | Pilot clinical data on hypotension \< 48 hours of life requiring treatment with hydrocortisone or inotropic medications, from medical records |
| Length of stay in neonatal intensive care unit | 5-6 months | Pilot clinical data on length of stay in neonatal intensive care unit, from medical records |
| Anthropometry composite (<10% of expected weight, length, or head circumference for birth week) | 5-6 months | Pilot clinical data on anthropometry (\<10% of expected weight, length, or head circumference for birth week), from medical records |
| Number of infants with retinopathy of prematurity needing treatment | 5-6 months | Pilot clinical data on retinopathy of prematurity needing treatment, from medical records |
| Patent ductus arteriosus needing a closure procedure | 5-6 months | Pilot clinical data on number of infants with patent ductus arteriosus needing a closure procedure, from medical records |
| 24-month follow-up | 18-30 months | Neurosensory/developmental progress at 24 months corrected gestational age, 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. |
| Intrauterine fetal demise rates | 5-6 months | Pilot clinical data on intrauterine fetal demise, from medical records |
| Severe intraventricular haemorrhage rates | 5-6 months | Pilot clinical data on severe intraventricular haemorrhage, from medical records |
Countries
Canada
Outcome results
None listed