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

NCT ID: NCT04494529

Last Updated: 2023-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2021-08-31

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)

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: PLACEBO_COMPARATOR

12 mg betamethasone + placebo

Intervention Type: DRUG

After the first intramuscular injection of 12 mg of betamethasone, participants randomized to the "Placebo Comparator" group will receive 1 intramuscular injection of placebo.

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).

Group Type: ACTIVE_COMPARATOR

24 mg betamethasone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Sarah McDonald

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sarah D McDonald, MD, MSc, FRCSC

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Kellie Murphy, MD, MSc, FRCSC

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

Locations

McMaster University Medical Centre

Hamilton, Ontario, Canada

Countries

Canada

Other Identifiers

SNACS Pilot Trial

Identifier Type: -

Identifier Source: org_study_id