Antenatal Corticosteroids for Premature Birth

(SNACS Trial)

Recruiting at 41 trial locations

Overseen By SNACS Coordinating Centre

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: McMaster University

Must be taking: Celestone

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe asthma, Lupus, Covid, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

3254 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking systemic corticosteroids for medical conditions during pregnancy, you cannot participate.

What data supports the effectiveness of the drug Celestone, Betamethasone, Celestone Soluspan for premature birth?

Research shows that betamethasone, a component of the drug, has anti-inflammatory effects and is used in other treatments like psoriasis, suggesting it may help reduce inflammation in various conditions. However, there is no direct evidence from the provided studies about its effectiveness specifically for premature birth. ^{1 2 3 4 5}

How does the drug Celestone differ from other treatments for premature birth?

Celestone (betamethasone) is unique for premature birth as it is a corticosteroid that helps mature the baby's lungs before birth, reducing complications. Unlike other treatments, it is specifically used to accelerate lung development in preterm infants, which is crucial for their survival and health. ^{1 4 6 7 8}

What is the purpose of this trial?

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.

Research Team

Sarah D McDonald, MD,MSc,FRCSC

Principal Investigator

McMaster University

Kellie Murphy, MD,MSc,FRCSC

Principal Investigator

University of Toronto

Eligibility Criteria

This trial is for pregnant individuals aged 18-55 at risk of preterm birth between 22 and <35 weeks gestation, who can give informed consent and have received only one dose of Celestone within the last 24 hours. It's not for those on systemic corticosteroids, with severe fetal/patient conditions, or previous trial participation.

Inclusion Criteria

I am pregnant, 18-55, at risk of early delivery, and have had one Celestone dose in the last 24 hours.

Capable of giving informed, written consent.

Exclusion Criteria

I am pregnant with a known severe fetal condition.

Previous participation in this trial (in a previous pregnancy)

I am taking corticosteroids for a condition like lupus, severe asthma, or Covid during my pregnancy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either a placebo or the standard double dose of Celestone to determine non-inferiority for the primary outcome

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neonatal outcomes and long-term health assessments

up to 10 years

Treatment Details

Interventions

• Celestone

Trial Overview The SNACS study is testing if a single dose (12 mg in Canada or 11.4 mg in Australia) of Celestone is as effective as the standard double doses for accelerating fetal lung maturity to reduce risks associated with premature births.

Participant Groups

Group I: Single-Dose Celestone Experimental Treatment 1 Intervention

Having already received the first dose of Celestone as part of eligibility criteria, participants randomized to the experimental "Single-Dose" arm will receive a similar appearing placebo injection.

Group II: Double-Dose Celestone Active Control 1 Intervention

Having already received the first dose of Celestone as part of eligibility criteria, participants randomized to the "Double-Dose" arm will receive the standard 2nd dose of Celestone injected intramuscularly (i.e. they will receive the standard double-dose regimen).

Celestone is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Celestone for:

• Preterm labor
• Respiratory distress syndrome prevention

Approved in United States as Betamethasone for:

• Preterm labor
• Respiratory distress syndrome prevention

Approved in European Union as Betamethasone for:

• Preterm labor
• Respiratory distress syndrome prevention

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Sunnybrook Research Institute

Collaborator

Trials

33

Recruited

216,000+

Women's and Children's Hospital, Australia

Collaborator

Trials

9

Recruited

32,500+

Medical Research Future Fund

Collaborator

Trials

10

Recruited

210,000+

University of Adelaide

Collaborator

Trials

67

Recruited

181,000+

Hamilton Health Sciences Corporation

Collaborator

Trials

380

Recruited

345,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Medical Research Future Fund

Collaborator

Trials

2

Recruited

3,300+

Findings from Research

The combination of calcipotriol and betamethasone dipropionate is effective as a first-line treatment for mild-to-moderate plaque psoriasis, working together to improve skin cell growth and reduce inflammation.

This treatment has a good safety profile based on both short-term (4-12 weeks) and long-term (>1 year) studies, although it should not be used on sensitive areas like the face or in cases of unstable psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcipotriol/betamethasone dipropionate for the treatment of psoriasis. Charakida, A., Dadzie, O., Teixeira, F., et al.[2019]

In a Phase III study involving 426 patients with mild to moderate psoriasis, the aerosol foam formulation of calcipotriene and betamethasone significantly improved treatment success at week 4 compared to the vehicle, with 53.3% of patients achieving success versus only 4.8% in the control group.

The Cal/BD foam not only provided significant reductions in psoriasis severity (mean mPASI score of 2.0 vs. 5.5) but also offered rapid itch relief, demonstrating both efficacy and a favorable safety profile with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Calcipotriene Plus Betamethasone Dipropionate Aerosol Foam in Patients With Psoriasis Vulgaris--a Randomized Phase III Study (PSO-FAST). Leonardi, C., Bagel, J., Yamauchi, P., et al.[2022]

In a study of 10 patients with sub-total villous atrophy treated with topical corticosteroids for 4 months, 5 patients showed symptomatic improvement along with better red cell folate and urinary xylose levels, indicating some efficacy in managing symptoms of coeliac disease.

Despite some improvements in specific markers and enterocyte height, the overall effectiveness of topical corticosteroids was not superior to prednisolone, and significant suppression of the pituitary adrenal axis was observed in most patients, raising concerns about safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical, biochemical and morphological responses of patients with villous atrophy to oral betamethasone valerate and clobetasone butyrate. Bramble, MG., Watson, AJ., Scott, J., et al.[2018]

Amcinonide cream was classified as a very strong corticosteroid, while prednicarbate cream was found to be moderately strong, based on a series of tests including the vasoconstriction test conducted on healthy young individuals.

The vasoconstriction test proved to be an effective screening method for determining the potency of corticosteroid preparations, with results largely consistent across various other tests, although clinical evaluations are recommended for further validation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparative evaluation of the potencies of external corticoids with various test methods]. Koch, EM., Ott, R.[2016]

Calcipotriol and betamethasone aerosol foam (Cal/BD foam) is more effective and preferred by patients compared to traditional gel formulations for treating plaque psoriasis, as shown in a cost-effectiveness analysis.

The analysis indicated that Cal/BD foam is the most cost-effective option, costing $13,609 per quality-adjusted life year (QALY) gained, and even showed a slight cost advantage over the gel formulation when comparing treatment durations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cost-effectiveness analysis of calcipotriol plus betamethasone dipropionate aerosol foam versus gel for the topical treatment of plaque psoriasis. Foley, P., Garrett, S., Ryttig, L.[2019]

In a study involving 24 healthy volunteers, the use of 0.1% betamethasone-17-valerate and 0.05% clobetasol-17-propionate creams significantly reduced skin thickness, indicating a higher atrophogenic potential compared to the vehicle cream.

In contrast, 0.25% prednicarbate cream did not reduce skin thickness, suggesting it has a better safety profile with a favorable balance between anti-inflammatory effects and atrophogenic risks, despite being equipotent to betamethasone for treating atopic eczema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

0.25% prednicarbate cream and the corresponding vehicle induce less skin atrophy than 0.1% betamethasone-17-valerate cream and 0.05% clobetasol-17-propionate cream. Korting, HC., Vieluf, D., Kerscher, M.[2019]

In a study of 64 patients with active distal ulcerative colitis, budesonide enemas were found to be more effective than prednisolone enemas, with 52% of patients healing endoscopically compared to 24% for prednisolone after 4 weeks of treatment.

Budesonide treatment did not cause significant suppression of endogenous cortisol levels, unlike prednisolone, suggesting it may have a better safety profile with fewer adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Danielsson, A., Hellers, G., Lyrenäs, E., et al.[2019]

In a study involving 146 patients with active distal ulcerative colitis, budesonide enemas (2 mg/100 ml) showed similar efficacy to prednisolone enemas (25 mg/100 ml) in improving clinical symptoms and proctoscopy findings after 2 weeks of treatment.

Budesonide enemas did not significantly affect plasma cortisol levels, indicating a potentially safer profile compared to prednisolone, which reduced cortisol by about 30%, suggesting less impact on the hypothalamic-pituitary-adrenal axis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide enema in distal ulcerative colitis. A randomized dose-response trial with prednisolone enema as positive control. The Danish Budesonide Study Group. [2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Calcipotriol/betamethasone dipropionate for the treatment of psoriasis. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Calcipotriene Plus Betamethasone Dipropionate Aerosol Foam in Patients With Psoriasis Vulgaris--a Randomized Phase III Study (PSO-FAST). [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical, biochemical and morphological responses of patients with villous atrophy to oral betamethasone valerate and clobetasone butyrate. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

[Comparative evaluation of the potencies of external corticoids with various test methods]. [2016]

5. England pubmed.ncbi.nlm.nih.gov

A cost-effectiveness analysis of calcipotriol plus betamethasone dipropionate aerosol foam versus gel for the topical treatment of plaque psoriasis. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

0.25% prednicarbate cream and the corresponding vehicle induce less skin atrophy than 0.1% betamethasone-17-valerate cream and 0.05% clobetasol-17-propionate cream. [2019]

7. England pubmed.ncbi.nlm.nih.gov

A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Budesonide enema in distal ulcerative colitis. A randomized dose-response trial with prednisolone enema as positive control. The Danish Budesonide Study Group. [2019]