Budesonide + Surfactant for Premature Birth Complications

(BiB Trial)

Recruiting at 18 trial locations

Overseen By Abhik Das, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: NICHD Neonatal Research Network

Must be taking: Surfactant

Must not be taking: Systemic steroids, Indomethacin

Disqualifiers: Terminal illness, Major malformations, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

1160 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but it does exclude infants who have received certain medications like systemic steroids or indomethacin before enrollment.

What data supports the effectiveness of the drug Budesonide for premature birth complications?

Research shows that Budesonide, when used in very low birthweight infants at high risk for chronic lung disease, helped more infants be extubated and reduced the need for additional treatments. This suggests it may help improve lung function in premature infants. ^{1 2 3 4 5}

Is Budesonide safe for use in humans?

Budesonide has been used safely in children and adults for conditions like asthma, but some people have reported side effects like headaches, trouble breathing, and blurred vision when used in nasal irrigation. ^{1 2 3 6 7}

How is the drug Budesonide + Surfactant unique for treating premature birth complications?

The combination of Budesonide and Surfactant is unique because it is used early through the airway to prevent bronchopulmonary dysplasia (a lung condition) in premature infants with respiratory distress syndrome, offering a novel approach compared to standard treatments. ^{1 2 5 8 9}

What is the purpose of this trial?

This trial tests a mix of a steroid and a lung-helping substance on very premature babies to reduce severe lung problems or death. The treatment works by reducing lung inflammation and helping the lungs stay open. Steroids like dexamethasone have been used to treat and prevent chronic lung disease in infants, showing beneficial effects.

Research Team

Namasivayam Ambalavanan, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

The BiB Trial is for liveborn infants born between 22 and 28 weeks of gestation or weighing between 401 - 1000 grams. They must be less than 48 hours old and require surfactant treatment. Infants with certain conditions, previous steroid use, enrollment in another trial, or major malformations are not eligible.

Inclusion Criteria

I am approved to receive surfactant therapy.

My baby is 48 hours old or younger.

My baby was born between 22 and 28 weeks of pregnancy or weighed between 401 and 1000 grams at birth.

Exclusion Criteria

My baby or I have used, or plan to use, indomethacin for IVH prevention or PDA treatment.

Enrollment in a conflicting clinical trial

You have certain infections that you were born with, such as confirmed sepsis or congenital CMV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 days

Randomization and Initial Treatment

Infants are randomized to receive either budesonide with surfactant or surfactant alone within 48 hours of birth

2 days

1 visit (in-person)

Treatment Monitoring

Participants are monitored for the development of BPD or death until 36 weeks' post-menstrual age

Up to 36 weeks' post-menstrual age

Follow-up

Participants are monitored for severe neurodevelopmental impairment or death at 2-year follow-up

22-26 months corrected age

Treatment Details

Interventions

• Budesonide
• Surfactant

Trial Overview This study tests if giving budesonide combined with surfactant directly into the windpipe reduces death or bronchopulmonary dysplasia (a lung condition) in extremely premature babies by the time they reach a corrected age of about nine months.

Participant Groups

Group I: budesonide with surfactant Experimental Treatment 1 Intervention

Infants randomized to the intervention arm receive a dose of surfactant (poractant alfa; Curosurf) mixed with budesonide (Pulmicort nebulizing suspension) within 50 hours of birth and administered via endotracheal tube.

Group II: surfactant alone Active Control 1 Intervention

Infants randomized to the active control arm receive a dose of surfactant (poractant alfa; Curosurf).

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

Approved in European Union as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Crohn's disease
• Ulcerative colitis
• Microscopic colitis
• Eosinophilic esophagitis
• Primary immunoglobulin A nephropathy

Approved in United States as Entocort EC for:

• Crohn's disease
• Ulcerative colitis
• Primary immunoglobulin A nephropathy
• Eosinophilic esophagitis

Approved in Canada as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis

Who Is Running the Clinical Trial?

NICHD Neonatal Research Network

Lead Sponsor

Trials

62

Recruited

209,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Findings from Research

Budesonide, an inhalation glucocorticosteroid, significantly improved asthma symptoms in 20 patients, showing a response by the end of the first week of treatment, with a notable reduction in acute asthma episodes and decreased reliance on short-acting beta 2-agonists.

After 12 months of treatment, budesonide improved lung function, as indicated by a 31% reduction in peak expiratory velocity variability, but did not fully normalize the bronchial mucosa, suggesting that longer treatment may be necessary for complete recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinicomorphological assessment of budesonide efficiency in patients with bronchial asthma]. Budkova, AA., Volkova, LI., Budkov, SR., et al.[2006]

Budesonide inhalation suspension significantly improves both nighttime and daytime asthma symptoms in children under 4 years and those 4 years and older, based on a retrospective analysis of two randomized studies involving children aged 6 months to 8 years.

The treatment is generally safe, with no significant differences in adverse events between age groups, although a notable effect on hypothalamic-pituitary-adrenal-axis function was observed in younger children at the lowest dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily budesonide inhalation suspension in infants and children or = 4 years of age with persistent asthma. Scott, MB., Ellis, MH., Cruz-Rivera, M., et al.[2019]

In a study involving 159 adults with moderate-to-severe asthma, budesonide delivered via an inhaler significantly reduced the need for oral glucocorticosteroids (GCSs) by 79-83% compared to only 27% in the placebo group, indicating its efficacy in managing asthma while minimizing systemic steroid use.

Approximately two-thirds of participants using budesonide were able to completely stop oral corticosteroids, and they also experienced improvements in lung function and asthma symptoms, suggesting that budesonide not only spares oral GCSs but also maintains or enhances asthma control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group. Nelson, HS., Bernstein, IL., Fink, J., et al.[2019]

From 2007 to 2022, the FDA received 119 reports regarding the off-label use of budesonide nasal irrigation, primarily from patients.

Adverse events associated with this usage included headaches, difficulty breathing (dyspnea), and blurred vision, highlighting potential safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022. Rathi, VK., Sawicki, NW., Schlosser, RJ., et al.[2023]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinicomorphological assessment of budesonide efficiency in patients with bronchial asthma]. [2006]

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

Once-daily budesonide inhalation suspension in infants and children or = 4 years of age with persistent asthma. [2019]

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

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group. [2019]

4. Norway pubmed.ncbi.nlm.nih.gov

Budesonide delivered by dosimetric jet nebulization to preterm very low birthweight infants at high risk for development of chronic lung disease. [2022]

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

Budesonide inhalation suspension: a nebulized corticosteroid for persistent asthma. [2019]

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

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022. [2023]

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

Safety profile of budesonide inhalation suspension in the pediatric population: worldwide experience. [2006]

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

Effectiveness and safety of early combined utilization of budesonide and surfactant by airway for bronchopulmonary dysplasia prevention in premature infants with RDS: A meta-analysis. [2022]

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

Effect of commercial nasal steroid preparation on bacterial growth. [2020]