Budesonide + Surfactant for Premature Birth Complications

(BiB Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining budesonide (a corticosteroid) with surfactant can improve breathing and reduce the risk of serious lung problems or death in extremely preterm infants. The goal is to determine if this combination is more effective than surfactant alone. Babies born very early, between 22 to 28 weeks of pregnancy, who require surfactant and are less than 48 hours old, may qualify for this trial. Participants will receive either the combination treatment or surfactant alone. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for preterm infants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using budesonide with surfactant is generally safe for very premature babies. Studies have found that this treatment does not significantly increase the risk of serious side effects compared to using surfactant alone. In some studies, the combination has even been linked to better outcomes, such as fewer breathing problems like bronchopulmonary dysplasia (BPD), a long-term lung condition in premature infants.

One study found that adding budesonide to surfactant did not greatly affect survival rates without BPD, but it also did not cause new safety issues. This suggests the treatment is relatively safe for these vulnerable babies. Overall, evidence supports the safety of using budesonide with surfactant to help reduce lung problems in premature infants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining budesonide with surfactant for treating complications in premature births because it introduces a new way to deliver anti-inflammatory effects directly to the lungs of newborns. Unlike traditional surfactant therapy, which primarily helps with breathing by reducing surface tension in the lungs, the addition of budesonide—a corticosteroid—targets inflammation at the source. This approach could potentially improve outcomes by addressing both lung immaturity and inflammation simultaneously, offering a more comprehensive treatment option for these vulnerable infants.

What evidence suggests that this trial's treatments could be effective for reducing bronchopulmonary dysplasia in preterm infants?

This trial will compare the use of budesonide with surfactant to surfactant alone in very premature babies. Research has shown that combining budesonide with surfactant can reduce lung problems like bronchopulmonary dysplasia (BPD). One study found that this combination improved breathing more than surfactant alone. Another study showed that babies receiving both treatments had fewer cases of BPD. Administered directly into the lungs, this treatment helps them function better. Overall, strong evidence supports this approach in reducing lung issues in extremely premature infants. ^{1 2 6 7 8}

Who Is on the Research Team?

Namasivayam Ambalavanan, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11717239/

Efficacy of pulmonary surfactant with budesonide in premature ... Our study showed that the administration of PS with budesonide significantly improved respiratory outcomes, including the incidence of BPD, duration of ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ppul.71308?af=R

Airway Administration of Budesonide Combined With ... Objective To evaluate the effectiveness and safety of using budesonide in combination with pulmonary surfactant compared with the pulmonary ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12058727/

Meta-analysis of budesonide and surfactant combination ... This meta-analysis evaluates the effectiveness of combining budesonide and surfactant in preventing BPD in preterm neonates compared to surfactant alone.

4. journals.lww.com journals.lww.com/jocn/fulltext/2023/12040/budesonide_and_surfactant_combination_for.1.aspx

Budesonide and Surfactant Combination for Treatment of... In this study, we investigate the effectiveness of intratracheal injection of Surfactant + budesonide in premature infants with RDS.

5. bmcpediatr.biomedcentral.com bmcpediatr.biomedcentral.com/articles/10.1186/s12887-024-04736-9

a single-blind randomized clinical trial | BMC Pediatrics The findings of our study show that infants under 30 weeks with respiratory distress benefit from the combination of surfactant and budesonide ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04545866

NCT04545866 | The Budesonide in Babies (BiB) Trial Recent randomized trials have indicated a lower incidence of BPD/death with the use of a combination of budesonide with surfactant (budesonide + surfactant) ...

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2826118

Intratracheal Budesonide Mixed With Surfactant for ... In extremely preterm infants receiving surfactant, early intratracheal budesonide may have little to no effect on survival free of bronchopulmonary dysplasia.

8. mdpi.com mdpi.com/1648-9144/61/8/1329

Comparative Efficacy and Safety Profile of the Combination ... Conclusions: The combination of pulmonary surfactant and budesonide decreases the occurrence of BPD, duration of mechanical ventilation, length of hospital stay ...