This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for The Budesonide in Babies (BiB) Trial (NCT04545866), a randomized phase 3 study. The primary outcome is Physiologic BPD or Death by 36 Weeks PMA.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04545866 |
| Phase | Phase 3 |
| Condition | Bronchopulmonary Dysplasia (BPD), Respiratory Distress Syndrome, Prematurity; Extreme |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 642 |
| Arms in the primary outcome | n/a |
| Lead sponsor | NICHD Neonatal Research Network |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns extremely preterm infants with neonatal respiratory conditions, including respiratory distress syndrome and risk of bronchopulmonary dysplasia (BPD). The primary outcome population is described as an intent-to-treat group comprising randomized infants who provided outcome data. The registry record does not give further eligibility details in the information available for this analysis.
Intervention
Infants in the intervention arm receive surfactant (poractant alfa; Curosurf) mixed with budesonide (Pulmicort nebulizing suspension). The mixture is administered through an endotracheal tube within 50 hours of birth.
Comparator
The active control is a dose of surfactant (poractant alfa; Curosurf) alone. Both arms therefore include surfactant; the assigned treatment contrast is the addition of budesonide to surfactant.
Primary question
The trial asks whether assignment to budesonide with surfactant, compared with surfactant alone, changes the occurrence of physiologic BPD or death by 36 weeks’ post-menstrual age (PMA). This is a composite outcome: an infant is counted as having the outcome if physiologic BPD is diagnosed or death occurs by that time. The registry record defines how BPD status is assessed, but does not report an arm-by-arm primary outcome estimate or its uncertainty.
3. Trial Design
The Budesonide in Babies Trial is registered as a Phase 3, randomized, masked, active-controlled, multicenter trial with a parallel-group model. The registry lists enrollment as 642 and status as active, not recruiting. It lists a study start date of 2021-04-01 and a primary completion date of 2024-09-05; these dates do not, by themselves, establish that outcome results have been posted.
Random assignment places infants in either the budesonide-with-surfactant arm or the surfactant-alone arm. The registry describes quadruple masking, but the information available does not identify the masked roles or explain how masking was maintained. The active control gives both groups surfactant, making the assigned contrast the addition of budesonide to that treatment.
The intervention arm receives a surfactant dose mixed with budesonide within 50 hours of birth, administered via endotracheal tube. The control arm receives a dose of surfactant. The primary outcome is assessed from randomization to 36 weeks PMA. Secondary outcomes listed in the registry include death by 36 weeks PMA, physiologic BPD, grade of BPD severity, severe BPD, and use of additional postnatal steroids.
The registry record does not report the rationale for the enrollment target, detailed eligibility criteria, allocation-concealment procedures, or the full analysis plan. Those details should not be inferred from the randomized and masked design labels alone.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: One infant was randomized and treated in error after the parent/guardian declined consent. The infant was withdrawn from the trial upon discovery of the protocol violation. At the parent's request, the infant's data have been fully redacted. No data are available for reporting or analysis (including treatment allocation), and this participant is excluded from the intention to treat (ITT) population.
Overall Study
| Stage | Budesonide + Surfactant | Surfactant Alone |
|---|---|---|
| STARTED | 323 | 318 |
| COMPLETED | 321 | 318 |
| NOT COMPLETED | 2 | 0 |
Reasons for not completing this period:
| Reason | Budesonide + Surfactant | Surfactant Alone |
|---|---|---|
| Withdrawal by Parent(s)/Legal Guardian(s) | 1 | 0 |
| Withdrawal by Physician | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: An intent-to-treat (ITT) analysis which included all infants participants who were randomized and who provided outcome data.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | BUDE | SURF | Total |
|---|---|---|---|---|
| Participants analysed | 323 | 318 | 641 | |
| Age, Continuous | weeks | 25.8 (SD 1.9) | 25.9 (SD 2) | 25.9 (SD 1.9) |
| Age, Customized: Greater Than or Equal to 26 0/7 weeks | Participants | 185 | 188 | 373 |
| Age, Customized: Less Than 26 0/7 weeks | Participants | 138 | 130 | 268 |
| Sex/Gender, Customized: Female | Participants | 163 | 156 | 319 |
| Sex/Gender, Customized: Male | Participants | 158 | 162 | 320 |
| Sex/Gender, Customized: Missing | Participants | 2 | 0 | 2 |
| Race/Ethnicity, Customized: Black or African America | Participants | 101 | 122 | 223 |
| Race/Ethnicity, Customized: Other | Participants | 21 | 17 | 38 |
| Race/Ethnicity, Customized: Unknown or Not Reported | Participants | 18 | 11 | 29 |
| Race/Ethnicity, Customized: White | Participants | 183 | 168 | 351 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 50 | 54 | 104 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 254 | 254 | 508 |
| Race/Ethnicity, Customized: Unknown or Not Reported | Participants | 19 | 10 | 29 |
6. Primary Endpoint
The registry lists the primary outcome as Physiologic BPD or Death by 36 Weeks PMA, measured over Randomization to 36 weeks PMA.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with physiologic BPD or death by 36 weeks PMA. It combines two outcomes: a diagnosis of physiologic BPD and death from any cause between randomization and 36 weeks PMA. An infant who dies before 36 weeks PMA is not assessed for BPD, but is included through the death component of the composite.
The registry describes BPD classification using existing NRN GDB criteria at 36 weeks PMA. For infants alive and in hospital, classification is based on respiratory status at 36 weeks PMA or a room-air weaning challenge performed between 36 and 37 weeks PMA. Infants transferred or discharged before 36 weeks are classified using the support they are receiving at that time. These rules make the endpoint a clinical classification tied to respiratory support and a specified assessment period, rather than a single laboratory measurement.
Composite outcomes can summarize whether any component occurred, but they do not show which component accounts for a group difference. Death and BPD are distinct outcomes, so component-specific results are important to interpretation. The registry record does not report primary outcome counts or an arm comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary question and gives the endpoint definition, but it does not report primary outcome counts by arm, an effect estimate, a confidence interval, or a p-value. The posted information therefore does not establish the direction or magnitude of the primary comparison, nor how precisely that comparison was estimated. No conclusion about whether the assigned treatment changed the composite outcome can be drawn from the endpoint description alone.
The endpoint is binary at the participant level: each infant is classified as having or not having physiologic BPD or death by 36 weeks PMA. For a binary outcome, an analysis may describe the event frequency in each arm and compare those frequencies using an effect measure such as a risk difference or risk ratio. These are general statistical concepts, not reported trial estimates. Without the arm-specific outcome data, neither the size nor the precision of such a contrast can be assessed.
The composite requires particular care. It counts either BPD or death, while the registry specifies that infants who die before 36 weeks PMA are not assessed for BPD. A composite result alone would not indicate whether its components contributed similarly or whether one component accounted for most of the observed pattern. Component outcomes are listed as secondary outcomes, but their results are not reported in the registry record.
The registry lists an intent-to-treat analysis population consisting of randomized infants who provided outcome data. That wording identifies an intended population but does not explain how infants without outcome data were handled, or how many had missing primary outcome information. Missingness can affect interpretation if outcome availability differs between assigned groups or is related to outcome status. The record does not report missing-data procedures or the amount of missing outcome information.
Other reported figures concern adverse events, not the primary endpoint. They should not be treated as substitute evidence for the primary comparison. The trial is listed as active, not recruiting, and the primary completion date is recorded as 2024-09-05, but the status and dates do not supply an outcome analysis. The registry record does not report the statistical analysis details needed to assess adjustment, model choice, or multiplicity handling.
9. Statistical Methods Explained
The registry identifies a randomized, masked, parallel-group trial and a binary primary endpoint. It does not report a complete statistical analysis plan or a primary outcome comparison. The explanations below describe general statistical ideas relevant to this design; they should not be read as a claim that a particular method was used for the trial.
What does randomization contribute?
In general, random assignment is intended to make treatment groups comparable at the time of allocation, apart from chance differences. It supports a comparison based on assigned treatment rather than a comparison formed after observing outcomes. Randomization does not guarantee that every baseline characteristic will be identical between groups, and it cannot prevent missing outcomes or problems with outcome assessment. The registry record does not describe the allocation-concealment process or report baseline comparisons.
How is a binary endpoint compared?
A binary endpoint records whether each participant experienced the defined event. General summaries can include the event count and the number assessed in each group. A risk difference expresses the contrast as a difference in event probabilities; a risk ratio expresses one probability relative to the other. A confidence interval describes the range of effect values compatible with the data and the analysis assumptions. Its width reflects statistical precision: a wider interval indicates greater uncertainty than a narrower one. None of these primary endpoint summaries is reported in the registry information.
Why does the composite definition matter?
The primary endpoint combines physiologic BPD and death by 36 weeks PMA. A composite can capture more than one clinically relevant event in a single outcome, but its overall result can be driven by one component more than another. The components may also differ in severity or meaning. General interpretation therefore considers component-specific results alongside the composite. Death by 36 weeks PMA, physiologic BPD, and BPD severity are among the secondary outcomes listed, but their results are not reported in the registry record.
What does the stated analysis population mean?
The registry describes an intent-to-treat analysis that includes randomized infants who provided outcome data. In general, an intent-to-treat approach aims to preserve the comparison created by random assignment, regardless of treatment received after assignment. The registry wording also conditions inclusion on having outcome data. It does not explain how outcomes unavailable for some randomized infants were handled, or report the extent and pattern of missingness. Those details are needed to judge the potential influence of missing data.
What can be said about planning assumptions?
The registry’s planning illustration is described as based on a stated fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration is not the trial’s design justification and is not observed power. In general, planning calculations show the sample size associated with specified assumptions about the effect to detect and the testing approach. They do not show the probability that the trial’s observed result is correct, and assumptions different from those used in planning can change the calculation. No numerical planning values or observed primary effect are reported in the information available for this analysis.
How should significance and uncertainty be read?
In general, a p-value evaluates how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the statistical test. It does not measure the probability that the null hypothesis is true, the clinical importance of an effect, or the probability that a finding will replicate. A confidence interval adds information about the range and precision of estimates. Because the registry record does not report a primary estimate, interval, or p-value, none of these interpretations can be applied to the trial’s primary comparison.
What is not documented?
The registry record does not report the primary outcome model or test, adjustment variables, handling of repeated or site-related structure, interim analyses, or procedures for multiplicity. Randomization, masking, and the endpoint definition do not establish which of those methods were used. These omissions limit the statistical detail that can be evaluated from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary composite outcome and secondary outcomes covering death by 36 weeks PMA, physiologic BPD, BPD severity, severe BPD, and use of additional postnatal steroids. The record does not report whether statistical testing across these outcomes was adjusted for multiplicity, whether any outcomes were designated for a particular testing sequence, or how secondary findings should be interpreted. Without a stated approach, isolated secondary comparisons should not automatically be treated as confirmatory evidence.
The primary outcome population is described as an intent-to-treat analysis including randomized infants who provided outcome data. The record does not report how many randomized infants lacked primary outcome data, why information was unavailable, whether missingness differed by arm, or what methods were used to handle missing outcomes. It also does not describe sensitivity analyses for missing data. These details matter because the observed participants may not represent all randomized infants if outcome availability is related to treatment assignment or outcome status.
The registry record does not provide the full analysis populations for secondary outcomes or clarify whether all analyses follow the same inclusion rule. It does not report interim analyses, stopping rules, or a statistical analysis plan. These matters are not inferable from the fact that the trial is randomized and masked. Accordingly, the extent to which multiplicity and missing-data risks were addressed is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| BUDE | 63 | 323 | 19.5% |
| SURF | 55 | 318 | 17.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BUDE | 49 of 323 |
| SURF | 42 of 318 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0.00% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BUDE | 232 of 323 |
| SURF | 187 of 318 |
Most frequent serious adverse event terms
| Event term | Organ system | BUDE | SURF |
|---|---|---|---|
| Haemorrhage intracranial | Nervous system disorders | 15 of 323 | 17 of 318 |
| Intestinal perforation | Gastrointestinal disorders | 14 of 323 | 6 of 318 |
| Hypotension | Vascular disorders | 13 of 323 | 7 of 318 |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | 8 of 323 | 8 of 318 |
| Hyperglycaemia | Metabolism and nutrition disorders | 8 of 323 | 3 of 318 |
| Sepsis | Infections and infestations | 6 of 323 | 2 of 318 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 2 of 323 | 6 of 318 |
| Pulmonary air leakage | Respiratory, thoracic and mediastinal disorders | 3 of 323 | 5 of 318 |
| Neonatal respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | 3 of 323 | 3 of 318 |
| Neonatal intestinal perforation | Gastrointestinal disorders | 0 of 323 | 4 of 318 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BUDE | SURF |
|---|---|---|---|
| Hyperglycaemia | Metabolism and nutrition disorders | 208 of 323 | 154 of 318 |
| Hypotension | Vascular disorders | 42 of 323 | 53 of 318 |
| Hypertension | Vascular disorders | 28 of 323 | 20 of 318 |
| Haemorrhage intracranial | Nervous system disorders | 20 of 323 | 17 of 318 |
| Sepsis | Infections and infestations | 6 of 323 | 5 of 318 |
| Pulmonary air leakage | Respiratory, thoracic and mediastinal disorders | 4 of 323 | 5 of 318 |
| Sepsis neonatal | Infections and infestations | 5 of 323 | 3 of 318 |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | 3 of 323 | 5 of 318 |
| Periventricular leukomalacia | Nervous system disorders | 5 of 323 | 2 of 318 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 5 of 323 | 2 of 318 |
Serious events with the highest arm-level rate: haemorrhage intracranial (5.3%), intestinal perforation (4.3%), hypotension (4.0%), pulmonary haemorrhage (2.5%), hyperglycaemia (2.5%).
The registry reports adverse-event group counts under the labels BUDE and SURF. For serious adverse events, the reported numbers at risk are 323 for BUDE and 318 for SURF; the numbers affected are 63 and 55, respectively. For other adverse events, the numbers at risk are 323 and 318, and the numbers affected are 232 and 187. The reported death counts are 49 for BUDE and 42 for SURF. These are counts as recorded, not rates calculated for comparison.
The registry also lists serious-event terms and percentages: haemorrhage intracranial, 5.3%; intestinal perforation, 4.3%; hypotension, 4.0%; pulmonary haemorrhage, 2.5%; hyperglycaemia, 2.5%; and pneumothorax, 1.9%. The record does not provide enough detail in the available information to assign these term percentages to a particular arm or to interpret them as a comparative treatment effect.
Adverse-event counts and event-term percentages answer different questions from the primary composite outcome. They should be read with attention to the group labels, the numbers at risk, and the distinction between participants affected and event terms reported. The registry record does not provide adjusted safety comparisons or further detail on overlap between event categories.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of budesonide with surfactant against surfactant alone, with physiologic BPD or death by 36 weeks PMA as the primary outcome. It supplies the endpoint definition and some adverse-event counts, but it does not report an arm-by-arm primary outcome result. As a result, the magnitude, direction, and precision of the primary comparison cannot be evaluated from the reported information.
The endpoint combines BPD and death. Even if a composite estimate were available, it would not by itself establish how each component contributed. The registry lists component-related secondary outcomes, but does not report their results. The primary outcome also depends on clinical classification of BPD using respiratory status, a room-air weaning challenge, or support status after transfer or discharge, according to the circumstances described in the record.
The enrollment entry and study dates describe the registry record, not the primary outcome findings. Likewise, adverse-event counts are safety information and do not replace an analysis of the primary outcome. Counts alone do not establish comparative risk or explain the uncertainty around a comparison.
In general, a treatment comparison is best understood using an effect estimate, its uncertainty, the analysis population, and details of missing outcomes and outcome assessment. Those statistical details are not reported for the primary outcome in the registry record. The available information therefore supports describing the trial question and design, but not a conclusion that the intervention did or did not change BPD or death.
13. Why This Trial Matters Statistically
This trial poses a focused statistical comparison in a population of extremely preterm infants: both groups receive surfactant, while the intervention group also receives budesonide. Randomization creates a framework for comparing outcomes by assigned group, and masking is intended to reduce the influence of knowledge of assignment on trial conduct or assessment. The registry identifies quadruple masking but does not specify which roles were masked.
The primary endpoint illustrates an important issue in neonatal trials: death can prevent assessment of a later morbidity outcome. Combining physiologic BPD and death defines an outcome that can be assessed even when an infant dies before BPD assessment, as the registry explicitly describes. At the same time, the composite requires component-specific interpretation so that a combined result is not mistaken for evidence about each component individually.
The BPD definition also draws on clinical status at a specified developmental time, with alternative classification rules for infants who are transferred or discharged earlier. This makes transparent outcome definitions and consistent application important to interpretation. The registry describes the classification approach, but does not report outcome results or details of assessor procedures.
Statistically, the record demonstrates why trial design information and outcome evidence are not interchangeable. Randomization, masking, and a defined endpoint explain how a comparison is structured; they do not reveal the estimated treatment effect or its precision. Without the primary outcome analysis, readers cannot assess the central comparative question from the registry record.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
A central limitation of the available registry information is that it does not report primary outcome counts by arm, an effect estimate, a confidence interval, or a p-value. It is therefore not possible to assess the observed primary comparison or its precision. The record also does not report results for the listed secondary outcomes, so component-specific interpretation of the composite is unavailable.
The primary analysis population is described as randomized infants who provided outcome data, but the handling and extent of missing outcomes are not reported. There is no reported account of missingness by arm, reasons for unavailable data, or sensitivity analyses. The record also does not provide detailed eligibility criteria, allocation concealment, masking roles, or assessor procedures beyond the stated BPD classification approach.
The registry record does not report the statistical model, adjustment strategy, multiplicity procedures, interim analyses, or a full statistical analysis plan. The enrollment entry is not accompanied by a reported sample-size justification. These details cannot be inferred from the Phase 3 designation or from the planning assumptions described for an illustration.
Safety information includes group counts and several event-term percentages, but the available information does not give comparative analyses or enough context to interpret all term percentages by arm. These limitations apply to interpretation of the registry record and do not establish whether further analyses exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Budesonide in Babies (BiB) Trial — NCT04545866.
- Registry record last updated 2026-04-15; status last verified 2026-04.
- Results first posted 2025-11-10.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The Budesonide in Babies Trial is a Phase 3 randomized, masked, parallel-group, active-controlled, multicenter study sponsored by the NICHD Neonatal Research Network. The registry lists enrollment as 642, status as active, not recruiting, a start date of 2021-04-01, and a primary completion date of 2024-09-05.
The intervention is budesonide mixed with surfactant, compared with surfactant alone. The primary endpoint is physiologic BPD or death by 36 weeks PMA. The registry describes the endpoint assessment and an intent-to-treat population of randomized infants with outcome data. It also lists secondary outcomes and reports adverse-event counts.
An arm-by-arm primary outcome result and its statistical uncertainty are not reported in the registry record. The available information therefore describes the trial design and question, but does not establish the primary comparative finding.