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 Hydrocortisone for BPD (NCT01353313), a randomized phase 3 study. The primary outcome is Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01353313 |
| Phase | Phase 3 |
| Condition | Infant, Newborn, Infant, Small for Gestational Age, Infant, Very Low Birth Weight |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 800 |
| Arms in the primary outcome | n/a |
| Lead sponsor | NICHD Neonatal Research Network |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned infants born before 30 weeks of gestational age who were intubated at 14–28 days of life. The primary-outcome analysis population is described as randomized infants with outcome data available at hospital discharge. The registry record does not give further eligibility details or explain how infants without available discharge data were handled.
Intervention
The intervention was a 10-day course of hydrocortisone. The registry describes hydrocortisone sodium succinate for intravenous administration, reconstituted with unpreserved normal saline. The registry record does not report the dose or schedule in the information available for this analysis.
Comparator
The comparator was saline placebo. The registry describes random assignment to hydrocortisone or placebo and lists triple masking. Further details about who was masked and how masking was maintained are not reported in the registry record.
Primary question
The primary question was whether infants survived without moderate or severe physiologic bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. The registry defines moderate or severe physiologic BPD by a need for supplemental oxygen and/or positive airway pressure to maintain oxygen saturation greater than 90 percent. Although the trial’s stated objective is clear, the registry record does not report the primary outcome counts, an effect estimate, a confidence interval, or a significance test.
3. Trial Design
The registry describes a phase 3, randomized, parallel-group trial comparing hydrocortisone with saline placebo. The study is listed as triple-masked. The record does not specify which groups of people were masked, the randomization procedure, or whether allocation was concealed; those details are not reported in the registry record.
The target population was intubated infants born before 30 weeks of gestational age. The brief summary places treatment at 14–28 days of life and describes a 10-day course. The listed enrollment is 800. That registry value describes enrollment, but it does not establish how many participants contributed data to each outcome or analysis.
The primary outcome concerns survival without moderate or severe physiologic BPD at 36 weeks postmenstrual age. Other listed outcomes include successful extubation, deaths before discharge, BPD grade at 36 weeks, duration of mechanical ventilation and oxygen supplementation, hospital stay among survivors, dexamethasone use, and neurodevelopmental impairment categories. The record also describes an interest in neurodevelopmental outcomes at 22–26 months corrected age.
The trial is marked completed, with a start date of 2011-08-11 and a primary completion date of 2020-09-21. These administrative details do not indicate when each outcome was assessed or when results were analyzed. A detailed statistical analysis plan, the planned methods for estimating treatment effects, and the basis for the enrollment target are not reported in the registry record.
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.
Overall Study
| Stage | Hydrocortisone | Placebo |
|---|---|---|
| STARTED | 398 | 402 |
| Completed Assessment for Neurodevelopmental Impairment | 321 | 318 |
| Died After Discharge | 8 | 6 |
| Died Before Discharge | 35 | 40 |
| Survived to Discharge | 363 | 362 |
| COMPLETED | 364 | 364 |
| NOT COMPLETED | 34 | 38 |
Reasons for not completing this period:
| Reason | Hydrocortisone | Placebo |
|---|---|---|
| Lost to Follow-up | 22 | 23 |
| Incomplete Follow-up or No Study Data | 12 | 15 |
Analysis population for the primary outcome, as defined in the registry: The analysis population includes all randomized infants with available data at hospital discharge.
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 | Hydrocortisone | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 398 | 402 | 800 | |
| Age, Continuous | weeks | 24.9 (SD 2) | 24.9 (SD 2) | 24.9 (SD 2) |
| Sex: Female, Male: Female | Participants | 212 | 167 | 379 |
| Sex: Female, Male: Male | Participants | 186 | 235 | 421 |
| Race/Ethnicity, Customized: Black | Participants | 139 | 168 | 307 |
| Race/Ethnicity, Customized: Missing | Participants | 10 | 11 | 21 |
| Race/Ethnicity, Customized: Other | Participants | 18 | 17 | 35 |
| Race/Ethnicity, Customized: White | Participants | 231 | 206 | 437 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 66 | 60 | 126 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 326 | 337 | 663 |
| Race/Ethnicity, Customized: Unknown or Not Reported | Participants | 6 | 5 | 11 |
| Infant Body Weight | grams | 710.3 (SD 162.7) | 720.4 (SD 171.8) | 715.4 (SD 167.3) |
| Maternal Education: College degree/more | Participants | 66 | 69 | 135 |
| Maternal Education: High school degree | Participants | 101 | 108 | 209 |
| Maternal Education: Less than High school degree | Participants | 68 | 59 | 127 |
| Maternal Education: Partial college | Participants | 78 | 85 | 163 |
| Maternal Education: Unknown | Participants | 85 | 81 | 166 |
6. Primary Endpoint
The registry lists the primary outcome as Survival Without Moderate/Severe Physiologic Bronchopulmonary Dysplasia (BPD), measured over From day of randomization to 36 weeks post menstrual age.
| 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 who survived without moderate or severe physiologic BPD at 36 weeks postmenstrual age. It combines survival and respiratory status into a single outcome: a participant must be alive and meet the stated criteria for absence of moderate or severe physiologic BPD to count as having the favorable endpoint.
The registry defines moderate or severe physiologic BPD as requiring supplemental oxygen and/or positive airway pressure to maintain oxygen saturation greater than 90 percent. A room air challenge was performed for infants estimated to receive less than 0.30 FiO2 by nasal cannula. The record does not provide additional details about adjudication or assessment procedures.
As a general statistical point, a combined endpoint can capture more than one clinically relevant aspect of an infant’s status in a single measure. Its interpretation depends on the exact definitions of its components and on how often each component occurs. A combined outcome does not, by itself, show whether any observed difference is driven by survival or by respiratory status. Here, the registry record does not report the component counts or the primary endpoint result, so the comparative outcome cannot be interpreted from this record alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record states the primary outcome and the analysis population, but it does not post the primary outcome counts or a comparison between randomized groups. It also does not report an effect estimate, confidence interval, or p-value for survival without moderate or severe physiologic BPD. Consequently, the direction, magnitude, and precision of any primary-outcome difference are not reported in the registry record. The trial’s stated objective should not be mistaken for a reported finding.
The outcome is defined at 36 weeks postmenstrual age and combines survival with respiratory criteria. The record says the analysis population includes all randomized infants with available data at hospital discharge. That wording does not mean that every randomized infant necessarily contributed an observed endpoint. The number with available outcome data and the handling of unavailable data are not reported in the registry record.
The registry lists multiple secondary outcomes, including extubation, death before discharge, BPD grade, respiratory support measures, hospital stay, dexamethasone use, and neurodevelopmental impairment categories. The existence of these measures does not establish that results for them are posted, nor does it show which analyses were prespecified. The record lists 40 outcome measures and zero analyses. The results presented in the record are therefore insufficient for a statistical comparison of the primary outcome or for judging how secondary outcomes relate to it.
Serious and other adverse-event counts are posted separately by group. These counts describe events recorded in the registry; without a comparative analysis, adjustment details, or further context, they do not establish whether group differences are statistically meaningful. The listed deaths are also safety information and should not be treated as a substitute for the primary composite outcome.
In general, statistical interpretation considers both the estimated effect and its uncertainty. A confidence interval indicates a range of values compatible with the data under the analysis assumptions; it does not guarantee that the true effect lies within that range. Because no primary effect estimate or interval is reported in the registry record, its precision cannot be assessed. No conclusion about benefit or lack of benefit follows from the absence of posted results.
9. Statistical Methods Explained
What does randomization contribute?
The registry identifies the study as randomized, with a parallel comparison between hydrocortisone and saline placebo. In general, random assignment is intended to make treatment groups comparable, on average, with respect to characteristics that could affect outcomes. It does not ensure that groups are identical, especially for any particular characteristic, and the strength of the comparison still depends on how participants are followed and analyzed. The registry record does not report the sequence-generation method, allocation concealment, or detailed analysis procedures.
What does masking mean in this record?
The study is listed as triple-masked. Masking is a general design approach intended to limit the influence of knowledge about treatment assignment on care, assessment, or reporting. The label alone does not identify which people were masked or how masking was maintained. Those details are not reported in the registry record, so the practical implications of the masking designation cannot be assessed further.
How should the primary endpoint be understood?
The primary measure is a participant count for survival without moderate or severe physiologic BPD at 36 weeks postmenstrual age. It is a binary outcome at the participant level: each infant either meets the combined endpoint definition or does not. In general, binary outcomes can be described using counts and proportions, followed by an effect measure and uncertainty interval. No such primary-outcome comparison is reported in the registry record, and no additional calculation can replace the missing trial analysis.
The endpoint’s definition includes oxygen and/or positive airway pressure requirements, an oxygen saturation threshold, and a room air challenge for infants meeting the stated FiO2 condition. These rules help define the outcome, but do not provide the observed number of infants meeting it. The record does not report how outcome assessors applied the criteria or whether outcome adjudication was independent.
What does a confidence interval communicate?
As a general statistical explanation, a confidence interval describes uncertainty around an estimate under a specified method and its assumptions. A narrower interval indicates greater precision than a wider interval for the same type of estimate, but interval width alone does not determine clinical importance. Whether an interval includes a value representing no difference depends on the effect measure being used. Because the registry record posts no primary effect estimate or confidence interval, neither the estimated size nor its precision can be assessed.
What can a p-value establish?
In general, a p-value describes how compatible the observed data are with a specified null hypothesis under the statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A p-value is most interpretable alongside the estimate, interval, outcome definition, and analysis plan. The registry record does not report a primary p-value or identify a primary-outcome testing procedure.
What is known about sample-size planning?
The registry describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm; time-to-event illustrations use a total event count. These assumptions describe the illustration, not necessarily the trial’s original design. The trial’s own sample-size justification and design assumptions are not reported in the registry record. Planning illustrations are not observed power and cannot establish whether a study has a particular probability of detecting an effect after its results are known.
Why do analysis populations matter?
The record says the primary analysis population includes all randomized infants with available data at hospital discharge. This describes a restriction based on outcome availability, rather than establishing that every randomized infant was included in every analysis. In general, missing outcome data can affect both the number of observations and the interpretation of a comparison. The consequences depend on how much data are missing, why they are missing, and the assumptions used to address them. The registry record does not report the amount of missing primary-outcome data or the methods used to handle it.
More broadly, these statistical concepts explain how a trial result might be assessed; they do not fill gaps in the registry record. Without the primary group counts, analysis methods, estimate, and uncertainty measure, the primary comparison cannot be reconstructed from the posted information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 40 outcome measures, including the primary outcome and several measures of respiratory status, survival, hospital course, and neurodevelopment. It lists zero analyses. The number of listed measures does not establish how many hypothesis tests were conducted, and the record does not report whether secondary outcomes were tested, designated as exploratory, or adjusted for multiplicity.
As a general statistical point, when many outcomes or comparisons are tested, the chance of obtaining at least one apparently notable result can increase. Methods to address this issue depend on the prespecified testing strategy and the scientific questions. No multiplicity procedure or hierarchical testing plan is reported in the registry record. It is therefore not possible to determine how the trial’s reported or unreported comparisons were intended to be interpreted as a set.
The primary-outcome population is described as all randomized infants with available data at hospital discharge. The record does not report how many randomized infants lacked primary-outcome data, reasons for missingness, or any imputation or sensitivity analyses. It also does not report whether the same analysis population was used for each secondary outcome. In general, missingness can affect precision and may bias a comparison if availability is related to outcome or treatment in ways not handled by the analysis. The relevant patterns and methods are not reported in the registry record.
These omissions limit assessment of both the reliability of individual comparisons and the broader pattern across outcomes. The registry record does not provide enough information to infer a missing-data strategy or multiplicity adjustment.
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 |
|---|---|---|---|
| Hydrocortisone | 84 | 398 | 21.1% |
| Placebo | 95 | 402 | 23.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Hydrocortisone | 43 of 398 |
| Placebo | 46 of 402 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0.05% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Hydrocortisone | 106 of 398 |
| Placebo | 95 of 402 |
Most frequent serious adverse event terms
| Event term | Organ system | Hydrocortisone | Placebo |
|---|---|---|---|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 61 of 398 | 61 of 402 |
| Nosocomial infection | Infections and infestations | 32 of 398 | 29 of 402 |
| Hyperglycaemia | Metabolism and nutrition disorders | 28 of 398 | 19 of 402 |
| Intestinal perforation | Gastrointestinal disorders | 9 of 398 | 13 of 402 |
| Adrenal insufficiency neonatal | Congenital, familial and genetic disorders | 5 of 398 | 16 of 402 |
| Hypertension | Vascular disorders | 15 of 398 | 4 of 402 |
| Pneumonia | Infections and infestations | 6 of 398 | 2 of 402 |
| Necrotizing enterocolitis neonatal | Gastrointestinal disorders | 2 of 398 | 5 of 402 |
| Patent ductus arteriosus | Congenital, familial and genetic disorders | 1 of 398 | 4 of 402 |
| Sepsis neonatal | Infections and infestations | 2 of 398 | 3 of 402 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Hydrocortisone | Placebo |
|---|---|---|---|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 41 of 398 | 48 of 402 |
| Hypertension | Vascular disorders | 56 of 398 | 29 of 402 |
| Adrenal insufficiency neonatal | Congenital, familial and genetic disorders | 22 of 398 | 24 of 402 |
| Nosocomial infection | Infections and infestations | 18 of 398 | 27 of 402 |
| Hyperglycaemia | Metabolism and nutrition disorders | 25 of 398 | 12 of 402 |
| Sepsis neonatal | Infections and infestations | 5 of 398 | 7 of 402 |
| Hyperkalemia | Metabolism and nutrition disorders | 5 of 398 | 6 of 402 |
| Intestinal perforation | Gastrointestinal disorders | 5 of 398 | 5 of 402 |
| Hyponatremia | Metabolism and nutrition disorders | 4 of 398 | 2 of 402 |
| Pneumonia | Infections and infestations | 1 of 398 | 3 of 402 |
Serious events with the highest arm-level rate: respiratory failure (15.3%), nosocomial infection (8.0%), hyperglycaemia (7.0%), adrenal insufficiency neonatal (4.0%), hypertension (3.8%).
The registry lists serious adverse-event counts for 398 participants at risk in the hydrocortisone group, with 84 affected, and for 402 participants at risk in the placebo group, with 95 affected. For other adverse events, the corresponding counts are 106 of 398 and 95 of 402. Deaths are listed as 43 in the hydrocortisone group and 46 in the placebo group. These are posted counts, not a comparative statistical analysis.
The registry also lists serious adverse-event terms with percentages: respiratory failure, 15.3%; nosocomial infection, 8.0%; hyperglycaemia, 7.0%; adrenal insufficiency neonatal, 4.0%; hypertension, 3.8%; and intestinal perforation, 3.2%. The record does not specify the denominator or provide group-specific percentages for these terms, so they should not be assigned to one treatment group based on this listing.
In general, adverse-event counts require context about definitions, observation periods, and participants at risk. The registry record does not report a detailed comparative safety analysis or the methods used to assess these events. The counts alone do not establish a causal relationship or the statistical significance of any difference.
12. What the Result Does, and Does Not, Mean
The registry record identifies a randomized comparison of hydrocortisone and saline placebo and specifies a primary endpoint focused on survival without moderate or severe physiologic BPD at 36 weeks postmenstrual age. It also lists secondary respiratory, survival, hospital-course, and neurodevelopmental outcomes, along with adverse-event counts. These details describe the trial’s questions and some posted safety information.
However, the primary outcome results are not reported in the registry record. There are no primary group counts, treatment-effect estimate, confidence interval, or p-value in the information available for this analysis. The record therefore does not establish the direction or magnitude of a primary-outcome difference, or how precisely it could be estimated. A stated objective is not evidence that the objective was met.
The listed adverse-event figures should also be read within their limits: they are counts, not adjusted comparisons, and the record does not provide group-specific results for the serious-event terms. These figures do not replace the primary endpoint or resolve the missing efficacy results.
As a general statistical principle, absence of a reported result is not evidence that groups were the same, nor is it evidence that one group did better. It means the relevant comparison cannot be evaluated from the registry record. The record does not report the detailed statistical analysis plan, missing-data methods, or multiplicity approach needed to assess those aspects of the trial.
Accordingly, the information supports a description of the design, outcome definition, analysis population wording, and posted adverse-event counts. It does not support a conclusion about whether hydrocortisone changed survival without moderate or severe BPD or any other clinical outcome.
13. Why This Trial Matters Statistically
This trial poses a statistical question involving both survival and respiratory status in a defined group of intubated infants born before 30 weeks of gestational age. Combining survival with a physiologic BPD definition makes the endpoint important to interpret carefully: the result would depend on both components and on consistent application of the respiratory criteria.
The randomized, parallel-group design and listed masking are relevant features for understanding how the comparison was intended to be conducted. The record also identifies several secondary outcomes spanning extubation, respiratory support, hospital stay, and later neurodevelopment. Considering outcomes across different time points can describe different aspects of the clinical course, but it also makes clear why prespecified analysis and multiplicity procedures matter. Those procedures are not reported in the registry record.
Statistically, a clear endpoint definition is only one part of an interpretable trial result. Readers also need group-level outcome data, an effect estimate, a measure of uncertainty, and an account of missing data and analysis choices. Here, the registry record describes the primary endpoint but does not report its comparative results. That distinction is central: the study’s question is documented, while its answer cannot be evaluated from the posted primary-outcome information.
The posted adverse-event counts add safety information, but without further comparative methods they should not be treated as definitive evidence about differences between groups. This record is therefore a useful example of why design details and outcome definitions cannot substitute for complete, interpretable results.
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.
The main limitation for statistical interpretation is that primary-outcome results are not reported in the registry record. No group counts, effect estimate, confidence interval, or p-value is available for survival without moderate or severe physiologic BPD. The registry lists 40 outcome measures but zero analyses, so results for the listed secondary measures cannot be assessed from the analysis information.
The primary analysis population is described as randomized infants with available data at hospital discharge, but the number of infants with data, the number without data, and reasons for any missing outcomes are not reported. The record does not describe imputation, sensitivity analyses, or whether each outcome used the same population. The effect of missing data on the comparison therefore cannot be evaluated.
The registry record does not report the statistical analysis plan, the trial’s sample-size justification, or its approach to multiple outcomes. Although a planning illustration is described, the record does not establish that its assumptions were the assumptions used for the trial’s original design. Randomization and triple masking are listed, but procedural details about allocation and masking are not reported.
For safety, group-level counts are posted, but details needed to interpret the listed serious-event terms, including their denominator and group-specific percentages, are not reported. No comparative safety analysis is given. These trial-specific gaps limit assessment of both the primary outcome and the broader balance of outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Hydrocortisone for BPD — NCT01353313.
- Registry record last updated 2025-02-27; status last verified 2025-02.
- Results first posted 2022-08-19.
- 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
NCT01353313 is listed as a completed phase 3 randomized, parallel-group trial of hydrocortisone versus saline placebo in intubated infants born before 30 weeks of gestational age. The registry lists enrollment of 800, triple masking, and a 10-day treatment course. Its primary outcome is survival without moderate or severe physiologic BPD at 36 weeks postmenstrual age, among randomized infants with available data at hospital discharge.
The registry lists secondary respiratory, survival, hospital-course, and neurodevelopmental outcomes. It also posts serious and other adverse-event counts and deaths by group. The primary outcome comparison, detailed statistical analysis methods, missing-data methods, and multiplicity strategy are not reported in the registry record.