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 Anti-inflammatory Treatment at the Onset of Necrotizing Enterocolitis (NEC) in Preterm Infants (NCT01156480), a randomized na study. The primary outcome is CRP Level.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01156480 |
| Phase | NA |
| Condition | Necrotizing Enterocolitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 2 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Endeavor Health |
| Results posted | Yes |
2. Clinical Question
Population
Preterm infants diagnosed with stages II or III necrotizing enterocolitis (NEC) were the intended study population. The registry record says the study was terminated because enrollment was low after a drop in NEC incidence left very few eligible infants. It also notes that one enrolled infant was soon thought not to have NEC and never received study drug.
Intervention
The planned intervention was intravenous hydrocortisone, given on a staged dosing schedule. The registry description begins with 3mg/kg/day divided every 8 hours for 3 days, followed by lower daily doses. The full schedule is not reported in the registry record.
Comparator
The comparator was placebo, described as an equal volume administered on the same dosing schedule. The first study dose was intended within 6 hours of NEC diagnosis, after informed consent.
Primary question
The study planned to assess the effect of hydrocortisone on C-reactive protein (CRP), a marker of systemic inflammation, at 3 days. The registry record reports a CRP value for one participant in the placebo group and none in the hydrocortisone group, so it does not provide an estimable between-group comparison.
This was described as a pilot study, rather than a study with enough reported outcome data to establish a treatment effect. Its clinical question was whether an anti-inflammatory treatment started soon after diagnosis would alter an inflammation marker over the stated 3-day timeframe. The record does not report a numerical comparison, uncertainty interval, or test of the treatment contrast. Consequently, the posted outcome information cannot show whether CRP differed between groups, or how precisely any difference could be estimated.
3. Trial Design
The registry describes a randomized, parallel-group, quadruple-masked study comparing hydrocortisone with placebo in preterm infants with stages II and III NEC. The phase is listed as NA, and the study is marked terminated. The official title describes it as a pilot study. The registry enrollment is 2.
Random allocation is intended to assign participants to study groups by chance, helping avoid systematic differences between groups at the point of assignment. Masking is intended to limit the influence of treatment knowledge on care, outcome assessment, or reporting. The registry records quadruple masking, but does not specify in the information reported which roles were masked or how masking was maintained. These are general descriptions of the design terms, not additional details about how this trial was conducted.
The planned arms were hydrocortisone and placebo. The placebo was described as an equal volume given on the same schedule as hydrocortisone. The first dose was intended within 6 hours of diagnosis once informed consent had been obtained. The hydrocortisone description gives an initial dose of 3mg/kg/day divided every 8 hours for 3 days and then lists subsequent lower doses, but the full dosing schedule is not reported in the registry record.
The registry explains that the study ended because NEC incidence fell, leaving few eligible infants. It also states that one enrolled infant was subsequently thought not to have NEC and did not receive study drug. The results record reports 0 participants in the hydrocortisone arm and 1 in the placebo arm for the primary CRP outcome, despite registry enrollment of 2. These figures describe different parts of the record and should not be treated as a complete accounting of all enrollment and treatment disposition; further disposition details are not reported in the registry record.
The record does not report the sample-size justification, a detailed statistical analysis plan, or interim analyses. Those design details cannot be inferred from the randomized and masked structure 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.
Overall Study
| Stage | Hydrocortisone | Placebo |
|---|---|---|
| STARTED | 0 | 2 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Hydrocortisone | Placebo |
|---|---|---|
| change in diagnosis | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: This study was terminated due to low enrollment. We had a drop in our incidence of NEC, so there were very few eligible infants. One subject that was enrolled was soon thereafter thought NOT to have NEC, so that subject never received study drug.
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.
Population: premature neonates
| Characteristic | Unit | Hydrocortisone | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 1 | 1 | |
| Age, Categorical: <=18 years | Participants | — | 1 | 1 |
| Age, Categorical: Between 18 and 65 years | Participants | — | 0 | 0 |
| Age, Categorical: >=65 years | Participants | — | 0 | 0 |
| Sex: Female, Male: Female | Participants | — | 1 | 1 |
| Sex: Female, Male: Male | Participants | — | 0 | 0 |
| Region of Enrollment: United States | participants | — | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as CRP Level, measured over 3 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was CRP level, measured in mg/L, at 3 days. CRP is described in the registry as a non-specific marker of inflammation that is elevated in infants diagnosed with NEC. The investigators proposed tracking it as a marker of systemic inflammation following diagnosis and study treatment.
In general, a biomarker endpoint can provide a measurable indicator of a biological process over a defined timeframe. A marker is not itself a complete measure of a disease’s clinical course, and a change in a marker does not automatically establish a change in patient-important outcomes. The registry also lists clinical outcomes such as gastrointestinal failure, spontaneous intestinal perforation, gastrointestinal surgery, sepsis, time on parenteral nutrition, time to full enteral feeds, length of stay, and growth velocity.
The posted primary result is limited: the placebo group has 1 participant with a CRP value of 25.3 mg/L, while the hydrocortisone group has 0 participants with a reported value. No measure of spread is reported for the CRP result. With no reported hydrocortisone value, the registry record does not give a between-group estimate of the primary endpoint. The single observed value describes that recorded participant; it cannot characterize the distribution of CRP in the placebo group or support a comparative conclusion.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized pilot study intended to compare hydrocortisone with placebo for CRP level at 3 days in preterm infants diagnosed with stages II and III NEC. The posted primary outcome information is very sparse. It reports 0 participants with a primary CRP result in the hydrocortisone arm and 1 in the placebo arm. The placebo value is 25.3 mg/L. No spread estimate is reported, and the record does not provide a between-group effect estimate, confidence interval, or p-value.
This means the primary outcome results do not quantify how CRP differed between the assigned groups. A single value in one group, with no corresponding value in the other group, cannot establish the direction or magnitude of a treatment contrast. It also cannot show how variable CRP would have been among similar infants. The absence of a comparative estimate is a limitation of the available results, not evidence that the two treatments had the same effect.
The difference between registry enrollment and the primary outcome counts is important to the interpretation. Enrollment is listed as 2, while the primary outcome results list 0 for hydrocortisone and 1 for placebo. The registry narrative says one enrolled infant was later thought not to have NEC and did not receive study drug. It does not provide a complete participant flow that reconciles enrollment, eligibility, treatment assignment, treatment received, and outcome availability. Therefore, the outcome counts should be read as the numbers represented in the posted primary result, not as a full account of all trial activity.
The study was terminated because of low enrollment following a drop in NEC incidence and a resulting shortage of eligible infants. That explains why the record contains little outcome information, but it does not establish what the CRP result would have been with more participants. The planned comparison was randomized and masked, but those design features cannot compensate for the absence of outcome data in one arm.
The registry also records secondary outcomes, but numerical estimates for them are not reported in the registry record. The adverse-event data list 1 participant at risk in the placebo group and 0 in that group with a serious event; for other adverse events, the corresponding figures are also 1 and 0. The hydrocortisone group has 0 participants at risk in those entries. These small recorded counts do not support broad safety comparisons.
Overall, the posted findings document one placebo-group CRP observation and no hydrocortisone-group CRP observation. They do not estimate comparative efficacy or safety. The record does not report a sample-size justification or a statistical analysis plan, so it is not possible to determine from the registry whether the study was designed to estimate a particular effect with specified precision.
9. Statistical Methods Explained
The design is described as randomized, quadruple-masked, and parallel. In general, randomization assigns participants to groups by chance. Its purpose is to reduce the risk that treatment groups differ systematically at baseline, although randomization does not guarantee balance in a very small study. A parallel design assigns participants to one group and follows that group’s outcomes, rather than having each participant receive both treatments in sequence. Masking can reduce the influence of knowing the assigned treatment, but the registry does not report which people were masked or the procedures used to maintain masking.
What can a treatment comparison estimate?
In general, a randomized comparison aims to estimate how an outcome differs between the groups assigned to the intervention and comparator. For a continuous endpoint such as CRP, an analysis might compare group averages or another prespecified summary. The registry record does not report the planned summary measure or statistical model. It reports 0 participants for the hydrocortisone primary result and 1 for placebo, with a placebo CRP level of 25.3 mg/L. Those results do not allow a between-group estimate to be calculated or interpreted.
With only one observed value in a group, the data also cannot characterize within-group variability. No dispersion measure is reported. A standard error or confidence interval for a comparison would require enough information to quantify uncertainty and a defined analysis. Neither a confidence interval nor a p-value is reported for the primary comparison. The absence of these quantities should not be read as a precise estimate of no difference; there is no posted comparative estimate to assess.
How should a confidence interval be understood?
In general, a confidence interval presents a range of effect estimates compatible with the observed data and the assumptions of the statistical method. It communicates precision as well as the direction and scale of an estimated effect. A narrow interval indicates greater statistical precision than a wide interval, while an interval spanning effects in different directions can reflect substantial uncertainty. No confidence interval for the hydrocortisone-versus-placebo CRP comparison is reported in the registry record, so the precision of that comparison cannot be assessed.
What does low enrollment mean for inference?
In general, small amounts of outcome data make estimates unstable and leave limited information about variation between participants. In this record, the study enrollment is 2, and the primary outcome counts are 0 for hydrocortisone and 1 for placebo. The registry attributes termination to low enrollment after a drop in NEC incidence left very few eligible infants. The record also says that one enrolled infant was soon thought not to have NEC and did not receive study drug. These registry entries explain the limited posted results; they do not determine the treatment effect that would have been observed under fuller enrollment.
Sample-size planning and observed results are distinct. A planning calculation describes how many participants might be needed under specified assumptions to detect a target effect with a chosen error rate and power. It is not an observed result and does not indicate the power achieved by participants who actually enrolled. The registry record does not report the trial’s sample-size justification. No planning estimate is described as the study’s actual power.
Why does the analysis plan matter?
In general, a prespecified analysis plan clarifies the outcome summary, treatment comparison, handling of missing values, analysis population, and approach to multiple outcomes. These choices can affect the interpretation of results. The statistical analysis plan and any interim analyses are not reported in the registry record. It is therefore not possible to identify a planned model, covariate adjustment, or formal testing strategy from the trial description alone.
The record indicates that a two-arm comparison is not estimable for the posted count-type endpoint and that no analysis is reported. For the CRP endpoint, the specific obstacle is that there are no hydrocortisone outcome participants and just one placebo outcome participant in the posted results. No recalculated comparison is appropriate from those figures. There is also no discrepancy flagged between a sponsor analysis and a recalculation; no sponsor comparative estimate is reported to take precedence.
What is over-dispersion, in general?
Over-dispersion is a statistical concept for count outcomes: it occurs when the observed variability exceeds what a simple model assumes. If it is ignored, uncertainty estimates can be too small. That concept may matter for some count outcomes, but the registry information does not identify an analysis model for the listed secondary outcomes. It also does not report enough numerical data to assess over-dispersion. The primary endpoint is CRP level, and no group-level spread is available for evaluating its variability.
These general concepts help explain what would ordinarily be examined in a randomized trial analysis. They should not be mistaken for methods documented for this study. The registry record does not report a detailed statistical plan or an estimable primary treatment comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary endpoint of CRP level at 3 days and lists secondary outcomes that include gastrointestinal failure, spontaneous intestinal perforation, need for gastrointestinal surgery, incidence of sepsis, time on parenteral nutrition, time to full enteral feeds, length of stay, and growth velocity. Nine secondary outcomes are recorded as posted. Numerical results for those secondary outcomes are not reported in the registry record.
Multiplicity arises when several outcomes or statistical tests are examined. In general, testing many outcomes can increase the chance that at least one result appears notable by chance. A prespecified strategy can distinguish a primary test from secondary or exploratory analyses and can specify whether any adjustment is needed. The registry record does not report a multiplicity strategy, a family of planned tests, or an adjustment for multiple comparisons. It is therefore not possible to determine whether the planned analyses controlled the overall chance of false-positive findings.
Missing outcome information is central to interpreting this record. The posted primary results include no hydrocortisone participants and one placebo participant. The record does not report a complete flow of participants through eligibility, assignment, treatment, and outcome measurement, nor does it explain in detail the reasons for all absent outcome values. It states that one enrolled infant was subsequently thought not to have NEC and never received study drug. That narrative does not by itself specify how that infant was handled in any analysis.
Analysis populations, such as an intention-to-treat population or a treated-participant population, and the handling of missing outcomes are not reported in the registry record. No method for imputing missing values is reported. These omissions matter because different population definitions and missing-data assumptions can change the interpretation of a treatment comparison. With no reported hydrocortisone CRP outcome and no comparative analysis, there is no basis for judging how such choices affected an estimate.
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 |
|---|---|---|---|
| Placebo | 0 | 1 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Hydrocortisone | 0 of 0 |
| Placebo | 0 of 1 |
The registry reports adverse-event counts separately for serious and other adverse events. In the placebo group, 1 participant was listed as at risk for serious adverse events and 0 were listed as affected. For other adverse events, 1 participant was listed at risk and 0 affected. In the hydrocortisone group, 0 participants were listed at risk for either category, and 0 affected. Death counts are not reported in the registry record.
These are counts, not evidence that an event rate is zero in a broader population. The hydrocortisone group has no participants represented in these adverse-event entries, so the absence of recorded events there does not provide a comparison with placebo. Even the placebo observation is based on only 1 participant at risk. The registry does not report a comparative safety estimate or uncertainty interval.
In general, adverse-event counts require context, including how events were defined, the observation period, the number of participants exposed, and the completeness of event collection. The registry lists the counts but does not provide enough information to evaluate those features. The serious-event figures should therefore be read narrowly as the recorded counts for the participants at risk in the posted data, not as a reliable estimate of comparative safety.
12. What the Result Does, and Does Not, Mean
The result establishes that the registry contains a CRP value of 25.3 mg/L for 1 participant in the placebo group at the stated 3-day endpoint, and no participant with a reported primary CRP value in the hydrocortisone group. It also establishes that the study was terminated after low enrollment, which the record attributes to a drop in NEC incidence and very few eligible infants. One enrolled infant was later thought not to have NEC and did not receive study drug.
The result does not estimate the difference in CRP between hydrocortisone and placebo. It does not establish whether CRP was higher or lower in one group, how large a group difference might be, or how uncertain such a difference would be. A single placebo observation cannot describe the range of CRP values among eligible infants. With no hydrocortisone value, there is no observed comparison to interpret. This is not evidence of equivalence or evidence that there was no treatment effect.
The record also does not establish the effect of treatment on the listed clinical outcomes. Although secondary outcomes are identified, numerical results are not reported in the registry record. The adverse-event counts are similarly limited: the hydrocortisone group has no participants at risk in the posted entries, and the placebo group has 1 participant at risk with 0 affected for the listed categories. These data cannot support a broad comparison of risks.
Randomization and masking describe features of the intended study design, not the amount of information ultimately available. They do not make an incomplete comparison conclusive. Nor does the pilot-study label supply evidence of a particular treatment effect. The study’s low enrollment and the absence of a primary outcome in the hydrocortisone group leave the treatment question unanswered by the posted results.
Accordingly, the most defensible interpretation is descriptive: the registry records one placebo CRP value and no hydrocortisone CRP value, along with very limited safety counts. The record does not report the analysis plan, sample-size justification, or a numerical comparative estimate. No claim about treatment benefit, lack of benefit, or comparative safety can be drawn from these data.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it shows the difference between a carefully structured design and an informative set of results. Randomization, masking, and a parallel-group comparison can support strong inferences when enough outcome data are collected and analyzed. Here, the registry describes those design features, but the posted primary endpoint counts are 0 in the hydrocortisone group and 1 in the placebo group. The design alone cannot supply the missing comparison.
The record also illustrates why enrollment, treatment receipt, and outcome availability should be distinguished. Registry enrollment is 2, whereas the primary outcome results include one placebo participant and no hydrocortisone participants. The narrative notes that one enrolled infant was later thought not to have NEC and did not receive study drug. Without a complete participant flow, the reader cannot reconstruct every transition from enrollment to analysis. Clear reporting of those stages is important for understanding which participants contribute to each result.
A further statistical lesson is that an observed value and an estimated effect are not the same thing. The placebo CRP value of 25.3 mg/L is a recorded observation. It is not a group average comparison, and it does not indicate the amount of variation among participants. A comparative estimate and its precision require usable outcome data across the groups and a defined analysis.
The termination explanation matters as context, but it cannot substitute for results. Low enrollment after a drop in NEC incidence left few eligible infants, according to the registry. This helps explain why the trial did not yield a substantive comparison. It does not make the available result evidence for or against hydrocortisone, and it does not establish what a larger trial would have found.
Finally, the registry lists multiple secondary outcomes but does not report their numerical results or a multiplicity strategy. This underscores the importance of transparent outcome reporting and analysis plans, especially when a study includes several endpoints. The record offers a useful account of the intended question and the limits of the collected evidence, but not an answer to the treatment comparison.
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 most important trial-specific limitation is the very small amount of primary outcome information. Registry enrollment is 2, but the primary results report 0 hydrocortisone participants and 1 placebo participant. The only reported CRP value is 25.3 mg/L in the placebo group. No group spread or treatment contrast is reported, so the primary question cannot be answered from these results.
The registry states that the study was terminated because enrollment was low after a drop in NEC incidence left very few eligible infants. It also says one enrolled infant was soon thought not to have NEC and never received study drug. The record does not give a full participant flow to explain how each enrolled infant related to assignment, treatment, and endpoint reporting. This limits the ability to reconcile enrollment with the primary outcome counts.
The complete intervention schedule is not reported in the registry record. The hydrocortisone description gives an initial dose and subsequent lower daily doses but ends before the full schedule is stated. The placebo description likewise does not provide a complete treatment duration in the reported text. Masking is described as quadruple, but the identities of masked roles and the masking procedures are not specified.
The registry does not report a sample-size justification, detailed statistical analysis plan, interim analyses, analysis populations, missing-data procedures, or multiplicity strategy. Numerical results for the listed secondary outcomes are not reported in the registry record. Death counts are also not reported. These omissions prevent evaluation of planned precision, handling of absent outcomes, and the scope of any formal comparisons.
These limitations are specific to the information recorded for this study. They mean that the results support only a narrow description of the posted observations and do not permit a reliable assessment of comparative CRP outcomes or safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Anti-inflammatory Treatment at the Onset of Necrotizing Enterocolitis (NEC) in Preterm Infants — NCT01156480.
- Registry record last updated 2020-09-09; status last verified 2020-08.
- Results first posted 2014-03-24.
- 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 registry describes a randomized, quadruple-masked, parallel pilot study of hydrocortisone versus placebo in preterm infants with stages II and III NEC. The primary endpoint was CRP level in mg/L at 3 days. The study is marked terminated, with low enrollment attributed to a drop in NEC incidence and very few eligible infants.
Registry enrollment is 2. For the primary endpoint, the hydrocortisone group has 0 participants and the placebo group has 1, with a reported CRP value of 25.3 mg/L. The registry notes that one enrolled infant was later thought not to have NEC and did not receive study drug. No between-group estimate or uncertainty interval is reported.
Secondary outcomes are listed, but their numerical results are not reported in the registry record. Adverse-event entries report 0 affected among 1 participant at risk in the placebo group and no participants at risk in the hydrocortisone group. The available results are descriptive and do not establish a comparative treatment effect.