Lucinactant for Treatment of Acute Hypoxemic Respiratory Failure in Children up to Two Years Old: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lucinactant for Treatment of Acute Hypoxemic Respiratory Failure in Children up to Two Years Old (NCT00578734), a randomized phase 2 study. The primary outcome is Duration of Mechanical Ventilation Through 14 Days.

2. Clinical Question

The clinical question concerns both safety and efficacy, according to the registry summary. The primary endpoint addresses the duration of ventilatory support; it is not itself a comprehensive measure of recovery or safety. The record also lists ventilator-free days and duration of oxygen use, intensive care unit stay, and hospitalization through 14 days as secondary outcomes. Numerical results for those secondary outcomes are not reported in the registry record.

The posted primary results are least-squares means in days, with a 95% confidence interval for each group. They describe estimated average duration in the trial groups; they do not show how long mechanical ventilation lasted for every individual child. The registry record does not report a numerical between-group estimate or a p-value for the primary comparison.

3. Trial Design

The registry identifies this as a phase 2, multicenter, randomized, masked, placebo-controlled, parallel-group trial. The trial evaluated intratracheal lucinactant against sham air placebo instillation in children up to two years old with acute hypoxemic respiratory failure. The record lists Windtree Therapeutics as sponsor and gives the enrollment as 165. Trial status is completed.

Randomization assigns participants to treatment groups by chance, which is intended to reduce systematic differences between groups at the start of a trial. Masking is intended to limit the influence of treatment knowledge on care, outcome assessment, or reporting. The record labels masking as triple, but does not report which roles were masked or how masking was maintained. The registry also does not report the randomization procedure, allocation ratio, or whether allocation was concealed.

The parallel design means participants were assigned to a group rather than being described as switching between treatments. The posted results include a lucinactant group of 84 and a sham air group of 81. These group counts are the denominators shown for the primary results and adverse-event summaries; the record does not explain any differences between outcome-specific analysis populations.

The registry reports trial start in 2007-06 and primary completion in 2010-04. It describes the primary efficacy analysis as intention-to-treat, including all randomized subjects, N=165. It also describes a supportive population of N=134 without a major protocol violation. Further details of the protocol, recruitment, randomization, masking, and the handling of deviations are not reported in the registry record.

The record says the sample-size calculation was based on historical data and an expected treatment effect. The detailed calculation, target effect, and other design assumptions are not reported in the registry record. This lack of detail means the posted design description cannot establish how the planned enrollment related to the precision of the primary estimate.

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

Analysis population for the primary outcome, as defined in the registry: The sample size calculation was based on historical data and expected treatment effect. The primary efficacy analysis was for the intent-to-treat population, defined as all randomized subjects (N=165). A supportive population (N=134) of subjects without a major protocol violation that could impact efficacy was also used for efficacy analyses.

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.

6. Primary Endpoint

The registry lists the primary outcome as Duration of Mechanical Ventilation Through 14 Days, measured over Up to 14 Days.

The primary endpoint is duration of mechanical ventilation from baseline to successful extubation, through a maximum of 14 days. Successful extubation is defined in the registry as not receiving mechanical ventilation for at least 24 hours. The unit is days, and the outcome is analyzed as a continuous measure using least-squares means.

Duration of ventilatory support is used to describe how long participants required mechanical ventilation over the specified follow-up period. A continuous endpoint retains information about differences in duration rather than reducing each participant's experience to a yes-or-no outcome. The 14-day limit defines the observation window; the endpoint does not describe duration beyond that window.

General statistical context: a least-squares mean is a model-based estimate of an average. It can account for variables included in the analysis model, but the registry record does not identify the model or any covariates. It should therefore not be assumed that the estimates are adjusted for particular baseline characteristics. The posted values are 4.0 days for lucinactant and 4.5 days for sham air, each accompanied by a 95% confidence interval.

This endpoint captures one aspect of the clinical course, not all relevant outcomes. It does not by itself summarize ventilator-free days, oxygen use, time in intensive care, hospitalization, adverse events, or survival. The registry lists some of those as secondary outcomes, but numerical results for them are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure: duration of mechanical ventilation in days. The registry reports a least-squares mean for each group and a 95% confidence interval. This presentation estimates an average duration while expressing uncertainty in that estimate. It is different from reporting a median, a range of individual values, or the proportion of participants reaching a particular event by a specified time.

What does a least-squares mean represent?

General statistical context: a least-squares mean is an estimated group average from a statistical model. Unlike a raw arithmetic mean, it can be adjusted for variables included in that model. That distinction matters because model-based estimates depend on the chosen model and its assumptions. The registry record does not report the model specification, any covariates, or whether the posted values are adjusted. The term alone does not reveal which, if any, participant characteristics were included.

How should the confidence intervals be read?

General statistical context: a confidence interval describes uncertainty in an estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The intervals reported for the group means are 3.5 to 4.6 days for lucinactant and 3.9 to 5.2 days for sham air. They do not describe the distribution of outcomes among individual children, and they are not a confidence interval for the treatment contrast.

For a formal comparison, the relevant quantity would ordinarily be an estimated difference between groups together with its uncertainty and an inferential test, if reported. The registry record does not report a numerical between-group estimate, its confidence interval, or a p-value for the primary endpoint. The means and their separate intervals should not be used to reconstruct those missing results. In particular, a comparison of separate intervals is not a replacement for an analysis of the contrast, which depends on the joint analysis and its assumptions.

Why does the endpoint definition matter?

The endpoint counts time from baseline until successful extubation, defined as not receiving mechanical ventilation for at least 24 hours, with observation limited to a maximum of 14 days. This definition specifies what event marks the end of the measured duration. It also sets a fixed follow-up window. General statistical context: clear event definitions and follow-up limits are important because different definitions of recovery or different observation periods can produce outcomes that are not directly comparable. The registry does not describe how events after the maximum follow-up window were handled beyond that limit.

What can be learned from the sample-size illustrations?

The trial's own sample-size calculation is described as based on historical data and an expected treatment effect, but the underlying inputs and detailed justification are not reported in the registry record. Separate planning illustrations use the observed effect and state assumptions of a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Such calculations describe hypothetical participant requirements under those assumptions for a future planning purpose. They are not an assessment of the probability that this completed trial found an effect, and they should not be called observed power.

General statistical context: planning calculations are sensitive to the effect size chosen, the variability assumed, the significance level, allocation, and the target power. Changing those assumptions changes the planning result. The registry record does not report the detailed basis for its own enrollment target, so the separate illustrations should not be read as reconstructing the original design decision. They also do not replace the observed group estimates or a confidence interval for the treatment contrast.

Why can continuous outcomes need careful distributional analysis?

General statistical context: a continuous duration measure may have a skewed distribution, and some participants may have particularly long or short durations. The choice of model, treatment of the follow-up limit, and handling of incomplete observations can affect estimated means and uncertainty. Over-dispersion, in general, means the observed variability is greater than a model assumes; if not accommodated, uncertainty may be understated. The registry record does not report diagnostic checks, distributional assumptions, or an approach to over-dispersion, so it is not possible to assess those choices from the posted record.

The record identifies a primary efficacy population and a supportive population, but does not provide the full statistical analysis plan. Details about covariate adjustment, handling of missing outcome data, protocol deviations, model diagnostics, and sensitivity analyses are not reported in the registry record. These omissions limit independent assessment of how the reported least-squares means were obtained, even though the estimates and intervals themselves are posted.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies duration of mechanical ventilation through 14 days as the primary outcome. It also lists ventilator-free days and duration of oxygen use, intensive care unit stay, and hospitalization through 14 days as secondary outcomes. The registry reports one posted secondary outcome measure, but numerical results for the listed secondary outcomes are not reported in the registry record.

Multiplicity arises when a trial evaluates multiple outcomes or makes multiple statistical comparisons. General statistical context: testing many hypotheses can increase the chance of at least one apparently unusual result unless the analysis plan accounts for the number and structure of tests. The registry record does not report a multiplicity adjustment, a hierarchy for secondary outcomes, or a broader statistical testing plan. It is therefore not possible to determine how the trial handled multiplicity or how any secondary findings would have been interpreted relative to the primary outcome.

The primary efficacy analysis is described as intention-to-treat, including all randomized subjects, N=165. A supportive population of N=134 without a major protocol violation is also described. The registry record does not report how missing outcome data were handled, whether all randomized participants contributed to the posted estimates, or how protocol deviations were classified. The posted arm-level counts are 84 for lucinactant and 81 for sham air, but the record does not give a participant-level accounting linking those counts to each analysis population.

There is no report of an interim analysis, a missing-data sensitivity analysis, or a prespecified method for censoring or imputation. Those methods are not reported in the registry record. Their absence from the record should not be treated as evidence that a method was or was not used. Without those details, readers cannot fully assess the robustness of the primary estimate to missing observations or analytic choices.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (6.0%), pneumothorax (6.0%), apnoea (2.5%), bradycardia (2.5%), endotracheal intubation complication (2.5%).

The registry reports serious adverse events in 20 of 84 participants in the lucinactant group and 14 of 81 participants in the sham air group. It also reports other adverse events affecting 65 of 84 participants in the lucinactant group and 62 of 81 participants in the sham air group. These are counts of affected participants against the group denominators reported for the safety summaries; they are not counts of every event episode.

The registry's listed serious adverse-event terms include Pneumonia at 6.0%, Pneumothorax at 6.0%, Apnoea at 2.5%, Bradycardia at 2.5%, Endotracheal intubation complication at 2.5%, and Laryngitis at 2.5%. The listing does not identify the treatment group for each term, so group-specific rates for these terms are not reported in the registry record. The record also does not report death counts.

General statistical context: adverse-event counts describe events recorded during the trial and are interpreted in light of the participants observed and the way events were defined and collected. The registry does not provide the full event definitions, duration of safety follow-up, or an analysis comparing groups. These counts should not be read as proof that an event was caused by a treatment or as a complete account of safety. No clinical advice or treatment conclusion follows from the counts alone.

12. What the Result Does, and Does Not, Mean

The posted primary results show least-squares mean duration of mechanical ventilation through 14 days of 4.0 days for lucinactant and 4.5 days for sham air. Their 95% confidence intervals are 3.5 to 4.6 days and 3.9 to 5.2 days, respectively. These figures describe estimated group averages and the uncertainty around each average under the analysis used.

They do not, by themselves, report the estimated difference between groups or the uncertainty around that difference. The registry record does not report a primary comparison estimate or p-value. The two group estimates should therefore not be translated into a claim about statistical significance or into a conclusion that one intervention did or did not have an effect. No new treatment-effect calculation is made from the posted group means.

The results also do not establish how the outcome was distributed among individual children. A group mean can conceal variation, and the record does not provide a standard deviation, median, or individual-level outcome distribution. The maximum follow-up of 14 days further limits what can be inferred about ventilation duration after that period.

The endpoint is one clinical measure among those named in the registry. Ventilator-free days, oxygen use, intensive care unit stay, and hospitalization are listed as secondary outcomes, but their numerical results are not reported in the registry record. The posted primary endpoint therefore cannot stand in for those outcomes or for all dimensions of safety and clinical course.

The safety summary reports serious and other adverse-event counts, along with a list of serious-event terms. The listing does not assign those terms to treatment groups, and death counts are not reported in the registry record. Those limitations prevent a complete group-specific interpretation of the listed events. The trial record supports a description of the posted estimates and counts, but not a broad conclusion about the overall balance of benefits and harms.

13. Why This Trial Matters Statistically

This trial illustrates why a posted outcome estimate and a formal treatment comparison are not interchangeable. The registry gives least-squares mean durations and confidence intervals for each group, which convey estimated averages and their precision. It does not report a numerical between-group contrast or its confidence interval. Statistical interpretation is consequently constrained: group-level figures are useful, but they do not provide every quantity needed to assess a comparative effect.

The endpoint also highlights how clinical definitions shape statistical outcomes. Duration of mechanical ventilation runs from baseline to successful extubation, defined as not receiving mechanical ventilation for at least 24 hours, and is observed through a maximum of 14 days. A stated event definition and time window make the target quantity clearer, while also setting boundaries on what that quantity represents.

The registry identifies an intention-to-treat efficacy population and a supportive population, but gives limited detail about the model, missing observations, and analysis choices. This is a practical reminder that an analysis label alone does not fully explain how estimates were produced. Model specification, population definitions, and handling of incomplete data all affect how readers assess precision and reproducibility.

Finally, the record lists safety events and secondary outcomes without reporting all corresponding comparative analyses or outcome results. That distinction matters: a registry can contain useful outcome definitions and counts while still leaving important interpretation details unreported. Careful reading separates what the record quantifies from what it does not establish, without treating absent information as a finding.

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 registry record leaves several trial-specific details unreported. Although the trial is described as multicenter, randomized, and triple masked, the sites, randomization method, allocation concealment, and masked roles are not specified. The protocol and full statistical analysis plan are not reported in the registry record, limiting assessment of prespecification and analytic decisions.

The primary results provide least-squares means and 95% confidence intervals by group, but no numerical treatment contrast, confidence interval for that contrast, or p-value. The model specification and covariates are also not reported. The relationship between the posted arm-level estimates and the described intention-to-treat and supportive populations is not fully explained in the registry record.

Outcome-level information is limited. Numerical results for the listed secondary outcomes are not reported in the registry record. The record does not describe missing-data methods, sensitivity analyses, distributional checks, or handling of the 14-day follow-up limit. It also does not provide measures of individual-level variability for the primary continuous outcome.

Safety information is similarly incomplete for interpretation: the event-term listing does not identify treatment groups, death counts are not reported, and details of event definitions and safety follow-up are not given. The sample-size calculation is described as based on historical data and expected treatment effect, but its detailed assumptions are not reported. These omissions do not show that the trial lacked such procedures or data; they indicate that those details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Lucinactant for Treatment of Acute Hypoxemic Respiratory Failure in Children up to Two Years Old — NCT00578734.
• Registry record last updated 2012-05-03; status last verified 2012-05.
• Results first posted 2012-04-27.
• 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.

18. Record Summary

NCT00578734 is a completed phase 2 randomized, triple-masked, parallel, placebo-controlled trial sponsored by Windtree Therapeutics. It evaluated intratracheal lucinactant against sham air in children up to two years old with acute hypoxemic respiratory failure. The registry gives enrollment as 165 and describes the primary efficacy population as all randomized subjects, N=165.

The primary endpoint was duration of mechanical ventilation from baseline to successful extubation, defined as not receiving mechanical ventilation for at least 24 hours, through a maximum of 14 days. The posted least-squares mean was 4.0 days for lucinactant, with a 95% confidence interval of 3.5 to 4.6, and 4.5 days for sham air, with a 95% confidence interval of 3.9 to 5.2.

The registry does not report a numerical primary treatment contrast or p-value. Secondary outcome results and several analysis details are not reported in the registry record. Serious adverse events affected 20 of 84 participants in the lucinactant group and 14 of 81 in the sham air group; the listed serious-event terms are not assigned to groups.