The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19) (NCT04389671), a na phase 2 study. The primary outcome is Oxygen Index (OI).

2. Clinical Question

The study is registered as a phase 2 study focused on safety and preliminary tolerability. Its primary endpoint is a short-term physiological measure rather than a comparison of outcomes between treatment groups. Oxygen Index combines mean airway pressure, inspired oxygen fraction and arterial oxygen pressure into an index intended to describe oxygenation support and oxygen use.

The registry describes lower Oxygen Index values as better, but that general direction does not establish what happened during this study. The registry record does not report a numerical change from baseline, a standard deviation for the change, or a comparison against an untreated or alternative-treatment group. It therefore does not provide a numerical answer about the observed trajectory of the primary outcome. The study’s single-group design also means that any change over time could not, by itself, distinguish an effect of lucinactant from other influences on participants’ condition or care.

3. Trial Design

This was a multicenter, single-treatment phase 2 study of lyophilized lucinactant in adults with COVID-19-associated acute lung injury. The registry lists an enrollment of 20 and a completed status. The start date is 2021-01-05, and the primary completion date is 2022-02-20. The intervention is described as lyophilized lucinactant reconstituted with sterile water for injection.

The design is recorded as single group, with allocation listed as NA and masking as none. No randomized control group is described. The registry’s note about the study design cautions that it is not a randomized comparison and that any arms should not be treated as a like-for-like control comparison. Consequently, the design is suited to describing what was measured in the treated group, but it does not provide a controlled estimate of the difference between lucinactant and another treatment or no study treatment.

The primary outcome population is listed as all participants who received study medication. The primary measure is change in Oxygen Index from baseline through 12 hours after initiation of dosing, summarized using a mean and standard deviation. Secondary outcomes include measures of inspired oxygen, arterial and pulse-oximetry oxygenation, oxygenation ratios, and carbon dioxide. The registry lists 20 outcome measures overall.

Although the study is marked completed, that status is not itself a report of the outcome findings. The registry record does not report numerical primary-endpoint results or analysis results. The protocol’s detailed dosing schedule, eligibility criteria, sample-size justification, and statistical analysis plan are not reported in the registry record. The record also does not report whether interim analyses were planned or performed.

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: No wash-out or run-in

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants that received study medication

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: One enrolled participant did not receive study treatment

6. Primary Endpoint

The registry lists the primary outcome as Oxygen Index (OI), measured over Baseline through 12 hours post initiation of dosing.

The primary endpoint is change from baseline in Oxygen Index, measured from baseline through 12 hours after initiation of dosing. The registry describes Oxygen Index as an index calculated from mean airway pressure multiplied by the fraction of inspired oxygen and 100, divided by the partial pressure of oxygen. The outcome is summarized by a mean and standard deviation, and its stated population is participants who received study medication.

In general, an index combining respiratory support and oxygenation measurements can provide a compact way to track physiological status. Mean airway pressure and inspired oxygen reflect aspects of respiratory support, while partial pressure of oxygen reflects oxygenation. The registry states that lower Oxygen Index values are better and gives a possible range of 0 to 1000; it also describes values under 25 as corresponding with a good outcome. These descriptions explain the intended direction and context of the measure, not the result observed in this study.

A change-from-baseline endpoint focuses on how a measure shifts over the specified observation period. Interpretation depends on the numerical change, its variability, the number of participants contributing data, and the handling of missing measurements. Those numerical endpoint results and analysis details are not reported in the registry record. Therefore, the endpoint definition alone does not establish whether the mean changed, how large any change was, or how precisely it was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

For a continuous measure such as Oxygen Index, a mean describes the average value or average change in the group being analyzed. A standard deviation describes how spread out individual measurements or changes are around that average. These statistics answer different questions: the mean concerns the group’s central value, while the standard deviation describes participant-to-participant variability. A standard deviation is not a confidence interval and does not, on its own, show how precisely the group mean has been estimated.

The registry says the primary endpoint is change from baseline and is measured using a mean and standard deviation. However, it does not provide the values. Without those estimates, readers cannot assess the direction or size of the average change, the spread of individual changes, or the precision of the average. The number of observations contributing to each assessment and the method used to calculate the change are also not reported in the registry record.

Why use change from baseline?

In general, a change-from-baseline outcome compares a participant’s follow-up measurement with that participant’s baseline measurement. This can focus attention on movement over time rather than only on the follow-up value. The interpretation still depends on how baseline and follow-up measurements were defined, whether measurements were available for the same participants, and how missing observations were handled. Those analysis details are not reported in the registry record.

The specified observation window runs from baseline through 12 hours after dosing begins. A short-term window defines when the primary outcome is assessed; it does not by itself describe longer-term outcomes. The registry lists other physiological measures, including Fraction of Inspired Oxygen, Partial Pressure of Oxygen, Oxygenation From Pulse Oximetry, Oxygen Index, Partial Pressure of Carbon Dioxide, End Tidal Carbon Dioxide, PaO2 to FiO2 ratio, and SpO2 to FiO2 ratio. These measures describe related but distinct aspects of oxygenation, respiratory support, or carbon dioxide. The registry lists 20 outcome measures overall, but does not report an analysis plan explaining how the measures were prioritized or interpreted together.

How should a confidence interval be understood?

In general, a confidence interval expresses statistical uncertainty around an estimate. A narrow interval indicates greater precision under the method’s assumptions, while a wide interval indicates less precision. A confidence interval is not the range containing every participant’s value, and it does not establish whether a finding is clinically important. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed from the registered outcome information.

What does the single-group structure allow?

The study is recorded as single group, with allocation listed as NA and masking as none. In general, a single-group study can describe measurements and events observed among participants receiving an intervention. It cannot produce a randomized between-group comparison when there is no randomized comparator. A before-and-after change, if reported, would describe a time pattern in the observed group; it would not alone demonstrate that the intervention caused the change. Other changes in illness or care could also contribute, and this design does not provide a concurrent randomized group to account for them.

The registry lists 20 enrolled participants and describes the primary population as participants who received study medication. The adverse-event record separately lists 19 at risk. Those values should not be assumed to be interchangeable: enrollment, receipt of medication, endpoint availability, and safety follow-up can define different analysis populations. The record does not report a participant flow accounting for those populations or explain why the listed safety population differs from enrollment.

What do the sample-size illustrations mean?

In general, a sample-size calculation estimates how many participants may be needed to detect a specified effect under chosen assumptions. The registry record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for a chosen power level; time-to-event illustrations are described in terms of total events.

These are planning illustrations, not the study’s actual design or observed power. This study is recorded as single group, so the equal-allocation, two-arm assumptions do not describe its treatment allocation. The sample-size justification used to design the trial is not reported in the registry record. The registry also does not report numerical endpoint results from which readers could judge an observed effect. Any planning illustration therefore should not be treated as evidence that the study was adequately powered or that an effect was observed.

What is not available about the analysis?

The registry lists zero analyses and does not report numerical results for the primary outcome. The statistical analysis plan, any adjustment for baseline values, the approach to repeated measurements, handling of outliers, missing-data methods, and any interim analyses are not reported in the registry record. These omissions limit the ability to evaluate the analysis beyond the endpoint definition and summary measure specified in the record. General statistical explanations cannot fill in those study-specific details.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Lyophilized Lucinactant")
n   <- c(19)
m   <- c(-0.91)
sp  <- c(3.14)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Lyophilized Lucinactant  19  -0.910  3.140  -2.423  0.603

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures, including several physiological measures related to oxygenation and carbon dioxide. When a study assesses multiple outcomes or time points, general statistical practice recognizes that the chance of finding an apparently notable result by chance can depend on how many comparisons are made and how they are selected. An analysis plan may specify a primary outcome, a testing hierarchy, or an adjustment strategy. Such a multiplicity strategy is not reported in the registry record. The primary outcome is identified, but no numerical analyses are listed, so the record does not show how results across the outcomes were interpreted.

The registry identifies participants who received study medication as the primary-outcome population. It does not report the number with usable endpoint measurements, the number assessed at each time point, or reasons for missing data. It also does not report how missing observations were handled, whether the analysis used only observed measurements, or whether any sensitivity analyses were performed. These details matter because the available measurements may not represent all participants equally if missingness is related to health status or other factors. That is a general concern, not a claim about why data may be missing in this study.

The registry record does not report a detailed analysis population definition beyond the stated primary population, nor does it provide a participant flow linking enrollment, treatment receipt, endpoint measurement, and safety follow-up. It does not report interim analyses, a prespecified statistical analysis plan, or any adjustment for multiplicity. With no numerical primary or secondary outcome analyses listed, it is not possible to assess how these issues affected the reported findings.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: septic shock (10.5%), atrial fibrillation (5.3%), cardiac arrest (5.3%), multiple organ dysfunction syndrome (5.3%), bacteraemia (5.3%).

The adverse-event record lists 19 participants at risk in the lyophilized lucinactant group. Serious adverse events affected 8 participants, other adverse events affected 16 participants, and 7 deaths are listed. The most frequently listed serious-event term is Septic Shock at 10.5%. Other listed terms are Atrial fibrillation at 5.3%, Cardiac arrest at 5.3%, Multiple organ dysfunction syndrome at 5.3%, Bacteraemia at 5.3%, and COVID-19 pneumonia at 5.3%.

These are descriptive observations in the study group. They do not establish that an event was caused by lucinactant, and the registry record does not provide a randomized control group for comparing event frequencies. The terms listed should not be interpreted as an exhaustive account of every event unless the record says so; the figures available describe the listed safety reporting. The registry also does not provide event timing, duration, severity grading beyond the serious-event classification, or participant-level overlap between categories. A participant may contribute to more than one event category, so these figures should not be added together to infer a total number of affected participants. The listed deaths likewise do not identify cause or establish treatment attribution.

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

The registry record establishes that a phase 2, multicenter, single-group study of lyophilized lucinactant was completed, with an enrollment of 20. It identifies change from baseline in Oxygen Index through 12 hours after dosing begins as the primary endpoint and describes the intended measure and direction. It also records adverse-event counts and terms in a safety group of 19 participants at risk.

Those details do not amount to a numerical report of the primary outcome. The record does not report the mean change in Oxygen Index, its standard deviation, a confidence interval, or a statistical test. It therefore does not show the size, direction, or precision of the average change. Descriptions of the index, including that lower values are better and the stated range of 0 to 1000, explain the measure but are not study findings.

The single-group design also cannot show how outcomes would have differed under a comparator condition. Even if a within-group change were available, it would describe what happened over time among observed participants rather than isolate a causal treatment effect. The registry does not report enough analysis information to assess missing measurements, outcome selection, multiplicity, or the treatment of repeated observations.

The safety counts describe events recorded in the treated group; without a like-for-like control comparison, they do not estimate comparative risk or establish causation. Completion status indicates the study is marked completed, not that all results are available in the registry record. The record supports a description of the study design, endpoint definition, and listed safety observations, but does not support conclusions about the magnitude or clinical importance of an endpoint effect.

14. Why This Trial Matters Statistically

This study is statistically notable because its registered primary question concerns a short-term physiological measure in a small, single-group study, while the registry record contains no numerical primary-endpoint analyses. That combination makes it important to separate the endpoint’s definition from evidence about its observed behavior. A measure can be clearly specified without the record providing the estimates needed to evaluate change or precision.

The design also illustrates the difference between describing change and estimating a comparative effect. A single-group study can collect repeated measurements and report safety events, but a time trend has no randomized control group to distinguish treatment-related change from other influences. This limitation is especially relevant when the target condition and the clinical care environment may change during observation; the registry’s design does not permit those influences to be separated through a randomized comparison.

The record lists multiple physiological outcomes and identifies one primary endpoint. A clear primary outcome can help focus interpretation, but the registry does not report a multiplicity strategy, the numerical outcome analyses, or how missing measurements were handled. Those omissions prevent readers from evaluating the relationship between the primary outcome and the other registered measures.

The safety record is also best understood as descriptive. It lists serious events, other events, and deaths among participants at risk, but does not provide a control group or establish causation. Taken together, the study record is useful for understanding the intended endpoint, study structure, and types of safety observations collected. It does not provide the numerical evidence needed to quantify primary outcome change or compare safety with another treatment condition.

15. 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 is that the registry record does not report numerical results for the primary endpoint, despite defining change in Oxygen Index as the main measure. Without the estimate and its variability, the direction, magnitude, and precision of any change cannot be evaluated. The record also does not report primary-outcome confidence intervals or statistical tests.

The study is single group, with allocation listed as NA and masking as none. There is no randomized comparator in the registry description, limiting causal interpretation and preventing a controlled estimate of treatment differences. The record’s own design note cautions against treating arms as like-for-like controls.

The record lists 20 enrolled participants, while the safety group lists 19 at risk. It describes the primary population as participants who received study medication but does not provide a participant flow or clarify endpoint availability. Reasons for any difference between enrollment, treatment receipt, outcome follow-up, and safety follow-up are not reported in the registry record.

The registry does not report the detailed protocol, eligibility criteria, dosing schedule, sample-size justification, statistical analysis plan, multiplicity strategy, missing-data methods, or interim-analysis procedures. It lists 20 outcome measures but no analyses. These omissions limit assessment of how outcomes were selected, how measurements were analyzed, and whether all planned results are represented. The adverse-event record is descriptive and does not establish event causation or comparative safety. These limitations are specific to what the registry record documents and should not be read as proof that unreported procedures or analyses did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19) — NCT04389671.
• Registry record last updated 2023-06-23; status last verified 2023-06.
• Results first posted 2023-06-23.
• 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.

19. Record Summary

NCT04389671 is a completed phase 2, multicenter, single-group study of lyophilized lucinactant in adults with COVID-19-associated acute lung injury. The registry lists enrollment of 20, no masking, and allocation as NA. The primary endpoint is change from baseline in Oxygen Index through 12 hours after dosing begins, summarized by a mean and standard deviation among participants who received study medication.

The registry record lists 20 outcome measures and no analyses. It does not report numerical primary-endpoint results, the statistical analysis plan, missing-data methods, or a sample-size justification. The safety group lists 19 participants at risk, with serious adverse events affecting 8, other adverse events affecting 16, and 7 deaths. These counts are descriptive and do not establish causation or a comparative safety effect.