A Safety and Efficacy Study of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks Gestational Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Efficacy Study of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks Gestational Age (NCT04264156), a randomized phase 2 study. The primary outcome is Number of Participants With Respiratory Failure or Death.

2. Clinical Question

The study’s stated purpose was to evaluate safety and efficacy for lucinactant used in conjunction with nCPAP, compared with nCPAP alone. Its brief summary also describes interest in the incidence of and time to respiratory failure and/or death during the first 72 hours and 28 days of life. The posted primary outcome, however, is a count of participants with respiratory failure or death at the 28-day timeframe. It does not report a time-to-event estimate.

For the primary outcome, the posted count is 6 participants in the lucinactant-plus-nCPAP arm and 0 in the nCPAP-only arm. These counts are accompanied by very different arm sizes: 11 and 1, respectively. In particular, the comparator count describes only one participant. These data frame the clinical question but do not support a precise comparative estimate. The registry record does not report an inferential analysis for the primary outcome.

3. Trial Design

The registry record describes a Phase 2, randomized, parallel-group, triple-masked, controlled study. Its official title characterizes the study as multinational and multicenter. The planned comparison was inhaled lucinactant with nCPAP versus nCPAP alone in preterm neonates 26 to 32 weeks gestational age with RDS. The brief summary says half of the participants would receive each approach, while the posted enrollment and arm counts are 12 overall, 11 in the lucinactant arm, and 1 in the nCPAP-only arm.

The lucinactant arm received 160 mg total phospholipids per kilogram as an aerosol once. Up to 3 repeats of 80 mg/kg were allowed within 36 hours of birth. The comparator is described as nCPAP only and as a sham comparator; bubble nCPAP is identified as standard of care. The record states that treatment time behind a barrier was intended to match the active treatment delivery time. Details about which parties were masked, how masking was maintained, and whether masking was assessed are not reported in the registry record.

The study started on 2020-04-18, and its primary completion date is 2021-01-31. Its status is terminated. The reason for termination, the timing of termination relative to enrollment, and whether termination was related to safety, recruitment, or another consideration are not reported in the registry record. The record does not give recruitment by site or country, or explain why the observed arm sizes differed from the half-and-half allocation described in the study summary.

The stated primary outcome is the number of participants with respiratory failure due to RDS or death through 28 days of life. The primary outcome population is Intent-to-Treat. Three secondary outcomes are listed: BPD, mortality, and common complications of prematurity. The registry record does not report the planned sample-size justification, the allocation method beyond randomization, or a detailed statistical analysis plan.

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: Subjects were screened before enrollment. Screen fail reasons included: unable to maintain required FiO2 (majority of screen fails), no determination of RDS, need for mechanical ventilation, outside of enrollment window

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat

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: Intent-to-Treat

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Respiratory Failure or Death, measured over 28 days of life.

The primary outcome is a participant count: the number of participants with respiratory failure due to RDS or death by 28 days of life. The record defines respiratory failure due to RDS as intubation for mechanical ventilation and/or surfactant administration. The stated timeframe is 28 days of life, and the population is Intent-to-Treat.

A combined outcome can capture more than one clinically important event in a single endpoint. In this case, it includes respiratory escalation represented by intubation and/or surfactant administration, as well as death. The count therefore reflects whether a participant met the registry definition at any point in the specified timeframe, rather than how long the participant remained event-free or the number of episodes. This is a general description of how a binary participant-level outcome is read; the registry record does not provide additional rationale for selecting this endpoint.

The posted counts are 6 of 11 participants in the lucinactant-plus-nCPAP arm and 0 of 1 in the nCPAP-only arm. The very small comparator arm makes that count especially imprecise as a basis for comparison. No confidence interval, test result, adjusted estimate, or time-to-event result is reported in the registry record. The brief summary mentions incidence and time to respiratory failure and/or death during the first 72 hours and 28 days of life, but the posted primary outcome is specifically a count at 28 days of life.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either met the definition of respiratory failure due to RDS or death by 28 days of life, or did not. The registry reports the number meeting the definition and the number enrolled in each arm. This kind of outcome is often summarized using counts and proportions. The posted values are counts: 6 of 11 in the lucinactant-plus-nCPAP arm and 0 of 1 in the nCPAP-only arm. No proportions or comparative effect estimates are reported in the registry record, and no additional values should be inferred from those counts when describing the posted analysis.

What would a comparative estimate add?

General statistical explanation: a comparative estimate expresses how outcome frequency differs between study groups, using a chosen scale such as an absolute difference or a relative measure. A confidence interval describes the uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision; a wider interval indicates less precision. When an arm has very few participants, estimates can be highly uncertain and may be sensitive to individual outcomes. The registry record does not provide an estimate or confidence interval for this endpoint.

The registry record specifically notes that a two-arm comparison for the binary endpoint was not estimable from the posted values. That means the record does not support a reported formal comparison. It does not mean that the raw counts are unavailable: the counts are posted and can be described directly. It does mean that readers should not substitute an unreported statistical test, effect measure, or confidence interval for the analysis that is absent.

Why does the arm-size imbalance matter?

General statistical explanation: randomized studies aim to make treatment groups comparable through allocation, but the realized group sizes still affect the amount of information available. A larger group generally contributes more observations; a group with only one participant provides very little information about the range of possible outcomes. Here, the posted arm sizes are 11 and 1. The comparator result therefore cannot characterize outcome variability among a broader set of comparable participants. The registry record does not explain the imbalance, so its cause cannot be determined from the posted information.

The study summary states that half of participants would receive lucinactant and half would receive standard of care, but the recorded group sizes are not equal. The summary describes the planned distribution; the posted counts describe the observed enrollment. These are distinct pieces of information. The record does not report an allocation procedure beyond identifying the study as randomized, nor does it describe any adjustment for the observed imbalance.

What do the planning assumptions mean?

General statistical explanation: sample-size planning uses assumptions about the effect a future study is intended to detect, the significance level, allocation, and the statistical method. A planning calculation illustrates what sample size could be required under those assumptions; it does not show that a study had a particular probability of detecting an effect after the results are known. The record describes planning illustrations based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. These illustrations are not the trial’s own sample-size justification, which is not reported in the registry record.

Because the observed effect is based on a small study with one comparator participant, planning calculations derived from it would inherit substantial uncertainty. They should be interpreted as hypothetical illustrations, not as evidence that the trial was adequately powered, and not as observed power. The record does not report a prospective sample-size rationale or the assumptions used by the study team when designing the trial.

How should the event definition be handled?

The primary endpoint is a combined participant-level outcome. Respiratory failure due to RDS is defined as intubation for mechanical ventilation and/or surfactant administration, and death is also included. A participant meeting either part of the definition is counted as having the combined outcome. The record does not report the component counts separately, so the total count cannot be decomposed into respiratory failure events and deaths. Nor does the primary outcome count describe timing within the 28-day period.

General statistical explanation: a time-to-event analysis uses the timing of events and can account for different follow-up durations under specified methods. A simple count of participants with an event does not preserve those event times. Although the study summary mentions time to respiratory failure and/or death, the posted primary outcome is a count at 28 days of life, and no time-to-event analysis is reported.

The study also lists secondary outcomes for BPD, mortality, and common complications of prematurity. The registry record does not report their results or the statistical methods used for them. It does not report an adjustment strategy for multiple outcome comparisons, missing-data methods, interim analyses, or a detailed analysis plan. These omissions limit assessment of how analyses were intended to be conducted and how uncertainty across outcomes was to be interpreted.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Lucinactant (160 mg/kg) + nCPAP", "nCPAP Only")
n      <- c(11, 1)
events <- c(6, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Lucinactant (160 mg/kg) + nCPAP  11  6  54.5  23.4  83.3  28.0  78.7  27.7  78.9
ARM  nCPAP Only  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes: BPD, mortality, and common complications of prematurity. It reports four outcome measures overall. The record does not describe a procedure for controlling the chance of false-positive findings across multiple outcomes, such as a testing hierarchy or adjustment method. It also reports no inferential analyses, so there are no posted secondary-outcome test results to interpret.

Handling of missing outcome data is not reported in the registry record. The primary population is identified as Intent-to-Treat, but the record does not explain how participants with incomplete follow-up, unavailable outcome information, or protocol deviations would be handled. It does not report whether any participants had missing primary outcome data. The enrollment and outcome counts alone do not establish the missing-data process.

No interim analysis plan or stopping boundary is reported in the registry record. The reason the study was terminated is also not reported, and no conclusion should be drawn about whether termination followed a planned review or a particular safety or efficacy finding. The record does not report a detailed statistical analysis plan, adjustment covariates, or sensitivity analyses. These gaps prevent readers from evaluating the planned approach to multiplicity, missingness, and analysis populations beyond the primary population label.

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: duodenal atresia (9.1%), pneumonediastinum (9.1%), pneumothorax (9.1%).

The adverse-event summary reports serious adverse events affecting 2 of 11 participants in the lucinactant-plus-nCPAP arm and 0 of 1 participant in the nCPAP-only arm. It reports no deaths in either group. These are descriptive counts, and the comparator figure represents only one participant. No inferential safety comparison or confidence interval is reported in the registry record.

The listed serious adverse-event terms are Duodenal atresia, Pneumonediastinum, and Pneumothorax, each shown with 9.1%. The record does not make clear in this listing which treatment arm each term belongs to, nor does it provide enough detail to determine whether terms overlap within participants. The displayed percentages should therefore be read as posted, without assigning them to an arm or treating the terms as separate participants.

The summary also reports other adverse events affecting 11 of 11 participants in the lucinactant-plus-nCPAP arm and 1 of 1 participant in the nCPAP-only arm. Those figures describe whether participants were affected, not the number or severity of individual events. The registry record does not provide event-level detail or an inferential comparison. Given the enrollment size and the single-participant comparator, these counts offer limited information for comparing safety outcomes across groups.

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

The posted results establish what was recorded in this trial: among 11 participants assigned to lucinactant with nCPAP, 6 met the primary outcome definition of respiratory failure due to RDS or death by 28 days of life; among 1 participant assigned to nCPAP alone, 0 met that definition. The primary endpoint is a combined count, and the registry does not separate respiratory failure from death within that result.

Those observations do not establish the size or precision of a treatment effect. The registry record contains no confidence interval, p-value, or reported comparative estimate, and indicates that a two-arm comparison was not estimable from the posted values. With only one participant in the comparator arm, its observed outcome cannot provide a reliable picture of the range of outcomes that might occur among similar participants. A raw contrast between the counts is not itself proof of a causal difference.

The results also do not establish that the study was adequately powered. The registry record does not report the study’s sample-size justification, and any planning illustration based on the observed effect is hypothetical rather than an assessment of observed power. The record does not explain the termination, the unequal group sizes, or whether missing outcome information existed. Those uncertainties further constrain interpretation.

The record lists three secondary outcomes, but does not report their results or the analysis plan for them. It therefore does not support conclusions about those outcomes or about consistency across different measures. The safety summary is also descriptive, with very limited information in the comparator arm and no reported inferential safety analysis.

In short, the counts are observations from a small terminated randomized study, not a precise estimate of what would happen in a broader population. The registry record supports a careful description of those observations and their limitations; it does not support a definitive claim about efficacy, lack of efficacy, or comparative safety.

14. Why This Trial Matters Statistically

This trial illustrates how a randomized design and a small observed enrollment can coexist. Randomization is a study-design feature, but the posted groups contain 11 and 1 participant. The imbalance is central to statistical interpretation: the primary outcome count in the comparator group is based on a single observation, leaving very limited information for estimating the comparator outcome frequency or a treatment contrast.

It also demonstrates the difference between reporting an endpoint count and conducting an inferential comparison. The registry reports the numbers meeting the combined primary outcome definition, but no comparative estimate or uncertainty interval. The record notes that a two-arm comparison was not estimable. Without an inferential analysis, the counts should not be treated as a precise measure of the effect that might be expected in other participants.

The endpoint itself raises an important interpretive distinction. It combines respiratory failure due to RDS, defined through intubation and/or surfactant administration, with death. The total count captures participants meeting the composite definition but does not reveal which component occurred or when. Although the brief summary mentions time to an event, the posted primary result is a count at 28 days of life. This underscores why the exact outcome definition and the analysis actually reported matter.

The study’s termination and the difference between the planned half-and-half distribution in the summary and recorded arm sizes are also important context. Their explanations are not reported in the registry record. Statistical interpretation should distinguish what the record documents from what might be hypothesized about recruitment or study conduct.

Finally, hypothetical sample-size planning based on an observed effect is not a substitute for a prospective design rationale or for adequate information in the observed groups. This trial is a useful example of why uncertainty, endpoint definition, analysis availability, and enrollment patterns must be considered together when reading clinical trial results.

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.

The most immediate limitation is the small enrollment: 12 participants overall, with 11 in the lucinactant-plus-nCPAP arm and 1 in the nCPAP-only arm. The comparator count offers especially little information about outcome frequency or variability. The primary result of 0 events in that arm describes the one enrolled participant; it cannot, by itself, establish that events would be absent in a larger group.

The registry record reports 6 participants with the primary outcome in the lucinactant arm, but no confidence interval, hypothesis test, or comparative effect estimate. It states that a two-arm comparison was not estimable from the posted values. This prevents assessment of the precision of the contrast and leaves the result descriptive. The reason the planned half-and-half distribution differs from the recorded arm sizes is not reported.

The study status is terminated, but the reason for termination and the circumstances around it are not reported in the registry record. Consequently, the effect of termination on enrollment, follow-up, or interpretation cannot be determined. The record does not state whether missing primary outcome data occurred or how missing data would have been handled. It identifies the primary population as Intent-to-Treat but gives no further analysis-population details.

The primary outcome combines respiratory failure and death and does not provide component-specific counts. The brief summary mentions time to respiratory failure and/or death, but no time-to-event result is posted. Results for the three listed secondary outcomes are also not reported. The record does not provide an analysis plan, multiplicity strategy, interim-analysis information, or prospective sample-size justification. These limitations restrict both clinical interpretation and evaluation of the statistical methods.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Safety and Efficacy Study of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks Gestational Age — NCT04264156.
• Registry record last updated 2023-05-24; status last verified 2023-04.
• Results first posted 2023-05-24.
• 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.

19. Record Summary

The registry record describes NCT04264156, a Phase 2 randomized, parallel-group, triple-masked study of inhaled lucinactant with nCPAP versus nCPAP alone in preterm neonates 26 to 32 weeks gestational age with RDS. The study started on 2020-04-18, had a primary completion date of 2021-01-31, enrolled 12 participants, and is listed as terminated.

The primary outcome is the number of participants with respiratory failure due to RDS or death by 28 days of life. The posted count is 6 of 11 participants in the lucinactant-plus-nCPAP arm and 0 of 1 in the nCPAP-only arm. The registry record does not report an inferential comparison and indicates that a two-arm comparison was not estimable from the posted values.

Three secondary outcomes are listed, but their results are not reported. The reason for termination, missing-data handling, detailed analysis plan, and sample-size justification are not reported in the registry record. The small enrollment and single-participant comparator arm make the primary counts descriptive and limit conclusions about comparative effects.