VentaProst in Subjects With COVID-19 Requiring Mechanical Ventilation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for VentaProst in Subjects With COVID-19 Requiring Mechanical Ventilation (NCT04452669), a randomized phase 2 study. The primary outcome is Change in Respiratory Failure.

2. Clinical Question

In statistical terms, the question is whether the observed extubation counts differ between the randomized arms at the stated assessment time. Extubation is a clinically relevant milestone for respiratory support, but the endpoint as posted is a count at a particular time rather than a time-to-extubation analysis. The record does not report how participants who were not extubated by that time were classified beyond the stated count outcome, nor does it provide information about events such as death before extubation or other competing outcomes. Those details matter when interpreting a binary status outcome in a critically ill population.

The trial was phase 2, randomized, quadruple-masked, and parallel-group. These design features describe how the study was organized; they do not, by themselves, quantify the uncertainty in the result. The small enrollment and absence of a reported inferential analysis are central to reading the available evidence: the posted outcome is descriptive, while the magnitude and precision of any between-arm effect are not reported in the registry record.

3. Trial Design

This was a phase 2, randomized, quadruple-masked, parallel-group study with a placebo control. The trial title identifies VentaProst in subjects with COVID-19 requiring mechanical ventilation, and the official title describes inhaled epoprostenol delivered via a dedicated delivery system. The sponsor was Aerogen Pharma Limited. The registry record gives the study status as completed, enrollment as 11, a start date of 2020-09-15, and primary completion on 2021-06-29.

Participants assigned to the Study Treatment arm received inhaled epoprostenol through a breath-actuated dedicated delivery system for up to 10 days. Participants assigned to the Placebo Control arm received inhaled 0.9% sodium chloride solution through the same described type of system for up to 10 days. The registry record identifies the intervention as a drug and the condition as COVID-19. It does not give further details about dosing, treatment adherence, concomitant care, or the exact procedures used to maintain masking.

The primary outcome was titled “Change in Respiratory Failure.” Its operational description is the number of participants that were extubated, with assessment at 10 days post-randomization in the ITT Population. The posted arm counts are 3 of 6 for Study Treatment and 2 of 5 for Placebo Control. These are descriptive outcome counts; a statistical comparison is not reported.

The record lists 2 outcome measures, but no secondary outcomes are posted in the information used for this analysis. It also reports 0 analyses. The registry record does not report the planned statistical model, treatment-effect measure, confidence-interval method, or hypothesis-testing procedure. Nor does it report a sample-size justification or interim-analysis plan. The randomized design can reduce confounding on average, but the record’s small enrollment and lack of a posted analysis limit what can be concluded from the observed arm counts.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population

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 Change in Respiratory Failure, measured over 10 days post-randomization.

The primary endpoint is the number of participants who were extubated 10 days post-randomization. The registry describes the endpoint under “Change in Respiratory Failure,” specifies participants as the unit, and identifies the ITT Population. The posted result is 3 of 6 in Study Treatment and 2 of 5 in Placebo Control.

Extubation indicates that a participant has been taken off mechanical ventilation by the assessment time. As a binary outcome, it records whether each participant met the endpoint at that time, rather than how long extubation took or the degree of respiratory improvement. This can make the outcome straightforward to describe, but it compresses a clinical course into a status at a defined time. Participants extubated earlier and participants extubated near the assessment time are counted alike in this endpoint.

The fixed assessment time also means the result should be understood specifically as extubation status 10 days post-randomization. It is not, on its own, a measure of later respiratory status, duration of ventilation, or survival. The registry record does not report a time-to-event analysis, additional details about how deaths or other events before assessment were handled, or a broader composite definition. The outcome therefore addresses a focused milestone, while leaving those other dimensions uncharacterized in the posted endpoint result.

For a binary endpoint, the counts are most informative when accompanied by an effect estimate and an interval describing its uncertainty. Neither is reported in the registry record. With only the arm counts available, the direction and precision of a comparative effect cannot be established from a formal analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. The primary endpoint is binary: a participant is counted as extubated or not extubated at the specified assessment. The record reports arm-level counts and denominators, but lists no analyses. It also indicates that values were missing or not estimable for a two-arm comparison. Accordingly, there is no posted inferential result to interpret for the primary endpoint.

What does a binary outcome comparison estimate?

General statistical explanation: a binary endpoint can be summarized within each arm as the proportion meeting the endpoint, and the arms can be compared using an effect measure such as a risk difference, risk ratio, or odds ratio. Each measure expresses a different form of comparison and has its own interpretation. The registry record does not report which effect measure, if any, was planned for this trial. No new effect estimate is calculated in this interpretation.

The distinction between a group count and an estimated treatment effect is important. Counts describe the observed participants. An effect estimate attempts to quantify how outcomes compare between assigned groups, while an uncertainty interval communicates how imprecisely that comparison has been estimated. A formal test may also assess compatibility with a specified null hypothesis, but a p-value alone would not communicate the size or clinical meaning of an effect. None of these comparative statistics is reported for the primary outcome.

Why does the absence of an interval matter?

General statistical explanation: a confidence interval is a range of values generated by a method designed to have a stated long-run coverage property under its assumptions. It helps readers distinguish a relatively precise estimate from one that remains compatible with a broad range of effects. For binary data, intervals can be especially wide when information is limited, and their behavior depends on the estimation method. Since the registry record does not report an interval, the precision of the primary comparison cannot be assessed from the posted counts alone.

Small studies can produce unstable-looking group summaries because individual outcomes make up a larger part of the available information. That does not mean the observed counts are invalid; it means they should not be treated as precise evidence about the treatment effect without suitable uncertainty estimates. The record’s enrollment is 11, and the arm-specific primary outcome counts are 3 of 6 and 2 of 5. No inferential analysis accompanies them.

What is the role of randomization?

General statistical explanation: random assignment is intended to prevent systematic allocation of participants according to prognosis or other characteristics. If conducted and maintained appropriately, it supports causal comparisons between assigned groups. Randomization does not ensure that measured or unmeasured characteristics will be balanced in every realized trial, especially when enrollment is limited. Baseline characteristics and details of the randomization procedure are not reported in the registry information used here, so neither balance nor implementation can be independently described.

The study is identified as randomized, quadruple-masked, and parallel-group. These labels describe design features, but they do not substitute for a prespecified analysis or a clear account of outcome handling. The registry record does not report the masking procedures, allocation ratio, or statistical model. It therefore is not possible to say whether the primary analysis was adjusted, which test was planned, or how missing outcome information would be addressed.

How should the planning illustrations be understood?

The record describes sample-size assumptions as a planning illustration based on the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. Those assumptions describe an illustrative calculation, not the design justification for this study. The registry record does not report the trial’s own sample-size justification.

General statistical explanation: a sample-size calculation asks how much information a hypothetical study would require under chosen assumptions and a target power. It is not a measure of the power actually achieved by a completed study. Any planning illustration based on an observed effect is particularly dependent on that effect estimate, which may be imprecise. Such figures should therefore be treated as hypothetical planning aids, not as evidence that the completed trial had a particular probability of detecting an effect.

The stated planning description refers to participants per arm for non-time-to-event calculations and to total events for time-to-event calculations. The primary endpoint in this record is a binary participant count, rather than a time-to-event endpoint. No numerical planning results are described in the registry information used for this analysis, and none should be inferred from the assumptions alone.

What does “not estimable” convey?

The registry record’s note that values were missing or not estimable for a two-arm comparison signals that the relevant comparative values were not available in the posted results. It does not identify a reason, such as a specific model failure or a prespecified threshold, so no such explanation can be attributed to the trial. The record lists 0 analyses. In practical terms, readers can describe the arm-level counts but cannot cite a registry-reported formal comparison of those counts.

General statistical explanation: when an analysis is not available, reconstructing one from summary counts may not match the trial’s planned method, analysis population, or handling of outcomes. Alternative methods can also yield different intervals or tests, particularly with limited data. For this reason, an unadjusted reconstruction would not replace a sponsor-reported analysis. The registry record reports no such analysis, and the posted descriptive counts should remain clearly distinguished from inferential conclusions.

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("Study Treatment", "Placebo Control")
n      <- c(6, 5)
events <- c(3, 2)
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  Study Treatment  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Placebo Control  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures, but no secondary outcomes are posted in the information used for this analysis. It reports 0 analyses. A multiplicity strategy, such as a testing hierarchy or adjustment across outcomes, is not reported in the registry record. Without a reported analysis plan, it is not possible to determine whether the primary endpoint was the only formally tested outcome, whether multiple comparisons were planned, or how any multiplicity was addressed.

The primary endpoint is stated for the ITT Population. This identifies the population label attached to the endpoint, but the registry record does not give a detailed definition of that population or say how participants were handled in the analysis. In particular, it does not report missing outcome counts, reasons for missingness, imputation methods, sensitivity analyses, or rules for handling intercurrent events such as death before the assessment. The absence of these details should not be interpreted as evidence that there were no missing observations or no such events.

General statistical explanation: missing-data methods rely on assumptions about why information is unavailable. Different assumptions can produce different estimates, and sensitivity analyses can help show how conclusions depend on those assumptions. For a binary outcome measured at a fixed time, it is also important to know how outcomes that prevent or complicate assessment are classified. Those procedures are not reported in the registry record.

The registry record indicates that values were missing or not estimable for a two-arm comparison of the binary endpoint. It does not explain whether this reflects missing participant outcomes, an unavailable statistical output, or another issue. Therefore, it cannot support a more specific account of missingness or analysis-population handling. The posted arm counts remain descriptive, and no multiplicity-adjusted or missing-data-adjusted comparative result is available.

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: worsening of acute hypoxic respiratory failure (60.0%), worsening of ards (20.0%), hypercapnic respiratory failure (20.0%).

The posted serious adverse event figures are 1 affected participant among 6 at risk in the Study Treatment arm and 4 among 5 at risk in the Placebo Control arm. For other adverse events, the counts are 0 among 6 at risk in the Study Treatment arm and 1 among 5 at risk in the Placebo Control arm. The registry also reports 1 death in the Study Treatment arm and 4 in the Placebo Control arm.

These figures are descriptive counts, not estimates of a causal treatment effect. The registry record does not report a formal statistical comparison, confidence intervals, or details that would establish whether events overlapped within participants or how adverse events were classified and collected. The counts should not be added across categories or interpreted as distinct participants across all outcomes.

The record lists the leading serious adverse event terms as Worsening of Acute Hypoxic Respiratory Failure (60.0%), Worsening of ARDS (20.0%), and Hypercapnic Respiratory Failure (20.0%). The denominator and method used for these percentages are not reported in the registry record. The terms describe the posted safety information, but the figures alone do not show whether an event was caused by the study treatment or the underlying illness.

Small group counts can be highly sensitive to individual outcomes. The safety summaries therefore warrant descriptive interpretation only, without conclusions about comparative risk or safety.

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

The posted primary outcome result is that 3 of 6 participants in the Study Treatment arm and 2 of 5 in the Placebo Control arm were extubated 10 days post-randomization. This tells readers what was recorded in each randomized group for the stated endpoint and assessment time. It does not establish a reliable difference between the assigned treatments, because the registry record does not provide a comparative estimate or its uncertainty.

The study’s randomized, quadruple-masked, parallel-group design is relevant context for interpreting a comparison. However, design labels cannot resolve the absence of a reported analysis. The registry record does not report a treatment-effect estimate, confidence interval, p-value, analysis model, or details of outcome handling. The posted counts therefore should not be presented as proof that either treatment is superior, equivalent, or ineffective.

The endpoint also has a limited scope. It records extubation status at 10 days post-randomization, not time to extubation, duration of mechanical ventilation, later respiratory status, or a complete measure of clinical course. The record does not describe how deaths or other events before the assessment were incorporated into the endpoint. These gaps constrain what the primary result can say about outcomes beyond the stated milestone.

The safety counts provide a separate descriptive account of serious adverse events, other adverse events, and deaths in the two arms. They do not establish causation or a comparative safety effect. The registry record does not give uncertainty estimates or the detail needed to assess the relationship between adverse events and treatment assignment.

In general, a trial’s observed results are evidence about the participants and outcomes recorded, while broader conclusions depend on precision, design, outcome definitions, and analysis. Here, the small enrollment and absence of reported inferential results make precision particularly difficult to evaluate. The registry record does not establish how results would generalize to other patients or settings. The most defensible conclusion is limited to describing the posted outcome and safety counts, while recognizing that their comparative meaning is unresolved.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a randomized design and a reported estimate that readers can evaluate. Randomization is an important foundation for comparing assigned groups, but the registry record’s primary outcome is presented as arm-level counts without a treatment-effect estimate, confidence interval, or statistical test. As a result, the direction and precision of the comparative effect are not quantified in the posted results.

The endpoint is a binary clinical milestone at a defined time: extubation 10 days post-randomization. That definition makes the result readily interpretable as a status at the assessment, while also emphasizing what it does not capture. It does not report the timing of extubation, duration of ventilation, or later clinical course. A precise endpoint definition and clear handling of events before assessment are essential when evaluating such outcomes; those handling details are not reported in the registry record.

The trial also demonstrates why safety counts require context. Serious adverse events and deaths are posted by arm, but the record does not provide a formal comparison or uncertainty estimates. Counts alone cannot distinguish treatment effects from chance variation, underlying illness, or other factors. This is particularly important where the study enrollment is 11 and each observed outcome contributes materially to the group summaries.

Finally, the record shows why missing statistical reporting limits interpretation even when basic results are available. The registry indicates that comparative values were missing or not estimable and lists no analyses. Without the planned method, analysis population details, or missing-data procedures, readers cannot evaluate whether the posted result corresponds to a prespecified inferential approach. The statistical lesson is not that the observed counts are uninformative, but that descriptive results and evidence about a treatment effect are different kinds of information.

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 registry record contains limited information for evaluating the primary comparison. It reports the extubation counts by arm but no effect estimate, confidence interval, or p-value. It also states that values were missing or not estimable for a two-arm binary comparison and lists 0 analyses. The reason those comparative values are unavailable is not reported in the registry record.

Enrollment was 11, and the posted arm counts are small. This limits the amount of information available for interpreting the observed group results and makes precision difficult to judge without an interval estimate. The registry record does not report a sample-size justification or the trial’s statistical plan, so it is not possible to assess whether the study was designed around a specified treatment effect or inferential objective.

The primary endpoint is described as the number of participants extubated 10 days post-randomization in the ITT Population. The registry record does not give a fuller definition of that population, missing outcome information, or rules for classifying death or other events before assessment. It also does not report baseline characteristics or an adjusted analysis. These omissions limit assessment of comparability, outcome handling, and robustness.

The safety information is also descriptive. The record does not report event-collection methods, attribution procedures, overlap between categories, or inferential comparisons. The denominator for the percentages attached to the listed serious adverse event terms is not reported in the registry record. These limitations prevent a detailed comparative assessment of safety from the posted counts alone.

The study is phase 2 and addresses participants with COVID-19 requiring mechanical ventilation. Further details on eligibility, treatment exposure, co-interventions, and participant characteristics are not reported in the registry information used. The extent to which the results apply beyond the enrolled trial population cannot be assessed from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: VentaProst in Subjects With COVID-19 Requiring Mechanical Ventilation — NCT04452669.
• Registry record last updated 2025-07-31; status last verified 2025-07.
• Results first posted 2025-07-31.
• 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 a completed phase 2, randomized, quadruple-masked, parallel-group study sponsored by Aerogen Pharma Limited. It enrolled 11 participants, with a start date of 2020-09-15 and primary completion on 2021-06-29. The study compared inhaled epoprostenol delivered through a breath-actuated dedicated delivery system with inhaled 0.9% sodium chloride solution delivered through the same described type of system, for up to 10 days.

The primary endpoint was the number of participants extubated 10 days post-randomization in the ITT Population. The posted counts were 3 of 6 for Study Treatment and 2 of 5 for Placebo Control. The registry record reports no analyses and no comparative estimate or uncertainty interval for this binary outcome. Safety counts are posted by arm, but no formal safety comparison is reported. These results are descriptive, and the registry record does not establish a precise comparative treatment effect.