A Study of Inhaled Ampion in Adults With Respiratory Distress Due to COVID-19: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Inhaled Ampion in Adults With Respiratory Distress Due to COVID-19 (NCT04868890), a randomized phase 2 study. The primary outcome is Clinical Improvement of Participants of Ampion Compared to Placebo.

2. Clinical Question

The clinical question is therefore about whether the pattern of ordinal clinical status differed between Ampion and placebo over the stated follow-up, and how precisely that difference was estimated. The record supplies the outcome definition but no group means, change estimates, confidence intervals, or primary-outcome test result. The registry lists a secondary outcome concerning treatment-emergent adverse events, but those safety counts do not substitute for an efficacy comparison.

3. Trial Design

The study, NCT04868890, is titled “A Study of Inhaled Ampion in Adults With Respiratory Distress Due to COVID-19.” Its official title describes a randomized, double-blinded, placebo-controlled Phase II study. The registry lists quadruple masking and a parallel model. The active arm is Ampion and the control arm is placebo.

The registry lists enrollment as 200. That is the registered enrollment figure; the record does not establish from this information how many participants were ultimately randomized, treated, or included in each outcome analysis. The study start date is 2021-06-22 and the primary completion date is 2022-02-16. Its status is terminated. The reason for termination is not reported in the registry record, so the status alone cannot explain why the study ended or how it affected the conduct of the trial.

The primary outcome is described for the ITT population and concerns change in a mean score on the WHO 8 point ordinal scale. The timeframe field identifies Day 28, while the outcome description refers to change from baseline through Day 5 and through Day 28. The registry record does not explain how those assessment points were combined, which point was designated for a single primary comparison, or how repeated measurements were handled in the analysis.

A secondary outcome is the number of participants with treatment-emergent adverse events of Ampion compared with placebo. The record includes adverse-event counts by group, but it does not report an efficacy analysis for the primary endpoint. It lists two outcome measures and zero analyses. The statistical analysis plan, including the intended model, adjustment variables, handling of missing observations, and any interim-analysis procedures, is not reported in the registry record.

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: Intent to Treat (ITT)

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 Clinical Improvement of Participants of Ampion Compared to Placebo, measured over Day 28.

The primary endpoint is clinical improvement assessed with a score on the WHO 8 point ordinal scale. The scale ranges from no clinical or virological evidence of infection to death, with intermediate categories describing limitations in activity, hospitalization without oxygen, levels of oxygen or respiratory support, and additional organ support. It records the highest level of support required on the day being recorded.

The outcome description concerns change from baseline through Day 5 and through Day 28. Its parameter is the mean, and its dispersion measure is the standard deviation. The description states that a negative difference in mean score constitutes a reduction in the severity of clinical intervention. This direction matters when interpreting a comparison: a lower score represents a less severe category of clinical support under the scale’s definitions.

Ordinal scales can summarize clinically different states in an ordered form. They are used when outcomes progress through categories rather than being measured on a single physical scale. However, a mean change summarizes the scores numerically and does not show how many participants occupied each category or moved between categories. Those details can matter for understanding the distribution of patient status.

The registry record does not report the group means, mean changes, between-group estimate, uncertainty interval, or test result for this endpoint. It also does not clarify the analysis of the Day 5 and Day 28 assessments. The endpoint definition explains what was intended to be measured, but it does not by itself reveal the observed clinical-improvement result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, parallel, placebo-controlled Phase II study with quadruple masking. These design features describe how the study was organized, not the statistical results. Random assignment is generally used to reduce systematic differences between groups at entry. Masking is generally intended to limit the influence of treatment knowledge on participant experience, clinical management, outcome assessment, or analysis, depending on who is masked. The registry does not identify the specific people covered by its masking designation or describe how masking was maintained.

What does a mean on an ordinal scale represent?

The primary outcome uses a mean score and standard deviation for a clinical scale with ordered categories. In general, an ordinal scale ranks states from less severe to more severe without necessarily implying that the distance between adjacent categories is identical. A mean can provide a compact summary of group scores, while the standard deviation describes how spread out the scores are around that mean. Neither summary alone shows the full distribution across categories. For this endpoint, the registry describes a negative difference in mean score as a reduction in severity of clinical intervention.

Change from baseline compares a participant’s follow-up score with that participant’s starting score. A group-level mean change can then summarize those participant-level changes. A between-group estimate compares the summaries for Ampion and placebo. In general, the interpretation depends on how the change was defined, which participants contributed measurements, and whether the analysis adjusted for baseline score or other factors. Those analysis details are not reported in the registry record.

Why does the assessment time matter?

The outcome description refers to change through Day 5 and through Day 28; the timeframe field identifies Day 28. Multiple assessments can describe how an outcome develops over time, but they also require a clear analysis rule. An analysis might treat each time point as a separate comparison or model repeated measurements together; these are general possibilities, not claims about this trial. The registry does not state which approach was used or identify a single primary time-point comparison.

What does uncertainty mean?

In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while the interval’s location describes which effects remain compatible with the data and method. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it does not measure clinical importance. The registry record reports no primary effect estimate, confidence interval, or p-value, so these features cannot be evaluated for this outcome.

What can the adverse-event counts show?

Safety counts are descriptive summaries of events or participants affected, as recorded. Comparing counts across groups can be useful, but interpretation also depends on definitions, observation periods, completeness of reporting, and whether the values refer to events or participants. Serious adverse events and other adverse events are distinct summaries in this record. General statistical caution is warranted when interpreting selected event terms, especially when no inferential analysis or context for their selection is reported. The record does not provide a statistical comparison for these safety data.

How should planning illustrations be read?

General sample-size calculations describe the amount of information a hypothetical study might require under stated assumptions. The registry describes planning illustrations based on the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation; the target effect is stated as a fraction of the observed effect. The illustrations are not the trial’s observed power and are not evidence that the study had a particular probability of detecting an effect. No numerical illustration values are stated in the registry information summarized for this analysis. The registry record also does not report the trial’s own sample-size justification or design assumptions.

For non-time-to-event outcomes, the planning description refers to participants per arm; time-to-event illustrations refer to total events. These are planning conventions, not outcome results. A planning calculation cannot fill the gap left by an unreported primary analysis. It should be interpreted as a hypothetical design aid rather than as a substitute for the estimated treatment effect and its uncertainty.

Overall, the record provides design labels and endpoint definitions but not the analysis specifications needed to reproduce or fully interpret the primary comparison. The statistical model, treatment of repeated assessments, missing-data method, covariate adjustment, multiplicity approach, and analysis diagnostics are not reported in the registry record. Any explanation of those methods would therefore be general rather than a description of procedures known to have been used in this study.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description includes change from baseline through Day 5 and through Day 28. Considering more than one assessment can raise a multiplicity question: when multiple comparisons are used to support a conclusion, the chance of a false-positive finding may increase unless the analysis plan addresses that issue. This is a general statistical concern, not evidence that a particular adjustment was required or omitted in this trial. The registry record does not report whether the time points were analyzed separately, whether one was designated as primary for inference, or whether any multiplicity adjustment was used.

The record lists two outcome measures and zero analyses. It names the primary outcome population as Intent to Treat (ITT), but does not describe the analysis set in detail or state how participants with missing measurements were handled. Missing data can affect estimates when the availability of an outcome is related to participant status or treatment experience. Common approaches rely on assumptions about why observations are missing; without the analysis plan and outcome-level data, those assumptions cannot be assessed. The number of missing primary-outcome observations is not reported in the registry record.

The statistical analysis plan, including any prespecified hierarchy of endpoints, is not reported in the registry record. It is therefore not possible to determine how the primary and secondary outcomes were intended to contribute to inference, or whether analyses were adjusted for multiple outcomes, time points, or interim looks. No interim-analysis procedure is reported. These omissions limit assessment of how the endpoint and analysis decisions were prespecified, but they do not establish that any particular method was or was not used outside the information in the registry.

11. 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: acute respiratory distress syndrome (3.1%), chest pain (1.5%), sepsis (1.5%), pulmonary embolism (1.5%).

The registry lists serious adverse-event figures by group. For Active, 64 participants were at risk and 2 were affected; for Control, 65 were at risk and 4 were affected. The registry also lists other adverse-event figures: 21 of 64 at risk in Active and 18 of 65 at risk in Control. These are descriptive entries as recorded; the registry information does not provide a statistical comparison for them.

The listed deaths are 2 for Active and 1 for Control. These counts do not establish that treatment caused or prevented a death, and the record does not provide the circumstances needed to interpret them further. Serious-event terms listed among the leading entries are Acute Respiratory Distress Syndrome at 3.1%, Chest Pain at 1.5%, Sepsis at 1.5%, and Pulmonary Embolism at 1.5%. The registry information does not specify the denominator or selection method for these percentages, so they should be read as reported rather than assigned an assumed interpretation.

Event counts can be affected by duration of observation, event definitions, and completeness of reporting. The record does not provide enough detail to assess those aspects or to infer a causal relationship. Safety summaries should be considered separately from the unreported primary efficacy analysis.

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

The registry record describes a randomized, quadruple-masked, placebo-controlled Phase II study of inhaled Ampion in adults with respiratory distress due to COVID-19. It identifies a clinical-improvement outcome based on change in an ordinal score and reports selected adverse-event information. It also marks the study as terminated.

What the record does not provide is a numerical result for the primary comparison. There is no reported group mean, change estimate, confidence interval, or test result for the clinical-improvement endpoint. Accordingly, the posted information does not show whether the primary outcome favored Ampion or placebo, how large any difference was, or how precisely it was estimated. The endpoint definition alone cannot answer those questions.

The safety counts provide descriptive information about adverse events as recorded, not a standalone causal assessment. They do not establish that Ampion caused or prevented an event. Similarly, the terminated status is a description of study status, not an explanation of why the study ended and not an efficacy finding.

General statistical interpretation requires attention to the scale, assessment times, analysis population, missing observations, and uncertainty around estimates. The registry record does not report enough analysis detail to resolve these issues for the primary outcome. This means that the available record can support a description of the intended question and the safety entries, but not a conclusion about the comparative clinical-improvement effect.

These limits concern what is reported in the registry record. They should not be replaced with assumptions about unreported results, the reasons for termination, or the methods the investigators may have used. A treatment conclusion would require appropriately reported outcome estimates and their uncertainty, together with sufficient methods and context to interpret them.

13. Why This Trial Matters Statistically

This trial raises several statistical issues that are common in studies of clinical status. The primary outcome uses an ordinal scale whose categories represent ordered levels of clinical condition and support. Summarizing such scores with a mean can be concise, but it may conceal how participants are distributed across categories or whether changes occur in particular parts of the scale. Interpretation benefits from seeing both a clearly defined estimand and enough outcome detail to understand what the summary captures.

The endpoint description also refers to change through Day 5 and through Day 28. When outcomes are assessed repeatedly, the analysis must make clear whether the focus is a particular visit, change over time, or another summary. Prespecification and transparent reporting matter because multiple possible comparisons can complicate interpretation. The registry record does not describe the analysis approach for these assessments.

Randomization and masking are important design features, but they do not replace outcome reporting. A reader still needs an effect estimate and a measure of uncertainty to judge what the study observed. Here, the record lists the design and outcome definition but no numerical primary analysis. This illustrates why a trial’s status and design alone cannot answer its clinical comparison question.

The safety information also illustrates the distinction between descriptive counts and causal inference. Counts and selected percentages can identify what the registry reports, but interpretation depends on definitions, exposure and follow-up context, and the method used to compare groups. The primary efficacy result and analysis details are not reported in the registry record, so the available information is limited to the study description and posted safety entries.

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 main limitation of the registry record for interpreting efficacy is that it contains no numerical result for the primary outcome. The record lists zero analyses, and it does not provide group summaries, a between-group estimate, a confidence interval, or a test result. Without these, the direction, magnitude, and precision of the clinical-improvement comparison cannot be evaluated.

The timing and analysis of the endpoint are not fully specified in the reported information. The outcome description refers to change from baseline through Day 5 and through Day 28, while the timeframe field identifies Day 28. The record does not state how these assessments were combined or which comparison was used for inference. It also does not describe the statistical model, adjustment variables, or assumptions used for the ordinal score.

The record names the ITT population but does not report the number analyzed or the handling of missing outcome data. It does not provide baseline characteristics or detail the numbers randomized, treated, and followed for each outcome. The reason for termination is not reported in the registry record, so the effect of termination on enrollment, follow-up, or analysis cannot be determined from this information.

For safety, the posted counts and selected event-term percentages are not accompanied by a statistical comparison or enough context to determine the denominator and selection method for each percentage. The record also does not give the event definitions or observation details needed for a fuller comparison. These reporting limitations constrain interpretation; they do not establish that unreported methods or results do not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Inhaled Ampion in Adults With Respiratory Distress Due to COVID-19 — NCT04868890.
• Registry record last updated 2022-12-07; status last verified 2022-05.
• Results first posted 2022-12-07.
• 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

NCT04868890 is a randomized, quadruple-masked, parallel Phase II study of inhaled Ampion versus placebo in adults with respiratory distress due to COVID-19. The registry lists enrollment as 200, a start date of 2021-06-22, a primary completion date of 2022-02-16, and status as terminated.

The primary outcome is clinical improvement, measured as change in a mean score on the WHO 8 point ordinal scale from baseline through Day 5 and through Day 28, with the ITT population named. The registry record lists two outcome measures and zero analyses, and does not report a numerical primary-outcome result. It includes descriptive adverse-event counts and selected serious-event terms. The reason for termination, statistical analysis plan, and missing-data procedures are not reported in the registry record.