Efficacy and Safety of Polyoxidonium, Nasal and Sublingual Spray, 6 mg/ml in Children Aged 1-12 Years With ARI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Polyoxidonium, Nasal and Sublingual Spray, 6 mg/ml in Children Aged 1-12 Years With ARI (NCT03840135), a randomized phase 3 study. The primary outcome is Fever Duration (With a Superiority Cut-off Level δ=-0,52 Days).

2. Clinical Question

The central comparison is the mean duration of fever in the two assigned groups. The registry defines the end of fever as normalization of axillary body temperature to ≤ 36,9 °C, confirmed by two consecutive measurements. The outcome therefore depends on both the temperature threshold and confirmation across consecutive measurements, rather than on a single reading alone.

The trial record describes a prospective, randomized, double-blind, placebo-controlled, parallel-group phase 3 study conducted at multiple centers. It also lists secondary measures covering symptoms, treatment assessments, antifebrile-agent use, and discontinuation due to a requirement for antibacterial therapy. Those measures can add context to the primary comparison, but they do not replace the primary fever-duration question.

3. Trial Design

The registry describes a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group phase 3 study. It is marked completed, with enrollment of 172. The listed sponsor is NPO Petrovax. The registry dates are 2018-11-07 for study start and 2019-02-26 for primary completion.

Participants were assigned to Polyoxidonium 6 mg/ml or placebo. The Polyoxidonium regimen is described as nasal and sublingual spray at 0,15 mg/kg daily for 7 days. The placebo was also a nasal and sublingual spray, given for 7 days. The record specifies triple masking, but it does not identify which groups of people were masked.

The primary endpoint is mean fever duration, assessed at Day 8±1. The primary outcome summaries list 76 participants in the Polyoxidonium group and 79 in the placebo group. These are the denominators in the posted summaries; the registry record does not report why they differ from the total enrollment or provide a complete account of participant flow in the information available for this analysis.

The registry lists 11 secondary outcome measures, while results are posted for 10 secondary measures. They cover symptom scores and symptom categories at specified treatment days, investigator and parent/adopter assessments, antifebrile-agent use, and discontinuation because antibacterial therapy was required. The listed measures broaden the set of questions explored, but details of any prespecified ranking among secondary outcomes are not reported in the registry record.

Randomization and a placebo comparator support a structured between-group comparison. The registry record does not report the randomization procedure, allocation concealment details, or the roles included in triple masking. Those details should not be inferred from the design labels alone.

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:

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: 172 patients were randomized, 8 people dropped out during the trial (due to protocol violations and withdrawal of informed consent). 164 patients completed the study, data from 155 children were accepted for the final analysis (9 patients were excluded from the analysis due to protocol violations).

6. Primary Endpoint

The registry lists the primary outcome as Fever Duration (With a Superiority Cut-off Level δ=-0,52 Days), measured over Day 8±1.

The primary outcome is fever duration, reported as a mean in days. The registry sets the assessment timeframe at Day 8±1 and defines fever as ending when axillary body temperature is normalized to ≤ 36,9 °C, confirmed by two consecutive measurements. Thus, the endpoint is a duration measure based on a stated temperature rule, not simply whether a participant had a normal temperature at one visit.

A continuous measure such as duration can retain information about how long an event lasts across participants. Reporting a group mean gives a summary of those durations, while the confidence interval communicates uncertainty around that summary. The group means are 2.04 days for Polyoxidonium and 2.26 days for placebo. The registry reports a mean difference of -0.22 days for the final values.

The title of the primary outcome includes a superiority cut-off level of δ=-0,52 days. This is important to distinguish from a general question about whether the group means differ: a superiority question with a stated cut-off asks whether the between-group result meets that specified threshold. The registry record does not explain the rationale for selecting the cut-off or provide further detail on how the criterion was operationalized. The primary result therefore needs to be read alongside both the reported estimate and its uncertainty, rather than from the label “superiority” alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean difference describe?

For a continuous outcome, a mean difference compares the average value in one group with the average value in another. Here, the reported parameter is the mean difference in final values, and the registry reports -0.22 days for Polyoxidonium compared with placebo. The sign depends on the order of groups in the comparison; the registry lists Polyoxidonium first and placebo second. In general, a mean difference describes the separation between group averages, not the range of individual participants’ outcomes or the proportion of participants with a particular result.

What does the confidence interval add?

A confidence interval is a range of values compatible with the data and the method used to calculate it. In general, a 95% confidence interval describes the uncertainty around an estimate under repeated use of the same statistical procedure. It is not a guarantee that the true effect lies in the particular interval, and it does not show how outcomes varied from person to person. The primary interval is -0.6 to 0.16 days. Since it includes zero, it includes no mean difference as one value compatible with the interval. It also includes values in both directions.

The registry’s p-value statement should be read with that interval, not independently of it. A p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The reported two-sided test gives p <0.05, while the confidence interval includes zero. The record does not explain why these two summaries differ. This is a reporting inconsistency that limits interpretation.

Why does the superiority cut-off matter?

A superiority analysis can ask whether a treatment-group result is better by a specified amount, rather than merely whether the groups differ. The primary outcome title states δ=-0,52 days. The reported estimate is -0.22 days, and the interval runs from -0.6 to 0.16. The point estimate is not beyond the stated cut-off, and the interval includes values that do and do not cross it. The registry record does not report the justification for the cut-off or further decision rules, so those details should not be assumed.

What does a t-test contribute?

The primary reported method is a two-sided t-test. In general, a t-test compares means while accounting for the variability and sample size used in the test. “Two-sided” means that departures in either direction are considered. The registry does not post the standard deviations or other dispersion summaries for the primary groups, nor does it provide enough detail to reproduce the test independently from the group summaries alone. It also does not report whether any adjusted model was used alongside the stated test.

How should the secondary calculations be read?

The posted unadjusted secondary calculations compare binary outcomes using measures such as risk difference, risk ratio, odds ratio, confidence intervals, and p-values. In general, a risk difference expresses the separation between two group proportions; a risk ratio compares those proportions as a ratio; and an odds ratio compares the corresponding odds. These are different summaries and need not have the same numerical scale. A confidence interval that includes the no-difference value indicates uncertainty that includes no group separation under that measure. The secondary calculations are unadjusted comparisons, not replacements for the registry’s reported tests.

The registry lists Fisher Exact and Chi-squared methods for selected secondary comparisons. In general, these methods assess association between group assignment and a categorical outcome, with different calculation approaches. The registry does not provide a statistical analysis plan explaining when each method was selected. Some posted registry p-values for secondary analyses are stated as p <0.05, while the unadjusted calculations for those outcomes do not show the same degree of evidence. The record does not explain those differences.

What do the sample-size illustrations mean?

The planning illustrations are based on observed effects, with scenarios using 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. For these binary outcomes, the listed amounts are participants per arm for 80% power or participants per arm for 90% power. In general, a planning calculation estimates the sample size that would be needed under its assumptions to target a chosen power for a specified effect. These illustrations are not observed power, do not describe the trial’s original design justification, and should not be mistaken for the number enrolled or analyzed.

Why does over-dispersion matter in general?

Over-dispersion occurs when observed variation is greater than a statistical model assumes. In general, a model that underestimates variation can make uncertainty appear too small. The registry record does not report an over-dispersion assessment or a model-based analysis for the primary endpoint, so no conclusion about that issue can be drawn for this study.

10. Analyses Reported by the Sponsor

The registry’s primary reported analysis is a two-sided t-test of the final-value mean difference. It reports -0.22 days, a 95% confidence interval from -0.6 to 0.16, and p <0.05. The group summaries are 2.04 days for Polyoxidonium and 2.26 days for placebo. The point estimate favors a lower mean in the Polyoxidonium group, but the interval includes zero and the estimate does not reach the stated superiority cut-off of δ=-0,52 days.

The reported p-value and confidence interval do not tell a consistent story under the usual relationship between a two-sided test and its corresponding confidence interval. A p-value below 0.05 would ordinarily align with a 95% interval excluding the null value of zero; the posted interval includes zero. The registry record does not explain whether this reflects a difference in analysis details, reporting, or another issue. No resolution should be assumed from the posted information.

The record’s discrepancy flag is false, so there is no basis in that flag to designate the sponsor’s analysis as taking precedence over a recalculation. The posted primary summaries do not include enough dispersion detail to reproduce the t-test independently. Interpretation should therefore preserve the registry’s reported values while noting the inconsistency and the missing analysis details, rather than substituting an unverified explanation.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists multiple secondary outcomes. However, a multiplicity adjustment, testing hierarchy, or other approach for controlling the interpretation of multiple comparisons is not reported in the registry record. In general, when many outcomes are tested, unadjusted p-values do not account for the increased opportunity to observe apparently notable results by chance. The secondary p-values should therefore be understood as nominal unless the record provides evidence of an adjustment; no such evidence is reported.

The record does not report how missing outcome data were handled, whether any imputation was used, or what rules determined inclusion in each analysis. It also does not name the primary analysis population. The population field for the primary outcome is blank. The primary outcome summaries list 76 participants for Polyoxidonium and 79 for placebo, while total enrollment is 172. These entries do not establish the reasons for the difference or whether all randomized participants were included in the relevant analyses.

The registry record does not report interim analyses, stopping rules, a sample-size justification for the trial’s original design, or a detailed statistical analysis plan. The planning illustrations associated with selected secondary outcomes are explicitly based on observed effects and stated assumptions; they do not establish the trial’s original planning rationale. Such details matter because they can clarify which analyses were prespecified, how missing observations were treated, and how multiple results were intended to be interpreted.

These omissions do not prove that a particular procedure was or was not used outside the registry record. They mean that the record does not give enough information to assess those procedures. The primary result should be read with the reported uncertainty and the p-value/interval inconsistency, while the secondary findings should be treated as exploratory or descriptive unless additional analysis documentation 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 non-serious adverse event terms

The adverse-event summaries list 84 participants at risk in the Polyoxidonium group and 86 in the placebo group. Serious adverse events are reported for 0 participants in each group, and deaths are reported for 0 in each group. The registry lists other adverse events affecting 1 participant in the Polyoxidonium group and 6 in the placebo group.

These counts describe the entries posted in the registry; they do not, on their own, establish a comparative safety profile. The record does not provide the serious-event terms, event severity details beyond the serious/non-serious categories, duration of follow-up for safety, or a statistical comparison of adverse-event rates. The serious-event term list is empty. A count of zero in these groups means no such events are listed in the posted summaries, not that risk is absent.

The adverse-event denominators differ from the denominators in the primary outcome summaries. The registry record does not explain the difference, so the two sets of counts should not be treated as if they used the same analysis population. The summaries are descriptive and should be interpreted within the limits of the information the registry reports.

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

The posted data show a lower observed mean fever duration in the Polyoxidonium group than in the placebo group: 2.04 days compared with 2.26 days. The reported mean difference is -0.22 days. These are summaries of the trial groups, not guarantees about an individual participant’s course.

The uncertainty around the difference is important. The reported 95% confidence interval extends from -0.6 to 0.16, which includes zero and values in either direction. The primary outcome also names a superiority cut-off of δ=-0,52 days; the reported point estimate does not reach that cut-off. At the same time, the registry lists p <0.05 for its two-sided t-test. Because that statement is inconsistent with the interval as posted, the record does not provide one unambiguous statistical account of the primary result.

The secondary outcomes describe additional measures, but they do not erase the primary uncertainty. Their interpretation is further limited by multiple comparisons, the absence of a reported multiplicity approach, and differences between some registry p-values and unadjusted recalculations. The registry also does not report the primary analysis population or the handling of missing outcome data.

Accordingly, the results describe what was recorded for this randomized comparison, along with substantial uncertainty and reporting limitations. They do not establish from the registry record alone that the stated superiority criterion was met, nor do they resolve the conflict between the reported p-value and confidence interval. No conclusion about what an individual should do follows from these statistics.

14. Why This Trial Matters Statistically

This trial illustrates why a primary result should be read through several linked elements: the outcome definition, the effect estimate, its confidence interval, the test result, and any decision threshold specified for superiority. Looking only at the direction of the group means would miss the uncertainty in the interval. Looking only at the p-value would miss that the posted interval includes zero and that the primary outcome states a particular cut-off.

It also demonstrates the value of distinguishing a difference between means from a threshold-based superiority question. A point estimate can favor one group without reaching the stated threshold, and an interval can include estimates with different implications. Clear reporting of the threshold’s rationale and the decision rule would help readers understand how the statistical question was intended to be answered; those details are not reported in the registry record.

The secondary results show why a collection of outcomes should not be read as a set of independent confirmations. Several measures address related but distinct aspects of the clinical course, and multiple unadjusted comparisons can complicate interpretation. A prespecified hierarchy or multiplicity method can clarify which comparisons are confirmatory and how secondary evidence should be weighed. Such an approach is not reported in the registry record.

Finally, the difference between total enrollment and the posted primary outcome denominators, together with the absence of information about analysis populations and missing data, highlights the importance of participant-flow and analysis details. These are not minor bookkeeping points: they help readers understand who contributed to each result and how robustly the findings represent the randomized groups. The record supports a careful description of the posted results, but leaves important statistical details unresolved.

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.

Several limitations specific to this registry record affect interpretation. First, the primary analysis has a reported two-sided p-value of p <0.05 alongside a 95% confidence interval from -0.6 to 0.16 that includes zero. The record does not explain this mismatch. The primary point estimate, -0.22 days, also does not reach the stated superiority cut-off of δ=-0,52 days. These issues make it difficult to interpret the registry’s superiority label without further analysis documentation.

Second, the primary outcome population is not specified in the record, and handling of missing observations is not reported. The primary summaries list 76 participants for Polyoxidonium and 79 for placebo, while enrollment is 172. Participant flow and the reasons for the difference are not reported in the information. Safety summaries use different denominators, and the record does not explain the relationship between those denominators and the primary outcome population.

Third, the record lists 11 secondary measures but posts results for 10. It does not report a multiplicity correction, testing hierarchy, original sample-size justification, interim analyses, or detailed statistical analysis plan. The secondary calculations are unadjusted, and selected posted p-values do not align with those recalculations. These factors reduce the strength of conclusions drawn from individual secondary results.

Finally, the registry provides limited detail for independently assessing the primary test. It does not post primary-group dispersion values or the randomization procedure, and it does not identify the roles included in triple masking. The record also provides limited detail on adverse-event terms and safety follow-up. These omissions do not establish that procedures were absent, but they restrict what can be verified from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Polyoxidonium, Nasal and Sublingual Spray, 6 mg/ml in Children Aged 1-12 Years With ARI — NCT03840135.
• Registry record last updated 2020-07-29; status last verified 2020-07.
• Results first posted 2020-06-25.
• 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 describes a completed, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group phase 3 study of Polyoxidonium nasal and sublingual spray in children aged 1 to 12 years with acute respiratory infection. Enrollment was 172. The intervention was described as 0,15 mg/kg daily for 7 days; placebo spray was also given for 7 days.

The primary outcome was mean fever duration at Day 8±1. The reported means were 2.04 days and 2.26 days, with a reported mean difference of -0.22 days and a 95% confidence interval from -0.6 to 0.16. The registry reports p <0.05 for a two-sided t-test, although that statement is inconsistent with the interval as posted. The stated superiority cut-off is δ=-0,52 days.

The record posts results for 10 of 11 listed secondary measures. It does not report the primary analysis population, missing-data handling, multiplicity approach, or detailed analysis plan. Serious adverse events and deaths are listed as 0 in both groups; other adverse events are listed for 1 participant in the Polyoxidonium group and 6 in the placebo group.