Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Acute Respiratory Viral Infections in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Acute Respiratory Viral Infections in Children (NCT03039621), a randomized phase 4 study. The primary outcome is Time to Alleviation of All ARVI Symptoms..

2. Clinical Question

3. Trial Design

This was a phase 4, randomized, quadruple-masked, parallel-group study comparing Ergoferon with placebo. The official title describes it as international, multicenter, double-blind, placebo-controlled, and randomized. The sponsor was Materia Medica Holding. The record lists the study status as completed, with a start date of 2016-10-07 and a primary completion date of 2019-01-09.

The stated objective was to obtain additional data on the efficacy and safety of Ergoferon in children aged from 6 months to 6 years old with acute respiratory viral infections. The intervention description specifies oral tablets and outlines a day 1 schedule followed by dosing every 8 hours from day 2. The final portion of that description is truncated in the registry record. The placebo is described as using the Ergoferon scheme.

The primary endpoint was assessed in the ITT sample and had a 14 days of observation timeframe. The posted arm summaries list 140 for Ergoferon and 142 for placebo. These are the endpoint group counts, not an explanation of participant flow. Although enrollment is recorded as 287, a flow diagram, exclusions, and reasons for any difference between enrollment and endpoint counts are not reported in the registry record.

The registry names several secondary outcomes, including temperature normalization, alleviation of symptom groups, symptom scores, severity, recovery, antipyretic use, and worsening of illness. It records 9 outcome measures and 10 analyses. The randomization sequence, allocation concealment, the identities of the masking roles, adherence procedures, and details of the study sites are not reported in the registry record. Nor is a protocol or statistical analysis plan described in the 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: ITT sample

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 Time to Alleviation of All ARVI Symptoms., measured over 14 days of observation..

The primary endpoint was time to alleviation of all acute respiratory viral infection symptoms, measured in days over 14 days of observation. It was based on patient diary data. The registry definition required oral temperature at or below 37.5С for 24 hours, without a later increase within the observation period, together with either no symptoms or symptoms whose total score was no more than 3 points.

The symptom score used a 4-point scale for each flu-like nonspecific and respiratory symptom: 0 meant no symptom, 1 mild, 2 moderate, and 3 severe. The combined total score ranged from 0 to 30, with higher scores indicating a worse outcome. The endpoint therefore combines temperature and symptom burden in a time-based measure. This can describe how quickly participants met the trial’s specified alleviation criteria, rather than only capturing symptom status at a single visit.

The endpoint is useful for comparing the timing of a defined clinical state, but its meaning depends on the diary records and on the operational definition of alleviation. It does not by itself describe every dimension of illness, such as each symptom separately or the course after the observation period. The registry reports group means with 95% confidence intervals, while the reported comparison is a Wilcoxon (Mann-Whitney) test. Further details about diary completion, handling of incomplete diary data, or confirmation of the endpoint are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports means for the primary continuous endpoint and 95% confidence intervals for each group. A mean is an average on the measured day scale. A confidence interval expresses uncertainty around an estimate under the statistical procedure used to construct it. It is not a range containing every participant’s observed time, and it does not show the amount of variation among individual participants. The registry does not post a standard deviation or other measure of within-group spread for this endpoint.

What does the primary comparison test?

The reported primary method is the Wilcoxon (Mann-Whitney) test. In general, this is a rank-based method: it uses the ordering of observations to assess whether values in one group tend to be higher or lower than values in the other. It does not directly test whether the two arithmetic means are equal. The mean summaries and the rank-based test thus answer related but not identical questions. The registry’s p-value is 0.026; a test statistic and details of the test implementation are not reported in the registry record.

Rank-based methods can be useful when an outcome’s distribution is not well represented by a simple normal model. Their interpretation is not automatically a comparison of medians, however. If group distributions differ in shape or spread, a rank-test result can reflect more than a location shift. General statistical interpretation should therefore consider the endpoint distribution and the estimand of interest. Distribution plots or additional descriptive summaries for the primary outcome are not reported in the registry record.

How should confidence intervals be read?

Each group’s 95% confidence interval describes uncertainty in that group’s mean estimate, not uncertainty in the between-group contrast. A direct interval for the difference in mean time, or for another explicitly defined treatment contrast, is not reported in the registry record. General statistical practice is to assess the contrast itself when the question concerns how groups differ. Comparing the endpoints of separate group intervals is not a substitute for a confidence interval for that contrast.

The endpoint is a time measure, but the registry gives a mean and a rank-based test. The methods used to account for participants who did not meet the criteria during observation, had incomplete diary data, or otherwise lacked an observed event are not reported in the registry record. These details matter because time-to-event analyses often require explicit definitions of the event, censoring, and follow-up. The record does not identify a time-to-event method for the primary analysis, so such a method should not be assumed.

How does the secondary binary result differ?

For worsening of illness, the registry reports counts of participants in each group and a Fisher Exact test. Fisher’s test is a method for comparing categorical outcomes, particularly when counts are limited. The reported sponsor analysis has p < 0.001. The recalculated unadjusted risk difference is -0.127 with a 95% confidence interval from -0.184 to -0.069, and its unadjusted p-value is < 0.001. A risk difference expresses a difference in event risk between groups on an absolute scale; the sign depends on which group is subtracted from which. The registry’s comparison identifies Ergoferon as the arm for the recalculated contrast.

The recalculated result is an unadjusted calculation from the posted group counts, not a replacement for the sponsor’s analysis. The two p-values arise in the context of the reported Fisher Exact analysis and the unadjusted recalculation, respectively. No adjustment for covariates is described. General cautions apply to unadjusted comparisons: randomization supports a group comparison, but unadjusted results do not address every possible analytic choice or missing-data issue.

What do the planning illustrations mean?

The sample-size illustrations are planning calculations based on the observed effect, not the trial’s own design justification and not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation; for the binary outcome, the effect to detect is expressed as a fraction of the observed effect. For planning for 100% of the observed effect, the illustration gives 63 participants per arm for 80% power and 84 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 136 participants per arm for 80% power and 182 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 358 participants per arm for 80% power and 479 participants per arm for 90% power.

These figures are hypothetical planning illustrations. They do not show the probability that this completed trial detected an effect, and they do not establish the assumptions used when the trial was designed. The sample-size justification and the trial’s own power calculation are not reported in the registry record. General planning methods depend on the target effect, outcome variability or event rate, significance level, allocation, and analysis method; changing an assumption changes the resulting planning requirement.

10. Analyses Reported by the Sponsor

For the primary endpoint, the sponsor-reported analysis is the Wilcoxon (Mann-Whitney) test with p = 0.026. The registry also posts group means and 95% confidence intervals: 4.5 days for Ergoferon, with an interval of 4.2 to 4.8, and 5.2 days for placebo, with an interval of 4.8 to 5.6. No recalculated primary contrast is posted in the record, so there is no recalculated estimate to set against the sponsor’s test. The sponsor’s analysis remains the reported primary analysis.

For worsening of illness, the sponsor’s reported method is Fisher Exact, with p < 0.001. The unadjusted recalculation from posted summary counts gives a risk difference of -0.127, a 95% confidence interval from -0.184 to -0.069, and p < 0.001. The recalculation supplies a different form of summary, including an absolute contrast and interval, while the registry’s sponsor analysis supplies the Fisher Exact p-value. These should be read as analyses with their stated methods, rather than as identical estimates.

The registry marks no discrepancy between the reported and recalculated results. That does not make the recalculation a substitute for the sponsor’s analysis or provide additional information about the protocol. Details of any adjusted model, sensitivity analysis, or prespecified analysis hierarchy are not reported in the registry record. The planning illustrations are also separate from both sets of results: they are not observed power and do not identify the sponsor’s design assumptions.

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary endpoint and multiple secondary outcomes, but the statistical approach to multiplicity is not reported in the registry record. Multiplicity arises when several hypotheses are tested: the more tests considered, the greater the chance that some appear statistically notable by chance alone. General approaches include prespecifying a hierarchy, adjusting the threshold or p-values, or treating secondary analyses as exploratory. The record does not say whether any such approach was planned or used.

The registry lists 8 secondary outcomes and records 10 analyses. Those counts do not, by themselves, reveal which comparisons were prespecified, how outcomes were grouped into testing families, or whether the primary analysis was protected from secondary testing. A p-value for an individual secondary comparison should therefore not be interpreted as adjusted evidence across all secondary outcomes. A protocol or statistical analysis plan that could clarify these matters is not reported in the registry record.

The primary analysis population is identified as the ITT sample. The record does not define the precise ITT population, state how participants were handled if they did not follow their assigned regimen, or describe exclusions from the endpoint analysis. Although enrollment is recorded as 287 and the primary endpoint arm counts are 140 and 142, participant flow and the reasons for any differences are not reported in the registry record. These values should not be combined to infer an unreported analysis population.

Missing-data handling is not reported in the registry record. In general, missing diary entries can affect an endpoint based on time to a diary-defined event, while missing outcome status can affect a binary comparison. The record does not describe imputation, censoring, complete-case analysis, sensitivity analyses, or assumptions about why observations might be missing. Without that information, the robustness of the estimates to incomplete observations cannot be assessed.

The registry reports a primary p-value and endpoint confidence intervals, but does not report a primary contrast interval, a test statistic, or a full analysis model. It also does not report interim analyses or stopping rules. Those items should not be inferred from the completed status or from the posted results.

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 registry safety figures list 0 serious adverse events affecting participants in the Ergoferon group and 0 in the placebo group. For other adverse events, the record lists 10 affected participants in the Ergoferon group and 27 in the placebo group. These figures are counts, and the record does not provide event-level descriptions for the non-serious category or the follow-up and attribution details needed for a fuller comparison. No top serious adverse-event terms are listed.

The safety summary also contains values of 10 and 27 in fields labeled deaths, for Ergoferon and placebo respectively. These values match the listed counts for other adverse events, but the registry record does not clarify their meaning or relationship. They should not be interpreted as a verified death count without clarification from the record. This apparent overlap makes the safety fields difficult to interpret and should be treated as a data-reporting limitation.

Zero reported serious adverse events does not establish that no serious events could occur, and raw counts alone do not measure comparative risk precisely. The registry does not report exposure-adjusted rates, event timing, causality assessments, or a detailed safety analysis. These posted figures are therefore a limited summary, not a complete assessment of safety.

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

The primary results describe a difference in the posted group summaries for time to meeting the registry’s symptom-alleviation criteria. The Ergoferon group mean was 4.5 days, while the placebo group mean was 5.2 days; the reported rank-based comparison had p = 0.026. The figures indicate the direction and uncertainty of the group summaries, but they do not provide a confidence interval for the between-group contrast. They also do not describe the experience of every participant.

The worsening outcome is a separate secondary measure. Its posted counts and unadjusted recalculation describe the comparison for that outcome, not the full range of symptoms or the primary endpoint. Because the registry does not report the results for the other listed secondary outcomes in the registry record for this analysis, consistency across the full outcome set cannot be determined. Multiplicity procedures are not reported, which limits the confirmatory interpretation of secondary tests.

These results do not establish the mechanism behind any observed group difference, how the outcome might change outside the trial’s observation period, or whether the findings apply to populations other than children aged from 6 months to 6 years old. The registry record also does not provide the details needed to evaluate missing data, participant flow, or adherence fully. Statistical results depend on how outcomes are defined and analyzed, and the endpoint depends on diary-based criteria.

In general, a p-value is not a measure of clinical importance, and a confidence interval is not a guarantee that the true value lies within its endpoints. The statistical evidence should be read alongside the outcome definition, study conduct, and completeness of reporting. The posted results are evidence about the analyses recorded for this trial; they are not, on their own, a complete account of benefits, harms, or applicability.

14. Why This Trial Matters Statistically

This trial illustrates why it is important to distinguish the outcome summary from the statistical test. The primary endpoint is presented as group means with confidence intervals, yet the reported test is rank-based. A reader who treats the p-value as a direct test of the difference between means would misstate what the analysis evaluates. Clear reporting of the estimand, the contrast, and its uncertainty would help align the statistical question with the clinical question.

The endpoint also shows how composite criteria can make a time-based outcome more interpretable while introducing dependence on operational definitions. Here, alleviation combines a temperature condition with symptom status or a symptom-score threshold, using patient diary data. The interpretation therefore depends not only on elapsed time but also on how consistently those criteria were recorded and how incomplete observations were handled. Those implementation details are not reported in the registry record.

The secondary worsening analysis illustrates the distinction between a sponsor-reported test and an unadjusted recalculation. A p-value and an absolute risk-difference estimate answer related but different reporting needs. The planning illustrations further show why planning assumptions must be separated from trial results: they are hypothetical calculations based on the observed effect and do not describe observed power or the trial’s original design justification.

Finally, the record demonstrates the importance of complete statistical reporting. Information about multiplicity, participant flow, missing-data methods, and safety-field interpretation would materially assist readers in judging how robust and comprehensive the posted evidence is. These are general lessons for interpreting registry results, not claims that any particular unreported procedure was or was not carried out.

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 trial-specific reporting gaps limit interpretation. The primary endpoint is based on patient diary data, but the registry does not describe diary completion, validation, or how incomplete records were handled. It gives arm means and confidence intervals but no direct interval for the between-group contrast. A rank-based test is reported without its test statistic or fuller distributional summaries, so the relationship between the test result and the displayed means cannot be examined in detail.

The record identifies the primary population as ITT but does not define its membership or describe participant flow. Enrollment is 287, while the primary endpoint counts are 140 for Ergoferon and 142 for placebo; the reason for the difference is not reported in the registry record. Details about exclusions, adherence, withdrawals, and missing outcomes are also not reported. These omissions make it difficult to assess whether the posted analysis includes all randomized participants as intended.

Although the study is described as randomized and quadruple-masked, the sequence-generation method, allocation concealment, and masking roles are not reported in the registry record. The protocol, statistical analysis plan, sample-size justification, interim analyses, and stopping rules are not reported either. These details would help establish which analyses were planned and how faithfully the reported analyses reflect that plan.

The registry lists several secondary outcomes but does not report numerical results for most of them in the available record. It also does not report a multiplicity strategy, limiting the confirmatory interpretation of secondary findings. Finally, the safety summary includes values under the deaths label that match the other-adverse-event counts, with no clarification; this prevents confident interpretation of that field.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Acute Respiratory Viral Infections in Children — NCT03039621.
• Registry record last updated 2021-08-27; status last verified 2019-05.
• Results first posted 2020-04-27.
• 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 phase 4, randomized, quadruple-masked, parallel-group trial sponsored by Materia Medica Holding. It compared Ergoferon with placebo in children aged from 6 months to 6 years old with acute respiratory viral infections. Enrollment is recorded as 287.

The primary endpoint was time to alleviation of all acute respiratory viral infection symptoms over 14 days of observation, based on patient diary data. The posted means were 4.5 days for Ergoferon and 5.2 days for placebo, with respective 95% confidence intervals of 4.2 to 4.8 and 4.8 to 5.6. The reported Wilcoxon (Mann-Whitney) p-value was 0.026.

The registry lists secondary outcomes and a worsening comparison, but does not report a multiplicity approach, missing-data methods, or participant flow. Safety figures include no reported serious adverse events in either group, alongside other adverse-event counts and an ambiguous deaths field. These reporting limitations qualify interpretation of the posted results.