Povidone-Iodine Oral Rinse Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Povidone-Iodine Oral Rinse Study (NCT05239598), a randomized phase 2 study. The primary outcome is [PCR Saliva] Percent Change From Baseline Ct Viral Targets.

2. Clinical Question

3. Trial Design

The registry describes a Phase II randomized trial with a parallel model and triple masking. Its brief summary describes a two-arm, two-phase study: Phase I as a double-blinded clinical trial of mouthwash safety and efficacy, followed by Phase II as an open-label trial in which all subjects receive active mouthwash. These descriptions indicate that masking differed across the described phases; the registry record does not provide further detail on how the masking classification applies across the whole study.

The randomized comparison was between povidone-iodine 0.5% antiseptic mouth rinse and placebo. The registry states that participants were randomized in a 1:1 ratio. The reported primary endpoint analysis includes 19 participants in the povidone-iodine group and 17 in the placebo group. The record lists an overall enrollment of 40, but the endpoint analysis population differs because some observations were excluded or missing.

The intervention was a single rinse or gargle of 10 mL for 30 seconds. The primary endpoint was measured 60 minutes after intervention. The registry also lists a secondary outcome concerning percentage change from baseline Cycle Threshold at 5 and 30 minutes after intervention. The study status is completed, with a start date of 2022-02-07 and primary completion date of 2022-07-07. The record does not report a detailed account of how participants moved between phases or how Phase II participants relate to the randomized endpoint groups.

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.

Phase I

Phase II (Open Label)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants were randomized to Povidone-iodine or Placebo (saline) in a 1:1 ratio. Three participants had non-evaluable baseline Cycle Threshold-values and one value was missing at 60 minutes so they were excluded from the analysis of the outcome.

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 [PCR Saliva] Percent Change From Baseline Ct Viral Targets, measured over 60 minutes after intervention.

The primary endpoint is the percentage change from baseline in saliva Cycle Threshold for SARS-CoV-2 viral targets, assessed 60 minutes after intervention. Cycle Threshold, or Ct, is a PCR measure used as a proxy for viral load. The registry explains that a positive percentage change from baseline Ct indicates a decrease from baseline SARS-CoV-2 load. Thus, the endpoint translates a laboratory measurement into a change-from-baseline measure intended to describe the direction and magnitude of viral-load change.

The endpoint is useful for comparing the two randomized groups at a specified time after the rinse. It does not directly count viral particles or establish whether virus can be transmitted. Its interpretation depends on the stated Ct proxy and on the way percentage change is defined and measured. The registry names the Quick SARS-CoV-2 rRT-PCR Kit as the assay used.

The reported group means were 5.8 for povidone-iodine and 1.3 for placebo. The corresponding 95% confidence intervals were 0.8 to 10.7 and -6.2 to 8.8. The sponsor’s reported comparison is a net mean difference at the 60-minute endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a two-sided t-test for the primary comparison. The outcome is continuous, and the reported parameter is the net mean difference between the povidone-iodine and placebo groups. A mean summarizes the central value of a continuous measure; the net mean difference expresses how far apart the two group means are on the outcome scale. The sponsor’s reported difference is 4.5 percentage-change units.

What does the confidence interval convey?

A confidence interval describes the uncertainty around an estimated effect under the statistical model and sampling procedure. In general, a wider interval indicates less precision than a narrower interval. The reported 95% confidence interval for the net mean difference extends from -4.0 to 13.0. Because it includes zero, the data do not distinguish the estimated difference from no difference at the conventional level associated with this interval. The interval also includes positive and negative values, so the direction of the underlying difference is uncertain.

The group-specific intervals are not substitutes for the interval around the difference. The povidone-iodine group mean has a 95% confidence interval from 0.8 to 10.7, and the placebo group mean has a 95% confidence interval from -6.2 to 8.8. A direct comparison should use the sponsor’s interval for the net difference, because that interval incorporates uncertainty in the comparison itself.

Why use a t-test?

A t-test is a method for comparing means. In general, its interpretation depends on the data and assumptions appropriate to the analysis, including how observations were sampled and whether the chosen model adequately represents their variability. The registry names a two-sided t-test but does not report further detail on the particular t-test formulation, assumption checks, or any adjustment to the comparison. Those details are not reported in the registry record.

A two-sided test evaluates departures in either direction rather than prespecifying only an increase or only a decrease. The p-value is 0.287. It should be read alongside the estimated difference and confidence interval: the p-value alone does not measure effect size or precision, and it does not show the probability that the null hypothesis is true.

What does the endpoint scale mean?

The outcome is percentage change from baseline Cycle Threshold, and the registry specifies that a positive value indicates a decrease from baseline SARS-CoV-2 load. Ct is a proxy, not a direct count of infectious virus. A change in this laboratory measure therefore should not be interpreted as a direct measure of transmission or clinical outcome. The assay named in the record is the Quick SARS-CoV-2 rRT-PCR Kit.

The primary measure is continuous, so the reported mean and confidence interval summarize values on a numeric scale. The record does not report a measure of dispersion for each group in the posted outcome entry. Without further information about the distribution of individual observations, the summary means alone cannot show how observations varied within each group or whether there were unusual values. The registry’s reported t-test remains the sponsor’s stated analysis.

What does the planning illustration represent?

In general, a sample-size calculation asks how many participants might be needed under specified assumptions to detect a target effect with a chosen significance level and power. The registry’s planning illustration is based on the observed effect, a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such estimates are planning illustrations, not observed power and not evidence that the trial had a particular probability of detecting an effect. The record does not report the trial’s own sample-size justification, so the planning assumptions should not be treated as the protocol’s original design basis.

The record describes a randomized comparison, which supports a between-group interpretation of the reported outcome, but the available information does not establish all details of allocation implementation or analysis conduct. A statistical result is conditional on its outcome definition, measured time, included population, and analysis method. Those features matter when comparing this estimate with results from other studies or time points.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s two-sided t-test comparing mean percentage change in Cycle Threshold between the randomized groups. The reported net mean difference is 4.5, with a 95% confidence interval from -4.0 to 13.0 and p = 0.287. No discrepancy between the posted summary and the sponsor’s reported analysis is flagged in the registry record.

A separate recalculated comparison is not reported in the registry record. The record indicates that values were missing or not estimable for a two-arm comparison of this continuous endpoint. Accordingly, the sponsor’s own analysis is the available inferential result to interpret; no independent recalculated estimate should be substituted for it. The group means and confidence intervals remain useful descriptive summaries, but they do not by themselves provide a replacement test of the between-group difference.

The sponsor’s test concerns the specified 60-minute endpoint and analysis population. It does not establish what would be observed at other time points or for other outcomes. The confidence interval and p-value should be read together: the test does not meet a conventional significance threshold, while the interval also indicates uncertainty about the magnitude and direction of the between-group difference.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, 15 analyses, and one posted secondary outcome. The posted secondary outcome concerns percentage change from baseline Cycle Threshold at 5 and 30 minutes after intervention. Because multiple outcomes or analyses can create multiple opportunities to observe apparently notable results, interpretation can depend on whether the analysis plan addressed multiplicity. A multiplicity adjustment or a prespecified hierarchy among outcomes is not reported in the registry record.

The primary endpoint analysis excluded three participants with non-evaluable baseline Cycle Threshold values and one value missing at 60 minutes. The endpoint entry therefore does not describe an analysis of every enrolled participant. The record does not report the reasons for those non-evaluable or missing values, whether missingness was related to treatment or outcome, or whether any sensitivity analysis assessed the effect of missing data. It also does not report an imputation method.

The registry identifies the endpoint population as randomized participants, then describes the exclusions for this outcome. More detail on the analysis population, including whether an intention-to-treat principle was applied to other analyses, is not reported in the registry record. The group sizes reported for the primary outcome are 19 for povidone-iodine and 17 for placebo. Those are the relevant posted group counts for interpreting this endpoint, rather than the overall enrollment figure.

The record names a two-sided t-test but does not report whether covariates were included, whether an adjusted analysis was conducted, how assumptions were assessed, or how multiplicity was handled. These omissions do not invalidate the reported estimate, but they limit assessment of how the analysis was planned and how robust the result may be to alternative choices. The primary result is best interpreted as the sponsor-reported comparison for the stated outcome, time point, and included observations.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for the randomized povidone-iodine and placebo groups as zero affected among 20 at risk in each group. For the open-label Phase II group, it reports zero serious adverse events among 37 at risk. Deaths are reported as zero for all three listed groups. No serious adverse-event terms are listed.

These are registry counts for the specified groups and adverse-event categories. They do not establish that no other symptoms or events occurred, and they do not quantify risks beyond the recorded observation periods. The record separately reports other adverse events: zero affected among 40 at risk in each of the randomized treatment categories, and four affected among 37 at risk in the Phase II open-label group. These figures should not be combined with serious adverse-event counts, because the record lists them as different categories and with different at-risk counts.

The registry does not report additional details in this entry about event definitions, severity breakdowns, timing, relatedness, or follow-up duration. Safety counts should therefore be read as the reported event record, rather than as a complete characterization of tolerability or evidence about rare events.

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

The posted results estimate the difference between povidone-iodine and placebo in percentage change from baseline saliva Cycle Threshold at 60 minutes. The sponsor reported a net mean difference of 4.5, with a 95% confidence interval from -4.0 to 13.0 and p = 0.287. The interval includes zero and includes effects in either direction. The estimate is therefore uncertain, and the reported comparison does not provide clear evidence of a between-group difference at this endpoint and time point.

This finding should not be translated into a claim that the mouth rinse works or does not work. A non-significant test does not establish equivalence, and the interval leaves room for effects other than zero. Conversely, a positive group mean does not establish a treatment effect: the treatment question is addressed by comparing the randomized groups, not by considering one group’s change in isolation.

The measured outcome is a PCR Cycle Threshold proxy for SARS-CoV-2 load in saliva. The record defines a positive percentage change as a decrease from baseline load. It does not report a direct measure of infectious virus, transmission, infection control in practice, or clinical outcomes. The result therefore applies to the stated laboratory measure and 60-minute assessment, not to those broader questions.

The endpoint analysis excludes participants with non-evaluable baseline values and a missing 60-minute value. The reasons and consequences of those missing observations are not reported in the registry record. The sample and outcome summary also provide limited detail about variability and analytic choices beyond the reported t-test. These points restrict how broadly the result can be generalized or how confidently it can be compared with other settings.

14. Why This Trial Matters Statistically

This trial is statistically informative because it makes the distinction between within-group change and a randomized between-group comparison especially important. The group means are 5.8 for povidone-iodine and 1.3 for placebo, but the treatment contrast is the sponsor-reported net mean difference, with its own confidence interval and test. Looking only at whether either group’s mean is positive would not answer the randomized comparison question.

The result also illustrates why uncertainty matters alongside a point estimate. The reported difference is 4.5, while its 95% confidence interval extends from -4.0 to 13.0. That interval includes no difference and a range of possible effects in either direction. The p-value of 0.287 cannot summarize this range or establish that effects are equivalent. Reporting both the estimate and interval gives a fuller account of the evidence than a significance label alone.

Endpoint definition also shapes interpretation. Here, Cycle Threshold is a proxy for SARS-CoV-2 load, and the primary assessment is at 60 minutes. A laboratory proxy at a single specified time is not interchangeable with a clinical outcome or evidence about infection control in dental practice. The meaning of the result must remain tied to that measure and time point.

Finally, the registry describes multiple outcome measures and analyses, but does not report multiplicity handling or a full statistical analysis plan. It also identifies missing or non-evaluable endpoint observations. These are practical reminders that estimates depend on outcome selection, analysis population, and handling of incomplete data. The posted result is most useful when read with those design and reporting limits in view.

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 primary endpoint analysis excludes three participants with non-evaluable baseline Cycle Threshold values and one missing value at 60 minutes. The registry record does not explain why these values were unavailable or report sensitivity analyses for missing data. This leaves uncertainty about whether the analyzed observations fully represent the randomized groups for this outcome.

The registry reports a t-test and summary estimates but does not provide further detail on the test formulation, assumption checks, or any covariate adjustment. A measure of dispersion for each group is not reported in the endpoint entry. This limits independent assessment of the data distribution and of the analysis choices. A separate recalculated two-arm comparison is not reported because values are marked as missing or not estimable for that purpose.

The record describes the trial as triple masked while its brief summary describes Phase I as double blinded and Phase II as open label. It does not explain how the overall masking classification relates to the phases. The phase-specific conduct and the relationship of open-label participants to the randomized comparison are therefore not fully described in this record.

The outcome is a saliva PCR Cycle Threshold proxy assessed at 60 minutes. The registry does not report a direct measure of infectious virus, transmission, or clinical outcomes. Although a secondary outcome is listed for 5 and 30 minutes, the registry does not provide a fuller account of the timing and analysis plan across outcomes. Multiplicity handling is not reported in the registry record.

The listed sample-size illustration uses the observed effect and specified planning assumptions; it is not the trial’s own design justification. The registry record does not report the original sample-size rationale or interim-analysis plan. The findings should therefore be understood as the posted endpoint analysis and not as a complete account of all design and analysis decisions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Povidone-Iodine Oral Rinse Study — NCT05239598.
• Registry record last updated 2023-08-14; status last verified 2023-07.
• Results first posted 2023-08-14.
• 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 II randomized, parallel study of povidone-iodine 0.5% mouth rinse versus placebo in adults with COVID-19. The overall enrollment is listed as 40. The primary endpoint is percentage change from baseline saliva Cycle Threshold at 60 minutes, with positive values defined as indicating a decrease from baseline SARS-CoV-2 load.

The primary outcome analysis includes 19 participants in the povidone-iodine group and 17 in the placebo group. Their reported means are 5.8 and 1.3, respectively. The sponsor’s reported net mean difference is 4.5, with a 95% confidence interval from -4.0 to 13.0 and a two-sided p-value of 0.287. The interval includes zero and leaves uncertainty about the direction and magnitude of the difference.

The outcome analysis excluded non-evaluable baseline values and a missing 60-minute value. The registry also lists a secondary outcome at 5 and 30 minutes, while multiplicity handling and additional analysis details are not reported. Serious adverse events and deaths are recorded as zero in the listed groups.