Therapeutic Effects of "Ibuprofen, Diphenhydramine and Aluminium MgS" on Recurrent Aphthous Stomatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Therapeutic Effects of "Ibuprofen, Diphenhydramine and Aluminium MgS" on Recurrent Aphthous Stomatitis (NCT01293968), a randomized phase 2 study. The primary outcome is Effect of Ibuprofen, Diphenhydramine and Aluminium MgS Measured on Decrease in Pain Level and Burning Sensation.

2. Clinical Question

The study aim was to assess whether the combinations decreased signs of RAS. The primary outcome is described as the effect of ibuprofen, diphenhydramine and Aluminium MgS on decrease in pain level and burning sensation, measured using scores on a Visual Analogue Scale. The scale description identifies zero as the point for no pain and the 10th point as maximum pain. The assessment was recorded four days after the start of the study, also described as four days after consumption of the solution.

The clinical contrast is the addition of ibuprofen to a combination of diphenhydramine and Aluminium MgS. Because both arms contain diphenhydramine and Aluminium MgS, the results do not compare the full combination with no treatment. Nor does the record establish how the two combinations compare with usual care or another treatment. The posted arm means describe pain scores at the assessment time; they do not, by themselves, quantify a randomized between-arm effect. A registry-reported comparison estimate and its uncertainty are not reported in the registry record.

The record lists a secondary outcome concerning pain level and burning sensation, but it does not provide a separate posted result for burning sensation. The clinical question that can be addressed from the reported numbers is therefore narrow: what arm-specific pain means and confidence intervals were recorded at the stated follow-up time? Whether the treatments caused a difference, whether pain changed from baseline, and what happened to other signs of RAS cannot be determined from these estimates alone.

3. Trial Design

The registry record describes a completed, randomized, double-masked, parallel phase 2 study sponsored by Qazvin University Of Medical Sciences. The recorded study start is 2010-11, and the primary completion is 2011-01. Enrollment is listed as 37. These design labels describe the intended structure, but the record does not report the randomization procedure, allocation ratio, concealment method, or which people were masked.

The two arms received different drug combinations. One arm is identified as ibuprofen, diphenhydramine and Aluminium MgS; the other received diphenhydramine and Aluminium MgS. The comparator therefore shares two named components with the intervention. The registry record does not describe a placebo group. Arm descriptions include solution amounts and concentrations, but do not explain treatment administration or adherence in further detail.

The primary outcome is a mean score on a Visual Analogue Scale, with a 95% confidence interval, assessed four days after study start. The registry record reports 17 participants for the ibuprofen-containing arm and 14 for the comparator arm for this outcome. Those arm-specific outcome counts do not account for the enrollment figure of 37 in the posted endpoint results; the reason for the difference is not reported in the registry record. The record does not state whether the outcome counts represent all randomized participants, participants treated, or participants with observed endpoint data.

Although the study is marked completed, the registry record does not provide a detailed protocol or statistical analysis plan. It does not report the planned allocation ratio, planned sample-size justification, interim analyses, analysis population, or approach to missing observations. The word intention in the study aim refers to the purpose of studying effects; it does not establish that an intention-to-treat analysis was performed. These gaps limit how fully the design and analysis can be reconstructed from the registry entry.

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: The intention of the study is to study the effects of Ibuprofen, Diphenhydramine and Aluminium MgS in decreasing the signs of RAS

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 Effect of Ibuprofen, Diphenhydramine and Aluminium MgS Measured on Decrease in Pain Level and Burning Sensation, measured over four days after the start of the study.

The primary endpoint is described as a decrease in pain level and burning sensation measured by scores on a Visual Analogue Scale. The scale description explains that zero indicates no pain and the 10th point indicates maximum pain. The posted result is expressed as an arm-specific mean score with a 95% confidence interval, assessed four days after the start of the study.

A Visual Analogue Scale turns a subjective symptom rating into a quantitative measure. In general, such a score can help describe symptom intensity in a consistent format, while the mean summarizes the average score among the participants represented in that arm's result. Since lower scale values correspond to less pain on the described scale, the score has an interpretable direction for pain intensity. The registry record does not explain how participants completed the scale or how scores were collected.

The endpoint wording refers to both pain and burning sensation, but the detailed primary-outcome description specifies measurement of pain sensation by VAS. A separate numerical result for burning sensation is not reported in the registry record. Nor is a baseline pain score or a method for calculating change from baseline reported. The posted means should therefore be read as scores at the stated assessment, not assumed to be changes from an earlier measurement.

The timing is important to interpretation: these results concern the specified assessment four days after study start, not symptom experience at other times. The record does not establish whether the endpoint captures duration of relief, recurrence, or broader disease activity. It provides a limited measure of pain at a single stated follow-up point.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical quantities in this record are arm-specific means and confidence intervals for a continuous outcome. A continuous measure can take values across a scale, rather than being limited to categories such as event or no event. Here, the recorded measure is a VAS pain score, and the posted summary for each arm is its mean. A mean compresses the observed scores into a measure of their average level; it does not show the distribution of scores or how many participants had very low or high values.

What does a confidence interval describe?

In general, a confidence interval describes statistical uncertainty around an estimate, conditional on the data and the method used to calculate it. Narrower intervals usually indicate greater precision, while wider intervals indicate more uncertainty. A confidence interval for an arm mean concerns that arm's mean, not the full range of individual experiences. The registry record reports 95% confidence intervals, but does not identify the formula or assumptions used to construct them. The intervals should therefore be interpreted as posted summaries rather than as a fully reproducible analysis.

The reported mean for the arm receiving ibuprofen, diphenhydramine and Aluminium MgS is 3.176, with a 95% confidence interval of 1.169 to 5.183. The mean for the arm receiving diphenhydramine and Aluminium MgS is 3.821, with a 95% confidence interval of 2.028 to 5.614. These are separate estimates. A treatment comparison would normally focus on a contrast between arm means and quantify uncertainty in that contrast. The registry record does not report that contrast, its confidence interval, or a hypothesis-test result.

Why is a direct comparison different from comparing means?

In general, a randomized study is designed to compare outcomes between assigned groups. The relevant statistical target is usually a between-group effect, defined according to the protocol and analysis plan. Arm-specific means are useful descriptive information, but they do not by themselves show the uncertainty of the between-arm effect. The amount of uncertainty in a contrast depends on the variability and size of the groups and on the analysis used. Separate confidence intervals cannot simply be treated as a confidence interval for the contrast. No comparison estimate is reported in the registry record, and no new estimate can be recovered from the posted summaries alone without additional assumptions and data.

The record labels the outcome parameter as a mean and names 95% confidence intervals as the dispersion measure. It does not post standard deviations or other summaries of the score distribution. A confidence interval is not a measure of individual-to-individual variability. Without a reported spread measure, the reader cannot assess the degree of variation in participant scores directly from the registry entry. The entry also does not say whether the reported mean is adjusted for baseline or other variables.

What do randomization and masking contribute?

In general, random allocation can support a fair comparison by reducing systematic differences in prognostic factors between groups, on average. Double masking can reduce some forms of bias in treatment delivery, symptom reporting, and assessment, depending on who is masked and how masking is maintained. These are general methodological purposes, not confirmation of how this trial implemented the procedures. The registry record says the study was randomized and double-masked, but the randomization method, allocation concealment, masked roles, and masking assessment are not reported. It also does not describe whether treatment adherence or crossover was evaluated.

The parallel design means the record identifies two arms receiving different combinations over the study, rather than describing a crossover sequence. However, details of treatment duration and administration beyond the arm descriptions are not reported. The intervention and comparator both contain diphenhydramine and Aluminium MgS; the contrast concerns the regimen that also includes ibuprofen. Since no placebo arm is listed, the record does not provide a comparison with placebo or no treatment.

What can the sample-size information establish?

In general, sample-size planning depends on assumptions such as the effect the study aims to detect, outcome variability, significance level, allocation, and desired power. A planning illustration based on an observed effect is not the same as the trial's original design justification, and it is not observed power. The registry record does not report the trial's sample-size justification or its planned effect, variability assumptions, or target power. No such design rationale should be inferred from the completed enrollment or endpoint estimates.

The registry record gives an enrollment of 37 and outcome counts of 17 and 14. It does not explain the difference between the enrollment and the endpoint counts, or identify the analysis population represented by those counts. The reason could not be determined from the record and should not be guessed. The available information also does not establish whether all randomized participants were included in the reported means.

What is not reported about the analysis?

The registry record contains no posted analysis entries for a two-arm comparison of this continuous outcome. It does not report a test statistic, p-value, adjusted estimate, model specification, assumptions check, or approach to missing outcome data. It also does not report whether the comparison was prespecified, whether an interim analysis was planned, or how multiplicity was handled. Without these details, the arm-level summaries can be interpreted descriptively, but the inferential analysis cannot be reconstructed.

In general, continuous outcomes may be analyzed using methods that compare group means, with the choice depending on design, distribution, missingness, and any prespecified covariates. If score variability differs across groups or the distribution is unusual, those characteristics can affect the suitability of a method and the reliability of its uncertainty estimates. This is general statistical context; the registry record does not report whether such features were assessed or which method was used. No model or assumption should be attributed to this trial beyond the posted mean and confidence interval summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a secondary outcome concerning the effect of the two combinations on pain level and burning sensation, and it records two outcome measures. It does not provide a separate posted numerical result for burning sensation. A count of outcome measures does not explain how they were defined, prioritized, or included in a statistical analysis. The record does not report a multiplicity strategy, such as whether any adjustment was planned when considering more than one outcome or assessment. No family of formal statistical tests is reported.

Missing-data handling is also not described. The enrollment is 37, while endpoint results list 17 participants in the ibuprofen-containing arm and 14 in the comparator arm. The reasons these counts do not account for enrollment are not reported in the registry record. It does not state whether participants lacked a day-four assessment, were excluded for another reason, or were handled through any imputation or other missing-data method. Those explanations cannot be inferred from the counts.

The analysis population is not reported in the registry record. In particular, it does not say whether results were based on all randomized participants, participants who received treatment, or those with available outcome measurements. The study aim's use of the word intention does not specify an intention-to-treat analysis. Without an analysis-population definition and participant flow, it is difficult to determine exactly which participants the posted means represent.

The record reports no formal two-arm analysis for the continuous endpoint. It therefore offers no reported p-value or comparative confidence interval to interpret alongside the arm means. Whether analyses were adjusted, whether repeated or multiple outcomes were considered in a particular way, and whether any interim analyses occurred are not reported in the registry record. These omissions restrict assessment of the inferential plan and the possible effects of missing data or multiple outcomes on the conclusions.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

For the ibuprofen, diphenhydramine and Aluminium MgS arm, the adverse-event summary lists 17 participants at risk for serious adverse events and 17 at risk for other adverse events, with 0 affected in each category. For the diphenhydramine and Aluminium MgS arm, it lists 14 at risk for serious adverse events and 14 at risk for other adverse events, again with 0 affected in each category. These figures describe the posted event counts for the listed at-risk groups.

A reported count of 0 means that the registry entry records no affected participants in that category; it does not show that an event was impossible or that risk is absent. In general, event counts are most informative when the definitions, observation period, collection procedures, and completeness of follow-up are clear. Those details are not reported in the registry record. The entry also does not list any serious adverse-event terms.

Deaths are not reported in the registry record. They should not be interpreted as zero, because the death fields are not populated with a count. The posted adverse-event information is limited to the recorded categories and at-risk counts; it does not provide a comprehensive account of all possible harms or their timing. The figures should be read as descriptive registry reporting, not as proof of safety or a comparative safety analysis.

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

The posted results show arm-specific mean pain scores at the stated four-day assessment. The mean is 3.176 for the arm receiving ibuprofen, diphenhydramine and Aluminium MgS, with a 95% confidence interval from 1.169 to 5.183. The mean is 3.821 for the arm receiving diphenhydramine and Aluminium MgS, with a 95% confidence interval from 2.028 to 5.614. On the scale described in the registry record, lower values indicate less pain.

Those summaries describe the observed endpoint by arm. They do not establish that the added ibuprofen caused a difference in pain. The registry record does not report a direct comparison estimate, confidence interval for the difference, or p-value. It is not appropriate to infer a formal statistical conclusion from the arm means alone or from whether their separate intervals overlap.

The measurement is limited to the stated assessment time and to the endpoint as described. The registry record does not provide baseline scores or state that the posted values are changes from baseline. It also does not report a separate result for burning sensation, despite that symptom appearing in the outcome wording. No conclusion about symptom patterns at other times or other signs of RAS follows from the posted mean scores.

The design labels indicate randomized and double-masked allocation, but important implementation and analysis details are absent. The outcome counts do not account for the recorded enrollment, and the reason is not reported. The analysis population and missing-data approach are not reported either. These gaps matter because they affect how representative the endpoint summaries are and how confidently a group contrast can be interpreted.

Accordingly, the record supports a descriptive account of the reported pain scores and their arm-specific uncertainty. It does not establish the magnitude, precision, or statistical significance of a treatment effect, nor does it establish that either regimen is better or worse. Such conclusions would require a clearly reported between-arm analysis and enough information to understand the participants and methods behind it.

13. Why This Trial Matters Statistically

This trial is statistically useful as an example of the distinction between reporting group summaries and reporting a comparative effect. Randomized trials are generally intended to support comparisons between assigned arms, but the posted values are means for each arm separately. Those means tell readers about the reported pain-score level in each group; they do not quantify the uncertainty in the difference between groups. Keeping that distinction clear prevents an arm-by-arm description from being mistaken for a treatment-effect analysis.

The confidence intervals also illustrate why uncertainty should be attached to estimates. Each arm mean is accompanied by a 95% confidence interval, so the registry record communicates that the estimated mean is not exact. In general, a confidence interval is useful for considering precision, but its meaning depends on the method and assumptions used. The record does not identify the calculation method, and separate intervals do not answer the comparative question as directly as a confidence interval for the between-arm effect would.

The entry also highlights the value of transparent reporting of participant flow and analysis populations. Enrollment is listed as 37, while the endpoint counts are 17 and 14. Without an explanation, readers cannot tell why the counts differ or which participants the means represent. Reporting how missing outcomes were handled, what population was analyzed, and whether the analysis followed a prespecified plan would make the result easier to evaluate.

Finally, the trial compares two active combinations that share diphenhydramine and Aluminium MgS, with ibuprofen included in one arm. That distinction defines the scope of the randomized question: it is not a comparison with placebo or no treatment. A clear account of the contrast, endpoint, analysis, and uncertainty is essential for interpreting what the evidence can address. The registry record gives some useful descriptive information but leaves the central comparative inference unreported.

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 registry record provides limited detail about participant characteristics beyond the condition and enrollment. It does not report eligibility criteria, baseline symptom scores, age or other demographic characteristics, recruitment setting, or a participant-flow account. Without that context, readers cannot assess how closely the analyzed participants resemble a broader population with RAS or understand the composition of the endpoint groups.

The recorded enrollment is 37, whereas endpoint results list 17 participants in the ibuprofen-containing arm and 14 in the comparator arm. The reason for this mismatch is not reported in the registry record. The record does not identify the number randomized to each arm, the number completing follow-up, or whether the endpoint counts represent everyone with available measurements. This uncertainty limits interpretation of both precision and potential selection effects.

The endpoint description presents a mean VAS score at four days, but does not report baseline measurements, change-from-baseline results, or a separate numerical burning-sensation result. The score distribution and standard deviations are not posted. The registry record also does not explain the confidence-interval calculation or provide a direct between-arm estimate, test, or p-value. Consequently, the comparative effect and its precision cannot be assessed from the posted endpoint summaries alone.

Additional design and conduct details are not reported, including the randomization procedure, allocation concealment, which parties were masked, treatment adherence, and the handling of missing data. The statistical analysis plan, analysis population, sample-size justification, interim analyses, and multiplicity approach are also not reported. These omissions mean that the randomized and double-masked labels cannot be supplemented with a detailed appraisal of implementation or analysis.

The safety entry records zero affected participants in the listed serious and other adverse-event categories, but does not report the definitions, observation period, or ascertainment procedures. Death counts are not reported in the registry record. Taken together, the limitations call for a narrow reading: these are descriptive registry summaries for a specific follow-up point, with important comparative, participant-flow, and methods details unavailable.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Therapeutic Effects of "Ibuprofen, Diphenhydramine and Aluminium MgS" on Recurrent Aphthous Stomatitis — NCT01293968.
• Registry record last updated 2012-06-20; status last verified 2012-05.
• Results first posted 2012-06-20.
• 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

NCT01293968 is a completed, randomized, double-masked, parallel phase 2 trial sponsored by Qazvin University Of Medical Sciences. The registry record lists enrollment of 37 and a study start of 2010-11, with primary completion in 2011-01. The two arms were ibuprofen, diphenhydramine and Aluminium MgS, and diphenhydramine and Aluminium MgS.

The primary outcome is described as pain level and burning sensation assessed using VAS scores four days after the study began. The posted mean pain score is 3.176, with a 95% confidence interval from 1.169 to 5.183, for the ibuprofen-containing arm; the comparator mean is 3.821, with a 95% confidence interval from 2.028 to 5.614. The corresponding outcome counts are 17 and 14.

The registry record does not report a formal two-arm comparison, analysis population, missing-data method, or sample-size justification. It also does not explain the difference between enrollment and the endpoint counts. The posted results therefore describe arm-specific pain scores but do not establish a comparative treatment effect.