An Efficacy Study of Chlorhexidine Mouthwashes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy Study of Chlorhexidine Mouthwashes (NCT01751178), a randomized phase 4 study. The primary outcome is Gingival Severity Index (GSI) Based on the Gingival Index (GI).

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group, phase 4 clinical study sponsored by GlaxoSmithKline. It was listed as completed. The registry record lists enrollment of 324 and identifies gingivitis as the condition under study. The study began in 2012-10, with primary completion in 2013-03.

The study summary describes a comparison of gingival health after 6 weeks of twice-daily use of an alcohol-containing or non-alcohol mouthrinse, each used alongside brushing, against brushing only. The two mouthwash regimens specified in the record used 10ml of 0.2% w/v chlorhexidine digluconate, a timed 1-minute rinse twice daily, and brushing with standard toothpaste for a timed 1 minute. The description of the reference group’s precise regimen is not reported in the registry record.

Randomization is recorded, but the sequence-generation method, allocation concealment, and allocation ratio are not reported in the registry record. “Single” is the masking designation; the identity of the masked parties is not reported in the registry record. The trial model is parallel, meaning the listed groups are compared over the study period rather than participants being assigned to a sequence of treatments.

The primary outcome analysis population was the Intent-to-Treat population as defined in the record: participants who received study treatment and had at least one post-baseline efficacy measurement. The primary endpoint was change from baseline to 6 weeks in the Gingival Severity Index. Three secondary outcomes are also listed: Gingival Index, overall plaque scores, and interproximal plaque scores. The original sample-size rationale and the protocol’s detailed statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 775 subjects were screened and 324 subjects were randomised of whom 319 completed the study. The high screen failure rate was due mainly to subjects not having sufficient permanently gradable teeth.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis was conducted on the Intent-to-Treat (ITT) population, defined as those subjects who received study treatment and had at least one post-baseline efficacy measurement.

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 Gingival Severity Index (GSI) Based on the Gingival Index (GI), measured over Change from baseline to 6 weeks.

The primary endpoint is the change from baseline to 6 weeks in the Gingival Severity Index (GSI), based on the Gingival Index (GI). The record describes GSI as a measure of gingival severity averaged across whole-mouth sites. It states that sites are scored on the GI scale and gives categories related to bleeding: GSI equals 0 when GI is 0 or 1, described as no bleeding, and GSI equals 1 when GI is 1 or 2, described as bleeding. Because GI value 1 appears in both descriptions, the exact categorization at that value is ambiguous in the registry record.

A change score is intended to describe how the measure differs from baseline at the specified follow-up, rather than simply reporting a single follow-up reading. The whole-mouth average provides a summary across sites, while retaining a continuous mean for group comparisons. The registry reports means with standard errors for the primary outcome and identifies the analysis population as participants who received study treatment and had at least one post-baseline efficacy measurement.

Using a defined clinical index makes it possible to compare the recorded group-level changes statistically. The index’s scale and interpretation matter: the record supplies units as “Units on a scale,” but does not report a minimum clinically important difference or explain what magnitude of mean change would be important to participants or clinicians. Statistical evidence about a group contrast therefore does not, by itself, establish the practical importance of that contrast.

7. Results Posted in the Registry

• Mouthwash With Alcohol: mean 0.15 versus 0.21 on control; difference -0.06 (95% CI -0.09 to -0.03), standardized effect d = -0.56; z-test p = <0.001.
• Mouthwash Without Alcohol: mean 0.14 versus 0.21 on control; difference -0.07 (95% CI -0.10 to -0.04), standardized effect d = -0.68; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Gingival Index

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Mouthwash With Alcohol: mean 1.12 versus 1.19 on control; difference -0.07 (95% CI -0.11 to -0.03), standardized effect d = -0.52; z-test p = <0.001.
  • Mouthwash Without Alcohol: mean 1.11 versus 1.19 on control; difference -0.08 (95% CI -0.11 to -0.05), standardized effect d = -0.64; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mouthwash With Alcohol than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mouthwash Without Alcohol than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Turesky Modification of Quigley & Hein Plaque Index for Overall Plaque Scores

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Mouthwash With Alcohol: mean 2.50 versus 3.34 on control; difference -0.84 (95% CI -1.04 to -0.64), standardized effect d = -1.13; z-test p = <0.001.
  • Mouthwash Without Alcohol: mean 2.40 versus 3.34 on control; difference -0.94 (95% CI -1.14 to -0.74), standardized effect d = -1.22; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mouthwash With Alcohol than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mouthwash Without Alcohol than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Turesky Modification of Quigley & Hein Plaque Index for Interproximal Plaque Scores

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Mouthwash With Alcohol: mean 2.77 versus 3.69 on control; difference -0.92 (95% CI -1.14 to -0.70), standardized effect d = -1.14; z-test p = <0.001.
  • Mouthwash Without Alcohol: mean 2.63 versus 3.69 on control; difference -1.06 (95% CI -1.28 to -0.84), standardized effect d = -1.29; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mouthwash With Alcohol than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mouthwash Without Alcohol than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover Gingival Index and plaque scores measured overall and at interproximal sites. Across the posted mean summaries and simple comparisons with the reference group, the pattern is generally in the same direction as the primary endpoint: the mouthwash-group means are lower than the reference-group means for these measures. The sponsor’s adjusted results also generally report negative contrasts. This broad consistency provides context for the primary result, but the secondary measures are related outcomes rather than independent confirmation of a single primary claim.

There is a reporting detail that limits direct comparison across all secondary analyses. For the interproximal plaque outcome, the posted sponsor analysis lists the comparison between the alcohol and non-alcohol mouthwash groups, whereas the unadjusted comparisons are presented against the reference group. These contrasts answer different questions. The registry record does not explain the choice of comparison or provide enough detail to reconcile the two reporting frames.

Secondary outcomes typically carry less weight than a prespecified primary endpoint because they may be exploratory and because testing many outcomes or contrasts increases the chance of finding apparently strong results by chance. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting the secondary outcomes. Their p-values should therefore be read as individual results rather than as a family-wise conclusion.

The secondary outcomes do not establish whether the observed differences are important in practice. The record does not report clinical-importance thresholds for these scales. Nor does it provide a complete analysis plan describing the role of each secondary measure. The overall pattern is useful as supporting context, but it cannot replace the primary analysis or resolve the reporting and multiplicity uncertainties.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Gingival Index
• Turesky Modification of Quigley & Hein Plaque Index for Overall Plaque Scores
• Turesky Modification of Quigley & Hein Plaque Index for Interproximal Plaque Scores

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary results include a sponsor-reported ANCOVA analysis and unadjusted comparisons recalculated from summary statistics. These approaches answer related but not identical questions. The ANCOVA is the registry’s reported analysis; the recalculation uses the posted group summaries without adjustment. A close numerical resemblance between them does not make the methods interchangeable.

What does ANCOVA do?

ANCOVA, or analysis of covariance, estimates a group contrast while accounting for one or more covariates. In clinical trials, adjustment can account for baseline measurements or other prespecified variables, potentially improving precision when those variables are associated with the outcome. The registry names ANCOVA for the sponsor’s analyses but does not report the full model specification, the covariates included, or the assumptions and diagnostics used. Those details are therefore not reported in the registry record.

The adjusted mean difference is an estimate of the modeled average contrast between a mouthwash group and the reference group. Its confidence interval describes uncertainty under the fitted model and its assumptions. Adjustment does not automatically eliminate bias, correct missing data, or make a result clinically important. The interpretation depends on the model and the underlying trial conduct.

What is an unadjusted recalculation?

The recalculated mean differences are simple comparisons of posted group summaries. They do not reproduce an ANCOVA model because the summary information does not include the participant-level covariates and model details needed to do so. The recalculated interval and p-value are consequently best viewed as an independent, unadjusted statistical check of the posted means, not as a substitute for the sponsor’s analysis.

The mean difference is expressed in the outcome’s scale units. A negative estimate follows the comparison direction used in the posted results: mouthwash group relative to reference. It means the mouthwash group mean is lower in the reported contrast. The estimate does not convey the full distribution of participant outcomes, and it does not show whether effects vary across participants or sites.

How should a confidence interval be understood?

In general, a confidence interval is a range of estimates compatible with the observed data and the procedure’s assumptions. It conveys both the direction and precision of an estimated contrast. It is not a range containing a known fixed proportion of individual participant outcomes, and it is not a probability statement that the true value lies inside a particular interval. A narrow interval indicates greater statistical precision than a wide interval, while the interval’s position relative to zero helps describe evidence for a nonzero contrast.

For the sponsor-reported primary analyses, each 95% confidence interval lies below zero. The interval for mouthwash with alcohol extends from -0.081 to -0.041; for mouthwash without alcohol it extends from -0.090 to -0.050. These intervals quantify uncertainty around the adjusted group contrasts. They do not include uncertainty about unreported design choices, missing-data handling, or the validity of the outcome definition.

What do the p-values say?

A p-value describes how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions are correct. It is not the probability that the null hypothesis is true, nor does it measure effect size or clinical importance. The sponsor reports p < 0.001 for each primary ANCOVA comparison; the unadjusted recalculations report p < 0.001. These results indicate strong evidence against a zero contrast under their respective analyses. The record does not report whether the p-values account for testing multiple outcomes or comparisons.

Why do standard errors matter?

A standard error describes the estimated sampling uncertainty of a statistic, such as a mean. It is different from a standard deviation, which describes variation among individual observations. The arm-level primary summaries report standard errors of 0.009, 0.007, and 0.012 for the alcohol, non-alcohol, and reference groups. Smaller standard errors generally indicate more precise estimates of the means, but should be interpreted with the sample sizes, outcome scale, and analysis method in mind.

General statistical principle: when outcomes vary more than a model assumes, uncertainty can be understated and tests can appear more conclusive than they should. That issue is often discussed as over-dispersion for count or categorical data. The primary endpoint is reported as a continuous mean, and the registry does not report an over-dispersion assessment or relevant diagnostic results. It is not possible to infer those diagnostics from the summary values alone.

What cannot be reconstructed?

The registry record does not report the original sample-size justification, the full statistical analysis plan, covariate list, model diagnostics, interim analyses, missing-data method, or multiplicity procedure. These omissions limit independent assessment of whether the reported analyses followed a prespecified plan and how robust the results are to alternative assumptions. The posted summaries support descriptive and unadjusted checks, but cannot recreate participant-level analyses or evaluate the trial’s full modeling choices.

11. Confidence Intervals and Precision

Precision is conveyed by the width and location of the confidence intervals around the estimated group contrasts. For the primary adjusted analysis, the mouthwash-with-alcohol contrast is -0.061, with a 95% confidence interval from -0.081 to -0.041. The mouthwash-without-alcohol contrast is -0.070, with a 95% confidence interval from -0.090 to -0.050. In both cases, the intervals remain below zero, so the reported adjusted estimates are directionally consistent across the interval.

The intervals do not establish how important the estimated differences are in practice. The registry record does not report a threshold for a clinically important GSI change, nor does it provide a direct interpretation of a particular number of scale units. Statistical precision and clinical relevance are separate questions: an estimate can be reasonably precise without the record establishing that its magnitude matters to patients.

The unadjusted recalculated intervals are wider than the sponsor-reported adjusted intervals: -0.089 to -0.031 for mouthwash with alcohol and -0.097 to -0.041 for mouthwash without alcohol. This comparison reflects different analysis approaches, not a direct competition between identical estimates. ANCOVA may gain precision through adjustment, but the model specification and covariates are not reported in the registry record, so the source of the precision difference cannot be fully assessed.

Confidence intervals also do not capture every uncertainty relevant to interpretation. They rely on the analysis and data assumptions, while uncertainty about missingness, multiple testing, and the measure’s definition requires additional information. The primary endpoint description’s overlap at GI value 1 is another interpretive limitation not represented in the statistical intervals.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants or total events. They are illustrative calculations based on the observed effect, rather than the trial’s own original design calculations. The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; each scenario uses the stated fraction of the observed effect as the effect to detect. The trial’s original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the calculated participants per arm for a design with 80% power under those assumptions. In plain terms, power is the probability of detecting an effect of the specified size if that effect is real, under the statistical model and assumptions used. The 90% power column gives the corresponding planning count for a higher target probability of detection. Neither column describes the probability that the trial’s result is true.

Rows planning for 100%, 75%, and 50% of the observed effect illustrate how the assumed effect size changes the required sample size. Smaller effects are harder to distinguish from random variation, so the planning calculation calls for more participants per arm to detect them at the same target power. The figures are not observed power: they are hypothetical planning illustrations based on selected assumptions, not a retrospective measure of what the completed study achieved.

A sample-size curve should be read as a display of how the calculated requirement changes with the effect-size assumption. It does not validate the trial design or show what sample size the investigators originally intended. The registry record does not report whether the trial’s enrollment target was based on this endpoint, another endpoint, or a different set of assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.060; pooled standard deviation σ = 0.107.
2. n = 2 × (1.96 + 0.842)² × 0.107² / -0.060² = 50.1, rounded up to 51 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.06                      # observed difference in means
sigma <- 0.107143128571085                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1751178)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 51 (80% power), 68 (90% power)
 75% of observed effect: n per arm = 89 (80% power), 120 (90% power)
 50% of observed effect: n per arm = 201 (80% power), 269 (90% power)
power.t.test: 51 
Simulated power at n = 51 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports ANCOVA estimates for the primary endpoint: an adjusted mean difference of -0.061 for mouthwash with alcohol versus reference and -0.070 for mouthwash without alcohol versus reference. Each has a reported 95% confidence interval and p < 0.001. The simple unadjusted recalculations from the posted summaries are -0.06 and -0.069, with p < 0.001 for each. The estimates are close in direction and magnitude, but the recalculations do not reproduce the adjusted model.

The registry does not flag a discrepancy between the posted values and the recalculated results. The sponsor’s own analysis therefore remains the relevant reported analysis, while the recalculation serves as a summary-statistic check. Differences in estimates and intervals are expected when an adjusted model is compared with an unadjusted calculation. The full ANCOVA specification, including covariates and diagnostics, is not reported in the registry record, so the adjusted results cannot be independently reconstructed from these summaries.

The sponsor’s p-values should be interpreted within the stated comparisons and the analysis method. The record does not report whether these tests were adjusted for multiple comparisons. That issue matters when interpreting a set of endpoints and treatment contrasts together, but does not change what the individual reported ANCOVA estimates are.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and three secondary outcomes, with multiple treatment comparisons and analyses. When many hypotheses are tested, the chance of at least one small p-value can increase even if no true effects exist. Statistical procedures can address this by controlling an error rate across a defined family of tests, or by specifying a hierarchy that determines which results are confirmatory. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which outcomes were intended to support confirmatory conclusions.

The reported p-values are therefore best interpreted as results for their individual comparisons. A small p-value for one endpoint does not account for the number of other endpoints or contrasts that may have been examined. This caution is especially relevant for secondary outcomes, for which the record does not state whether they were exploratory or confirmatory.

The primary analysis population is defined as participants who received study treatment and had at least one post-baseline efficacy measurement. This definition gives a clear rule for inclusion in that analysis, but it is not the same as including every randomized participant regardless of post-baseline data. The registry record does not report the number of randomized participants by group, the number excluded from the primary analysis, or the reasons for missing outcome measurements.

How missing data were handled, whether any imputation was used, and whether sensitivity analyses assessed departures from the main assumptions are not reported in the registry record. Missingness can affect interpretation if the availability of measurements is related to outcomes or treatment. Without those details, it is not possible to assess the robustness of the results to alternative missing-data assumptions.

The record also does not report interim analyses or the full prespecified statistical analysis plan. These omissions do not invalidate the posted estimates, but they restrict assessment of selective analysis choices and the intended control of false-positive findings.

16. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cellulitis left thigh (0.9%).

The serious-adverse-event summary reports 0 participants with a serious event among 108 at risk in the mouthwash-with-alcohol group, 1 among 109 at risk in the mouthwash-without-alcohol group, and 0 among 107 at risk in the reference group. The registry lists “Cellulitis left thigh” at 0.9% among the serious-event terms. These are counts and a listed term, not evidence on their own about whether an event was caused by a study treatment.

The record also reports other adverse events for 67 of 108 at risk in the alcohol group, 60 of 109 in the non-alcohol group, and 47 of 107 in the reference group. The registry does not provide enough detail in these summaries to assess event severity, timing, duration, or treatment relationship. Death counts are not reported in the registry record.

These figures are descriptive safety reporting within the recorded groups. Small numbers of serious events provide limited information about uncommon harms, and the record does not report a formal comparative safety analysis. The event counts should not be interpreted as proof that an event was or was not caused by an intervention.

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

The posted results show lower mean values for the two mouthwash groups than for the reference group on the primary GSI measure, with negative adjusted mean differences and 95% confidence intervals below zero. The sponsor reports p < 0.001 for both primary comparisons. The simple unadjusted recalculations point in the same direction. These statements describe group-level results for the defined analysis population over the specified 6-week timeframe.

They do not establish that every participant experienced a change in the same direction, or that an individual participant would have the group-average response. Mean differences summarize groups and do not show the full spread or distribution of individual outcomes. The record also does not define a clinically important difference on the GSI scale, so statistical evidence alone cannot determine the practical importance of the estimated contrasts.

The comparisons do not establish the effect of mouthwash in every setting or over periods beyond the study’s 6-week assessment. The registry does not report longer-term outcomes. Although the summary describes a brushing-only comparison, the reference regimen’s full details are not reported in the registry record. That limits the precision with which the comparator can be characterized.

The secondary outcomes generally show a similar direction in their posted mean comparisons, but they involve multiple measures and the registry does not report a multiplicity strategy. In addition, the interproximal plaque sponsor comparison is listed between the two mouthwash groups rather than against the reference group. These details call for restraint when treating secondary results as confirmatory.

The results are not medical advice and do not determine what an individual should use. They report statistical comparisons in this trial; interpretation depends on the outcome definition, model assumptions, missing-data methods, multiplicity, and clinical context, several of which are not reported in the registry record.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation requires more than reading a p-value. The registry provides both adjusted ANCOVA results and enough group-level information for simple unadjusted recalculations. The two approaches yield similar directions and broadly similar estimates, while their different adjustment strategies produce differences in the exact estimates and interval widths. Distinguishing an adjusted model result from a summary-statistic recalculation is essential for transparent interpretation.

It also shows the value of reporting confidence intervals alongside tests. The adjusted intervals quantify uncertainty around the estimated primary contrasts and locate those estimates relative to zero. They make the direction and precision easier to judge than p-values alone, while leaving clinical importance as a separate question that requires a meaningful scale threshold.

The design and reporting details demonstrate why analysis populations and missing-data methods matter. The primary analysis requires treatment receipt and at least one post-baseline efficacy measurement; the record does not describe the missingness pattern or how unavailable measurements were handled. Likewise, the endpoint and secondary results involve several comparisons, yet the multiplicity approach is not reported. These are important elements of a full evidence assessment, not technical details that can be inferred from a small p-value.

Finally, the record shows how consistent directions across related endpoints can inform context without replacing a primary result. Secondary outcomes add perspective, but their evidential weight depends on prespecification, multiplicity, and coherent comparison definitions. Clear reporting of those features would make the results easier to evaluate and reproduce.

19. 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 limitations affect interpretation. First, the GSI definition in the registry record appears to assign GI value 1 to both the no-bleeding and bleeding categories. The record does not clarify this overlap, so the exact scoring rule at that value is uncertain. The reported numerical results can be described, but the scale’s clinical interpretation is less clear without resolution of the definition.

Second, although the study summary describes comparison with brushing only, the reference arm’s regimen is not specified in the arm descriptions. This limits the ability to describe the practical contrast fully. The masking designation is single, but the party or parties masked are not reported in the registry record. Details of randomization and allocation concealment are also not reported.

Third, the registry does not report the original sample-size justification, the complete statistical analysis plan, ANCOVA covariates, model diagnostics, interim analyses, or the approach to missing outcome data. The primary analysis population includes participants with at least one post-baseline measurement, and the record does not state how many randomized participants lacked such measurements or why.

Fourth, multiplicity procedures and clinical-importance thresholds are not reported. The secondary results include multiple measures and comparisons, and the interproximal plaque sponsor analysis lists a mouthwash-to-mouthwash comparison rather than the reference comparison used in the unadjusted summaries. These reporting differences complicate a unified interpretation of secondary findings.

Finally, follow-up for the primary outcome is at 6 weeks. Longer-term outcomes are not reported in the registry record. The available safety summaries are descriptive and do not provide a formal comparative analysis or enough detail to establish event causality.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: An Efficacy Study of Chlorhexidine Mouthwashes — NCT01751178.
• Registry record last updated 2014-07-28; status last verified 2014-06.
• Results first posted 2014-07-28.
• 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.

23. Record Summary

This completed, randomized, single-masked, parallel-group phase 4 study enrolled 324 participants with gingivitis. It compared alcohol-containing and alcohol-free chlorhexidine mouthwash regimens, used with brushing, with a reference group described in the study summary as brushing only. The primary endpoint was change from baseline to 6 weeks in the Gingival Severity Index.

The sponsor-reported ANCOVA results give adjusted mean differences of -0.061 for mouthwash with alcohol and -0.070 for mouthwash without alcohol versus reference; both reported p-values are < 0.001. Unadjusted recalculations from the posted summaries are similar in direction. Three secondary outcomes are listed, with generally similar directions in the posted summaries, though multiplicity and one comparison-frame detail warrant caution.

The registry record does not report the original sample-size justification, missing-data method, multiplicity procedure, clinical-importance threshold, or full ANCOVA specification. Safety summaries report one serious adverse event in the non-alcohol group and none in the other listed groups.