Effect of Irrigation-Activation Techniques on Healing in Large Periapical Lesions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Irrigation-Activation Techniques on Healing in Large Periapical Lesions (NCT06204887), a randomized na study. The primary outcome is Percentage Change in Lesion Volume at 12-months Follow-up.

2. Clinical Question

The statistical question is about a measured imaging outcome, rather than a direct measure of symptoms or another clinical endpoint. The registry record does not report a separate primary comparison between each activation method and the control, nor does it specify a clinically important threshold for percentage change. Consequently, the reported group-level test and the unadjusted pairwise recalculations address related but distinct questions: whether the four groups differ overall, and how each activation group’s mean compares with the control mean.

3. Trial Design

The registry describes a completed, randomized, single-masked, parallel-group trial with four groups: manual dynamic activation, passive ultrasonic activation, laser activation, and a non-activated control. The recorded enrollment is 97. The posted primary-outcome summaries list n=14 for each group. The record does not explain the relationship between the enrollment figure and the number of observations in those outcome summaries, or state how many participants contributed data at the 12-month assessment.

The study began on 2021-11-01 and had a primary completion date of 2023-02-27. Its stated focus was healing of large periapical lesions after different irrigation-activation treatments. The summary describes CBCT-based volumetric change analysis during 1-year follow-up. The primary outcome was percentage change in lesion volume at 12 months, expressed as a mean and standard deviation for each group.

Random allocation and a parallel design mean that participants were assigned to one of the listed groups, which were compared over the study period. The registry reports single masking but does not identify who was masked. It does not report further information about the randomization procedure, allocation concealment, treatment adherence, or whether the imaging assessment was masked.

The registry lists the phase as NA and the status as completed. It names Recep Tayyip Erdogan University as sponsor. Detailed eligibility criteria, the planned original sample size, the rationale for the enrollment target, and the full protocol are not reported in the registry record. The reported outcome results are based on group summaries; the record does not state the analysis population used or describe participant flow through follow-up.

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: Of 97 enrolled participants, 70 met inclusion criteria and randomized to irrrigation protocols.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage Change in Lesion Volume at 12-months Follow-up, measured over One year from the beginning of the study.

The primary endpoint is percentage change in lesion volume at 12-month follow-up. Lesion volume was measured from CBCT images taken before treatment and at the end of 1 year. The record describes segmenting the images in 0.09 mm intervals, defining lesion borders by grayscale, and using software to fill the outlined volume. It notes that manual correction could be made during measurement before the software calculated defect volume in mm3. The resulting volume data were compared with pre-operative CBCT measurements, and percentage volume change was used to assess changes in periapical tissues over time.

Volumetric measurement provides a quantified imaging outcome for comparing change in lesion size across treatment groups. A three-dimensional measure can represent the extent of a lesion rather than relying only on a single linear dimension. For statistical interpretation, however, the endpoint remains a measurement of percentage change: the posted record does not define a threshold for a clinically important difference, or give a separate measure of patient experience.

The registry reports group means and standard deviations for the endpoint at 12 months. It does not state how the percentage-change calculation was defined in detail, how missing or unusable scans were handled, or whether the measurement process was assessed for reproducibility. Those details are relevant when interpreting an imaging outcome, because measurement and analysis choices can affect the resulting estimates.

7. Results Posted in the Registry

• Manual dynamic activation: mean 80.43 versus 74.57 on control; difference 5.86 (95% CI -18.34 to 30.06), standardized effect d = 0.18; z-test p = 0.635.
• Passive ultrasonic activation: mean 85.43 versus 74.57 on control; difference 10.86 (95% CI -8.80 to 30.51), standardized effect d = 0.41; z-test p = 0.279.
• Laser activation: mean 86.93 versus 74.57 on control; difference 12.36 (95% CI -10.34 to 35.06), standardized effect d = 0.40; z-test p = 0.286.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the Kruskal–Wallis result test?

The registry reports a Kruskal–Wallis analysis across the four groups, with p < 0.05. In general, the Kruskal–Wallis test is a rank-based method for comparing outcome distributions across independent groups. It ranks observations rather than relying directly on a comparison of group means. A statistically significant overall result indicates evidence that the groups’ outcome distributions are not all the same under the test’s assumptions. It does not, by itself, identify which groups account for that evidence.

The registry record does not report a test statistic, degrees of freedom, group-specific ranks, or follow-up pairwise tests. It also does not report whether the analysis was planned in advance or how any follow-up comparisons were adjusted. As a result, the reported p-value is evidence for an overall difference, but it cannot be used to infer a particular pairwise contrast or the size of a difference.

What do the mean differences represent?

The posted group summaries also permit simple unadjusted recalculations of the mean difference between each activation group and the non-activated control. The recalculated estimates are 5.858 for manual dynamic activation, 10.86 for passive ultrasonic activation, and 12.36 for laser activation. In each comparison, the estimate is the activation-group mean minus the control-group mean on the reported percentage-change scale. A positive estimate therefore means that the activation group’s posted mean is numerically higher on that scale; the record does not provide a clinically meaningful threshold for interpreting the magnitude.

These pairwise calculations use the posted group means and standard deviations, rather than participant-level data or an adjusted model. They are not the same as the sponsor’s Kruskal–Wallis test. In general, a difference in means describes a contrast in group averages, while a rank-based test assesses distributions using the ordering of observations. When distributions have different shapes or spreads, the two methods can answer meaningfully different questions.

Why is variability important?

The standard deviations indicate how dispersed individual outcome values were around each group mean. The reported standard deviations vary across groups: 28.29 for manual dynamic activation, 8.635 for passive ultrasonic activation, 23.33 for laser activation, and 36.52 for the non-activated control. In general, greater within-group variability makes a group mean less precise when the number of observations is fixed. Unequal variability can also affect how well methods based on common-variance assumptions describe the data. The record does not report diagnostics or participant-level distributions, so the effect of the observed spread on the sponsor’s analysis cannot be evaluated in detail.

Over-dispersion is a general concern when variability is larger than a model assumes: standard errors may be understated, and uncertainty can appear narrower than it is. The record does not identify a model that assumes a particular variance structure, so over-dispersion should not be asserted as a demonstrated problem in this trial. The wide spread in some group summaries nevertheless makes it important to consider variability alongside the means.

How should the confidence intervals and p-values be read?

A confidence interval gives a range of values reasonably compatible with the data under the calculation method. In general, a 95% confidence interval describes the uncertainty of an estimate and should not be read as a range containing 95% of individual participants’ outcomes. The recalculated intervals for all three mean differences include zero. They therefore do not exclude a zero mean difference at the corresponding unadjusted level, but they also include differences in either direction. They are not evidence of equivalence, which would require an appropriate margin and analysis not reported in the registry.

A p-value describes how unusual data at least as inconsistent with a specified null hypothesis would be if that null hypothesis and the analysis assumptions held. It does not give the probability that the null hypothesis is true, or measure clinical importance. The recalculated p-values are unadjusted pairwise results. The registry’s reported p < 0.05 is from an overall test and should not be substituted for those pairwise p-values.

What cannot be established from these summaries?

Summary statistics do not show the individual outcome distribution, possible outliers, or whether observations were missing in a way related to outcome. The registry record does not report participant-level data, the analysis population, imputation or other missing-data procedures, or sensitivity analyses. Nor does it provide enough detail to reproduce the sponsor’s Kruskal–Wallis analysis. Those omissions limit independent assessment of model assumptions, robustness, and the relationship between the overall test and pairwise results.

10. Confidence Intervals and Precision

The recalculated mean differences are 5.858 for manual dynamic activation versus the non-activated control, 10.86 for passive ultrasonic activation versus control, and 12.36 for laser activation versus control. Their 95% confidence intervals are, respectively, -18.34 to 30.06, -8.797 to 30.51, and -10.34 to 35.06. All three intervals include zero. Thus, each unadjusted estimate is compatible with no mean difference as well as with differences on either side of zero.

The intervals are broad relative to their point estimates. This means the summary data do not determine the size or direction of each pairwise mean contrast precisely. A point estimate alone can be misleading when its uncertainty includes a substantial range of possibilities. Conversely, the intervals do not establish that there is no difference: failure to exclude zero is not proof that groups are equivalent. The registry does not report a clinically meaningful margin against which to judge equivalence or importance.

The sponsor-reported overall Kruskal–Wallis p < 0.05 is a separate result. It indicates an overall group-level finding but does not supply a confidence interval for a particular contrast. The recalculated intervals are unadjusted pairwise comparisons of means and should not be treated as intervals from the sponsor’s analysis. The record does not report sponsor-generated pairwise intervals or multiplicity adjustments.

Precision is also limited by the scope of the posted summaries. Each outcome group is reported with n=14, but the registry does not explain how those observations relate to the enrollment of 97 or clarify the number with complete 12-month imaging. Without participant flow, missing-data information, or the sponsor’s detailed analysis, the extent to which the posted estimates represent the randomized groups cannot be fully assessed.

11. 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 event counts. They are illustrations based on the observed pairwise effects, not the original trial’s design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each comparison, the effect to detect is set to the stated fraction of the observed effect.

The 80% power column gives the approximate number of participants per arm for a planning scenario designed to have an 80% chance of detecting the specified effect if that effect and the calculation assumptions were correct. The 90% power column gives the corresponding number per arm for a 90% chance. These are planning concepts, not guarantees about the result of a future study. The original trial’s sample-size justification and design assumptions are not reported in the registry record.

The rows describe planning for 100%, 75%, or 50% of the observed effect. For manual dynamic activation versus control, planning for 100% of the observed effect gives 489 participants per arm for 80% power and 654 for 90% power; planning for 75% gives 868 and 1,162; planning for 50% gives 1,953 and 2,614. For passive ultrasonic activation versus control, the corresponding pairs are 94 and 126, 167 and 224, and 375 and 502. For laser activation versus control, they are 97 and 130, 172 and 230, and 387 and 517.

Smaller effects require more participants under these assumptions, which is why the planning numbers rise as the assumed effect falls from the observed estimate. These calculations are not observed power. They do not establish whether the completed trial was adequately powered, and they do not override the uncertainty in the posted estimates or the sponsor’s reported analysis.

12. 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 = 5.858; pooled standard deviation σ = 32.664.
2. n = 2 × (1.96 + 0.842)² × 32.664² / 5.858² = 488.1, rounded up to 489 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 <- 5.858                      # observed difference in means
sigma <- 32.6641673780306                     # 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(6204887)
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 = 489 (80% power), 654 (90% power)
 75% of observed effect: n per arm = 868 (80% power), 1,162 (90% power)
 50% of observed effect: n per arm = 1,953 (80% power), 2,614 (90% power)
power.t.test: 489 
Simulated power at n = 489 per arm: 0.798 (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.

13. Analyses Reported by the Sponsor

The registry’s reported analysis is a Kruskal–Wallis test across the four groups, with p < 0.05. That is the sponsor’s own reported group-level analysis. The recalculated results compare each activation group’s mean with the control mean using posted summary statistics. They are unadjusted pairwise re-calculations and are not a replication of the rank-based overall test.

The recalculated mean differences are 5.858 for manual dynamic activation, 10.86 for passive ultrasonic activation, and 12.36 for laser activation. Their 95% confidence intervals all include zero, and their unadjusted p-values are 0.635, 0.279, and 0.286, respectively. The discrepancy between the overall reported result and these pairwise recalculations is flagged in the registry record. The sponsor’s own analysis takes precedence.

The two findings need not answer the same statistical question. An overall rank-based test asks whether the groups’ distributions differ somewhere across the set of groups. The recalculations ask about specific differences in means against the control. A significant overall result does not imply that each pairwise mean contrast is significant. The registry does not provide the sponsor’s detailed output, pairwise follow-up tests, or explanation for the discrepancy, so no more specific reconciliation can be made from the record.

14. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary endpoint and a four-group Kruskal–Wallis analysis. It does not report a multiplicity strategy for follow-up comparisons, identify planned contrasts, or state whether the overall test was the only confirmatory analysis. Multiple comparisons can increase the chance of at least one false-positive finding when many hypotheses are tested. In general, adjustments or a prespecified hierarchy can address that issue, but the record does not say whether either approach was used. The unadjusted pairwise recalculations should therefore be interpreted as exploratory contrasts, not as multiplicity-controlled sponsor results.

The registry record does not report missing-data counts, reasons for missingness, how incomplete CBCT measurements were handled, or whether any imputation was performed. It also does not describe a sensitivity analysis for missing outcomes. The outcome summaries list n=14 in each group, while recorded enrollment is 97; the registry does not explain this difference. It is not possible from the posted information to determine whether all randomized participants were included in the primary analysis or why some participants may not appear in the summaries.

The analysis population is not reported in the registry record. In particular, the record does not state whether the primary analysis followed intention-to-treat principles, included only participants with complete imaging, or used another population definition. The randomization method and allocation concealment are also not described in the available record, and the identity of the masked party is not specified. These details matter for judging potential bias and for understanding how closely the reported analysis preserves the randomized comparison.

No secondary outcome results are posted. The registry lists two outcome measures but gives no secondary results in the posted outcomes. Without a fuller protocol or statistical analysis plan, the planned outcome hierarchy, handling of protocol deviations, and any interim analyses are not reported in the registry record. The absence of these details limits evaluation of selective reporting and the confirmatory status of the reported analysis; it does not establish that such practices occurred.

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

The registry reports evidence of an overall difference among the four groups on the primary lesion-volume outcome using a Kruskal–Wallis test, with p < 0.05. The posted group means are 80.43 for manual dynamic activation, 85.43 for passive ultrasonic activation, 86.93 for laser activation, and 74.57 for non-activated control. These are descriptive averages on the reported percentage-change scale. The record does not supply a clinically important threshold or enough detail to determine the practical meaning of a particular difference.

The overall test does not establish which group differed from which. The recalculated pairwise comparisons with the control have confidence intervals that include zero and unadjusted p-values above 0.05. Those recalculations are not the sponsor’s reported analysis, and the flagged discrepancy means the sponsor’s analysis takes precedence. Neither result should be stretched into a claim that a specific technique is superior to control or that the groups are equivalent.

The endpoint is based on CBCT-derived lesion volume at the start of treatment and at 12 months. It captures an imaging measure over the stated follow-up period, not every dimension of healing or patient experience. The registry does not report a separate symptom outcome, a longer-term outcome, or a threshold linking a percentage change to a clinical benefit.

The results also have reporting limits. The record does not explain the relationship between enrollment of 97 and n=14 in each posted group summary, nor does it specify the analysis population or missing-data handling. It does not identify who was masked or provide detailed pairwise output from the sponsor’s analysis. Accordingly, the most defensible reading is limited to the recorded overall statistical finding, the observed group summaries, and the uncertainty surrounding the separate unadjusted recalculations. These results alone do not establish a treatment recommendation or a definitive clinical conclusion.

16. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between an overall test and pairwise comparisons. The sponsor-reported Kruskal–Wallis result addresses whether the four groups differ overall, whereas the recalculated mean differences address each activation group relative to the control. Those analyses can yield different conclusions without being direct contradictions, because they use different summaries and test different hypotheses.

The example also shows why effect estimates and uncertainty should accompany significance testing. The group means vary, but the pairwise recalculated confidence intervals are broad and include zero. The overall p-value alone does not describe the size, direction, or precision of a specific contrast. Nor does a non-significant pairwise recalculation prove there is no difference. Reading the results requires keeping the statistical question, estimate, and uncertainty together.

Another important issue is the relationship between the randomized enrollment and the outcome summaries. The registry records enrollment of 97 but lists n=14 in each group for the primary measure. The record does not explain the difference, making participant flow and analysis-population information especially relevant. Transparent reporting of missing imaging, analysis choices, and pairwise procedures would help readers assess how robustly the findings represent the randomized comparisons.

Finally, the sample-size illustrations demonstrate how planning depends on the effect assumed: smaller target effects require more participants under the stated assumptions. These illustrations are not the original design rationale and are not observed power. They are useful for understanding the scale of a future planning exercise, while leaving the trial’s original justification unreported.

17. 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 posted record leaves important design and reporting details unresolved. It does not describe eligibility criteria, participant characteristics, the randomization procedure, allocation concealment, or who was masked. Arm descriptions are blank, so the detailed procedures and control condition cannot be assessed from those descriptions. The summary mentions SWEEPS, while the intervention and arm labels identify laser activation; the record does not clarify that terminology.

There is an unexplained difference between recorded enrollment of 97 and n=14 in each primary-outcome group summary. The record does not report participant flow, the number with usable baseline and follow-up scans, reasons for missing measurements, or the analysis population. This limits assessment of attrition and the completeness of the 12-month comparison. It also does not report whether image assessments were reproducible or whether assessors were masked.

The statistical reporting is incomplete for independent interpretation. The sponsor’s Kruskal–Wallis result is given only as p < 0.05; the test statistic and additional analysis details are not reported. The record does not describe prespecified pairwise tests, multiplicity control, missing-data methods, sensitivity analyses, or the original sample-size justification. The recalculated comparisons use posted summary statistics and are unadjusted; they cannot resolve the discrepancy with the sponsor’s overall analysis.

Adverse-event entries list zero participants at risk and zero events in each group. Because the record lists no participants at risk for those entries, these values do not provide an informative assessment of adverse events. The registry also posts no secondary outcome results. These limitations describe gaps in the registry record and do not establish that the corresponding procedures or analyses were absent from the full study materials.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Effect of Irrigation-Activation Techniques on Healing in Large Periapical Lesions — NCT06204887.
• Registry record last updated 2025-12-24; status last verified 2025-12.
• Results first posted 2025-05-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The registry describes a completed randomized, single-masked, parallel-group trial of manual dynamic activation, passive ultrasonic activation, laser activation, and a non-activated control for large periapical lesions. Recorded enrollment is 97. The primary outcome is percentage change in lesion volume at 12-month follow-up, assessed using CBCT measurements. The posted group summaries report n=14 for each group.

The sponsor reports a Kruskal–Wallis group-level analysis with p < 0.05. Separate unadjusted recalculations of each activation group versus control have confidence intervals that include zero; because the registry flags a discrepancy, the sponsor’s own analysis takes precedence. The record does not report the original sample-size rationale, analysis population, missing-data methods, multiplicity procedures, or detailed pairwise results.