This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Buffered vs. Unbuffered Local Anesthesia in Mandibular Molars Diagnosed With Symptomatic Irreversible Pulpitis (NCT05227300), a randomized phase 4 study. The primary outcome is VAS Scores as Measures of Profoundness of Pulpal Anesthesia.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05227300 |
| Phase | Phase 4 |
| Condition | Symptomatic Irreversible Pulpitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 40 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Indiana University |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns patients with symptomatic irreversible pulpitis in mandibular molars. The registry record reports enrollment of 40 participants, with 20 assigned to each arm. Further eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
The intervention was buffered 2% lidocaine with 1:100,000 epinephrine. The arm description says sodium bicarbonate was added to make a 10% buffered solution. The record also lists an 8.4% sodium bicarbonate neutralizing additive solution.
Comparator
The comparator was standard, unbuffered 2% lidocaine with 1:100,000 epinephrine. Both arms therefore used the same stated lidocaine and epinephrine concentrations; the recorded distinction is buffering. Details about administration beyond the registry descriptions are not reported in the registry record.
Primary question
The primary endpoint asks how the mean Visual Analog Scale score, used as a measure of profoundness of pulpal anesthesia, compares between the two arms up to 20 minutes after drug administration. The study summary also identifies onset of pulpal anesthesia as a secondary outcome. The posted results do not report an onset result or a formal between-arm analysis.
The registry describes the study as a controlled, randomized comparison, with a parallel-group model. Its official title calls it double-blind, while the masking field records triple masking. The record does not identify which groups of people were masked, so the exact masking arrangement cannot be clarified from these fields alone.
The practical statistical question is not simply whether the arm averages differ. It is also whether the score definition and the observed spread support a clear interpretation, and how much uncertainty remains without a reported comparison or interval estimate. The posted means are descriptive results, not by themselves evidence of a statistically reliable difference.
3. Trial Design
This was a Phase 4, randomized, parallel-group study sponsored by Indiana University. The registry reports enrollment of 40 participants. The reported arm sizes are 20 for buffered 2% lidocaine with 1:100,000 epinephrine and 20 for the unbuffered preparation. The study status is completed. Its recorded start date is 2022-02-14 and its primary completion date is 2022-05-23.
The randomized allocation means participants were assigned to one of the two anesthetic arms, but the registry record does not describe the allocation sequence, concealment procedures, or any stratification. The record identifies a parallel model, meaning the arms are presented as separate groups rather than as repeated treatment periods for the same participants. It does not report additional design details such as the treatment procedure, dose volume, or rules for handling protocol deviations.
The official title describes a controlled, randomized double-blind study, whereas the registry masking field says triple masking. These labels are both present in the record; which people were masked and how masking was maintained are not reported in the registry record. The study summary describes the aims as comparing how well the anesthetic numbs the tooth nerve and whether time to numbness differs.
The primary endpoint is the mean VAS score, with a timeframe of up to 20 minutes after drug administration. The registry lists onset of pulpal anesthesia as a secondary outcome, but does not post its results. Although the record gives summary statistics for the primary outcome in each arm, it lists zero analyses. That distinction matters: arm-level summaries are available, but a formal inferential comparison is not reported. The registry record also does not report a sample-size justification, a prespecified analysis plan, or interim analyses.
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
| Stage | Buffered 2% Lidocaine With 1:100,000 Epinephrine | Unbuffered 2% Lidocaine With 1:100,000 Epinephrine |
|---|---|---|
| STARTED | 20 | 20 |
| COMPLETED | 20 | 20 |
| NOT COMPLETED | 0 | 0 |
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.
Population: All patients present with signs of symptomatic irreversible pulpitis on a mandibular molar.
| Characteristic | Unit | Buffered 2% Lidocaine With 1:100,000 Epinephrine | Unbuffered 2% Lidocaine With 1:100,000 Epinephrine | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 20 | 40 | |
| Age, Continuous | Years | 41.2 (SD 13.5) | 38 (SD 19.4) | 39.6 (SD 16.6) |
| Sex: Female, Male: Female | Participants | 15 | 8 | 23 |
| Sex: Female, Male: Male | Participants | 5 | 12 | 17 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | participants | 20 | 20 | 40 |
| Initial Visual Analog Scale (VAS) w/ a min score of 1 and max score of 10 (a 4+ is significant pain) | Units on a Scale | 7.8 (4 to 10) | 6.9 (5 to 10) | 7.35 (4 to 10) |
| Initial Electronic Pulp Test (EPT) less than 80 shows vital pulp (min stimulation is 1, max is 80) | Units on a scale | 42.9 (30 to 71) | 47.3 (14 to 72) | 45.1 (14 to 72) |
6. Primary Endpoint
The registry lists the primary outcome as VAS Scores as Measures of Profoundness of Pulpal Anesthesia, measured over Up to 20 minutes post-drug administration.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | Score on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the mean Visual Analog Scale (VAS) score used to represent profoundness of pulpal anesthesia. The timeframe is up to 20 minutes after drug administration. The record describes the scale as ranging from a minimum of 1 to a maximum of 10 and says scores from 4 to 10 indicate inadequate anesthesia, rather than comfortable and profound anesthesia.
A mean condenses the scores in an arm into a summary of the group’s central level. It is useful for describing an overall pattern, but it does not show how many participants had inadequate anesthesia or how scores were distributed across participants. The registry reports the full range alongside each mean, which gives some indication of the observed spread but does not replace participant-level results or an uncertainty estimate.
For the buffered arm, the reported mean is 3.1 and the full range is 0.0 to 8.0. For the unbuffered arm, the mean is 1.2 and the full range is 0.0 to 7.0. Both means are below the stated inadequate-anesthesia range, while both reported ranges extend into that range. Thus, the group averages alone cannot establish that every participant had a score considered comfortable and profound.
There is a record-level detail worth noticing: the stated scale minimum is 1, but both reported full ranges begin at 0.0. The registry does not explain this difference. It is therefore appropriate to describe the values as posted and to avoid assuming what a score of zero represents or how it was handled.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a mean VAS score of 3.1 for buffered lidocaine and 1.2 for unbuffered lidocaine. The respective full ranges are 0.0 to 8.0 and 0.0 to 7.0, with 20 participants in each arm. These are descriptive arm-level summaries. The record does not post a formal comparison, confidence interval, or p-value for this endpoint, and it lists zero analyses. The posted values therefore do not establish whether the observed difference between the arm means is statistically distinguishable from sampling variation.
The outcome definition gives scores from 4 to 10 as inadequate anesthesia. Each arm’s mean is below that stated range, but each arm’s reported full range includes scores within it. A mean below the threshold does not tell us how many participants scored at or above 4, nor whether the scores clustered near the mean or were spread across the range. The full range gives only the lowest and highest reported values; it does not reveal the distribution between them.
There is also a scale-description issue. The registry calls 1 the minimum of the VAS scale, yet the reported ranges begin at 0.0 in both arms. The record does not explain whether this reflects a coding convention, an amendment, or a reporting inconsistency. Without clarification, the scores can be described as posted, but the meaning of the zero values remains uncertain.
Precision cannot be assessed from the means and ranges alone. In general, an interval estimate would show the uncertainty around an estimated arm result or contrast under a specified method. No such interval is posted for the primary result. Nor does the record report a test or model for comparing arms. The absence of these quantities does not demonstrate that there is no difference; it means the registry data do not quantify the inferential uncertainty.
The secondary outcome is onset of pulpal anesthesia, but no result for it is included in the posted results. The study summary identifies time to numbness as an aim, yet the available registry information does not show how onset was defined, how it was summarized, or what was observed. Those questions cannot be answered from the primary VAS summaries.
The tables and plots should be read as displays of the posted results, not as substitutes for an unreported analysis. Any planning illustrations elsewhere on the page are not observed power and do not recover the trial’s own design rationale. The registry record does not report that rationale. The sponsor’s own analysis is not available in the record, so there is no sponsor analysis to take precedence over a recalculation.
9. Statistical Methods Explained
The results include arm-level means and full ranges for the primary VAS endpoint. The record reports 20 participants in each arm. It does not report an analysis method for comparing these summaries, and the registry lists zero analyses. The descriptions below explain general statistical concepts that help interpret such results; they are not claims about methods used in this trial.
What does a mean summarize?
In general, a mean is the sum of measured values divided by the number of observations. It gives a compact description of the group’s average score, but it does not show the individual scores or their pattern. Two groups can have similar means with different distributions, or different means with considerable overlap. For this trial, the registry posts the means but not participant-level scores, a standard deviation, or another measure of spread beyond the full range.
The mean is especially incomplete when the endpoint is interpreted using a threshold. The registry identifies scores from 4 to 10 as inadequate anesthesia. A mean does not reveal how many people crossed that threshold. A count or proportion above the threshold, along with a clearly defined analysis, would address a different question from a comparison of means. Such results are not reported in the registry record.
What does the full range tell us?
In general, a full range reports the lowest and highest observed values. It provides a boundary for the observations but says nothing about the density of scores between those boundaries. It is also sensitive to extreme observations. The posted ranges are 0.0 to 8.0 for the buffered arm and 0.0 to 7.0 for the unbuffered arm. These ranges show that values at or above the stated threshold occurred in each arm, but do not reveal how often.
The outcome description gives a scale minimum of 1 and maximum of 10, while the posted ranges start at 0.0. That mismatch should be treated as a reporting ambiguity rather than resolved by assumption. The registry record does not explain the scale coding or the zero values. A reader should not infer a clinical interpretation for zero that the record does not provide.
Why is an uncertainty estimate important?
In general, a confidence interval expresses the uncertainty around an estimate under a statistical model and its assumptions. An interval for an arm difference would help distinguish the estimated contrast from the precision with which it is known. The registry does not post an interval for the difference or for either arm mean. It also does not identify a test, model, or standard error used for the primary outcome.
A p-value, if reported, would address how compatible the data are with a specified null hypothesis under the chosen analysis. It would not by itself describe the size or practical meaning of an effect. No p-value is posted for the primary comparison. Since the methods and inferential results are not reported, it would be inappropriate to infer that a particular test was used or to reconstruct an official analysis from the summary values.
Why can distribution and outcome scale matter?
General statistical reasoning: a mean-based analysis is most straightforward when the outcome and its distribution are suitable for the model being used. A bounded score may have floor or ceiling concentrations, and its distribution may not be well represented by a symmetric model. Over-dispersion means that observed variability is larger than a model expects; when present, it can make standard errors too small if ignored. These are general considerations, not findings about this trial. The registry does not provide participant-level data or distributional diagnostics with which to assess them.
The threshold definition also suggests a possible alternative summary, such as reporting the number of scores in the inadequate range. That would require a prespecified handling of scores and a suitable analysis. The record does not report such a result or an analysis plan. It also does not explain how repeated VAS measurements, if any, within the stated timeframe were reduced to the reported outcome. The timeframe is up to 20 minutes after drug administration, but the timing schedule and summary rule are not reported.
What are planning illustrations?
General statistical reasoning: a sample-size calculation uses assumptions about the effect to be detected, variability, significance level, allocation, and analysis method. It is a planning exercise, not an outcome. The sample-size section contains planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such illustrations are not observed power and do not show what power the completed trial achieved.
The record does not report the trial’s own sample-size justification or the assumptions used when it was designed. The planning illustrations cannot fill in those missing protocol details. No new sample-size values or conclusions about adequacy should be inferred from the arm means alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity plan. It identifies the VAS score as the primary outcome and onset of pulpal anesthesia as a secondary outcome, and it reports two outcome measures overall. It does not describe whether additional time points, subgroup comparisons, or multiple endpoint analyses were planned. Since multiplicity procedures are not reported, readers cannot determine how the study intended to account for testing more than one question.
The secondary outcome is named, but no onset results are posted. The primary outcome has arm-level summaries, but the record lists zero analyses. The statistical analysis plan, including any planned contrast, model, or adjustment, is not reported in the registry record. The record also does not report whether analyses were prespecified or whether any analysis changed after the study began.
Missing-data handling is not reported. The registry gives 20 participants per arm for the outcome summaries, but does not state whether these are all randomized participants, whether any observations were missing, or how incomplete records were treated. It also does not describe exclusions after randomization, protocol deviations, or the analysis population. Therefore, the posted arm sizes should not be assumed to represent a specified intention-to-treat or per-protocol analysis set.
In general, missing-data methods and analysis populations can affect how results are interpreted, particularly when missingness differs by arm or relates to the outcome. That is a general methodological point, not a claim that missing data occurred. The registry record does not provide the information needed to evaluate it.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Buffered 2% Lidocaine With 1:100,000 Epinephrine | 0 | 20 | 0.0% |
| Unbuffered 2% Lidocaine With 1:100,000 Epinephrine | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Buffered 2% Lidocaine With 1:100,000 Epinephrine | 0 of 20 |
| Unbuffered 2% Lidocaine With 1:100,000 Epinephrine | 0 of 20 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0.0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Buffered 2% Lidocaine With 1:100,000 Epinephrine | 0 of 20 |
| Unbuffered 2% Lidocaine With 1:100,000 Epinephrine | 0 of 20 |
The posted safety figures list 20 participants at risk in each arm. For buffered lidocaine, the registry reports 0 serious adverse events, 0 other adverse events, and 0 deaths. For unbuffered lidocaine, it likewise reports 0 serious adverse events, 0 other adverse events, and 0 deaths. The list of top serious-event terms is empty.
These figures mean that no events are recorded in the posted registry summary for the listed categories. They should not be interpreted as proof that no adverse experiences occurred outside the reporting definitions or collection period. The registry record does not provide event definitions, monitoring details, the safety observation period, or further information about how events were solicited and classified.
In general, a zero count in a study summary is a statement about the recorded observations, not proof that an event is impossible. The figures also do not by themselves establish comparative safety, especially without a reported inferential analysis or detailed event descriptions. The results are limited to the counts shown in the registry record.
12. What the Result Does, and Does Not, Mean
The posted primary results describe two arm averages and their observed ranges. The buffered arm has a reported mean VAS score of 3.1, with a full range of 0.0 to 8.0. The unbuffered arm has a mean of 1.2, with a full range of 0.0 to 7.0. Each arm includes 20 participants. These figures describe the registry’s summary results; they do not, on their own, establish a reliable between-arm difference or its precision.
The registry defines scores from 4 to 10 as inadequate anesthesia. Both means fall below that range, but the ranges extend into it. The mean does not tell us how many participants had scores in the inadequate range, and the record does not post that count. In addition, the recorded scale minimum of 1 does not align with the ranges beginning at 0.0. The registry does not explain the discrepancy.
The result does not answer the secondary question about onset, because no onset result is posted. Nor does the record provide a formal statistical comparison, confidence interval, p-value, or a detailed analysis plan. Consequently, the available summaries cannot determine the precision of a contrast or whether it meets a statistical criterion.
In general, a randomized design can support a comparison between assigned groups when the allocation, conduct, outcome measurement, and analysis are adequately described. Here, the registry records randomized allocation and equal reported arm sizes, but further design and analysis details are not reported. The interpretation must remain anchored to the descriptive results that are actually posted.
These findings should not be translated into medical advice or a claim that either anesthetic does or does not work. The record supports a narrow statistical description: it reports arm means, ranges, and safety counts, while leaving important inferential and measurement details unresolved. A fuller interpretation would require the missing analysis and clarification of the scale reporting.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it illustrates the difference between reporting group summaries and reporting a comparison. The registry gives a mean and full range for each arm, but lists zero analyses. Readers can see the observed summaries, yet cannot see a reported estimate of the between-arm contrast or its uncertainty. That distinction is central when interpreting randomized studies: descriptive values are informative, but they do not supply all the evidence needed for an inferential conclusion.
The endpoint also combines a continuous score with a clinically defined threshold. A mean summarizes the score level, while the threshold distinguishes scores described as inadequate from those considered comfortable and profound. Those summaries answer different questions. Reporting only the mean and range does not show the frequency of scores in the inadequate category. The registry’s scale minimum of 1, alongside observed ranges beginning at 0.0, adds a measurement-reporting issue that should be clarified before drawing stronger conclusions.
The design record contains other points that matter for interpretation. It identifies randomized allocation and a parallel model, but does not describe allocation procedures or analysis populations. The official title says double-blind, while the masking field says triple masking; the record does not specify who was masked. These details affect how readers assess the design, but cannot be reconstructed from the available fields.
The planning illustrations also demonstrate why planned sample size and observed outcomes should be kept separate. Those illustrations are based on an observed effect and stated assumptions; they are not observed power and are not the trial’s design justification. The registry does not report its own sample-size rationale. Overall, the trial is a useful case for distinguishing what a posted table can show from what requires a specified analysis, uncertainty estimates, and transparent outcome definitions.
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.
Several trial-specific limitations in the registry record constrain interpretation. First, the primary result is presented as arm-level means and ranges, without a formal comparison, confidence interval, p-value, or stated analysis method. The record lists zero analyses. As a result, the precision of the apparent difference between the means is not reported.
Second, the scale description and reported ranges do not fully align: the VAS is described as having a minimum of 1, while both ranges begin at 0.0. The registry does not explain the zero values or describe whether the scale was coded differently for the posted results. This limits interpretation of the endpoints of the observed ranges.
Third, the registry does not report the distribution of individual scores or the number of participants whose scores fell in the stated inadequate range of 4 to 10. The mean and full range cannot answer that threshold-based question. The secondary outcome, onset of pulpal anesthesia, is named but its results are not posted.
Important design and conduct details are also absent. The record does not describe allocation concealment, the people masked, the timing and handling of VAS measurements, missing data, analysis populations, protocol deviations, or the planned statistical analysis. The official title’s double-blind wording and the triple-masking field are both recorded, but the masking roles are not explained. The record also does not provide a sample-size justification. These are limits of the registry information, not evidence that any particular procedure was or was not used.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Buffered vs. Unbuffered Local Anesthesia in Mandibular Molars Diagnosed With Symptomatic Irreversible Pulpitis — NCT05227300.
- Registry record last updated 2024-05-14; status last verified 2024-04.
- Results first posted 2024-05-14.
- 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.
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18. Record Summary
This completed Phase 4 randomized parallel-group study, sponsored by Indiana University, enrolled 40 participants with symptomatic irreversible pulpitis in mandibular molars. It compared buffered and unbuffered 2% lidocaine with 1:100,000 epinephrine, with 20 participants reported in each arm. The record gives the primary VAS endpoint timeframe as up to 20 minutes after drug administration and lists onset of pulpal anesthesia as a secondary outcome.
The primary results are posted as means and full ranges: 3.1 and 0.0 to 8.0 for buffered lidocaine, and 1.2 and 0.0 to 7.0 for unbuffered lidocaine. No formal primary comparison is posted, and the record lists zero analyses. The outcome description states a scale minimum of 1 despite ranges beginning at 0.0, an issue the record does not explain. Safety counts show 0 serious events, 0 other events, and 0 deaths in each arm. The registry does not report onset results, a statistical analysis plan, or a sample-size justification.