Safety and Effectiveness of Kovacaine Nasal Spray for Dental Anesthesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Effectiveness of Kovacaine Nasal Spray for Dental Anesthesia (NCT01302483), a randomized phase 2 study. The primary outcome is Pulpal Anesthesia.

2. Clinical Question

3. Trial Design

The registry describes a phase II, single-center, randomized, double-blind, active-treatment-controlled, parallel-group study. Its official title identifies the purpose as evaluating efficacy of Kovacaine Nasal Spray for anesthetizing maxillary teeth in healthy dental patients. The record lists enrollment of 45 and marks the study completed. The recorded study start is 2008-12 and primary completion is 2009-01.

Participants were assigned to Kovacaine Nasal Spray or lidocaine injection. The nasal spray arm used 3% tetracaine HCL with 0.05% oxymetazoline HCL, delivered via 3 sprays (100 uL) in each nostril. The injection arm used .5 to 1 catridge of 2% lidocaine HCL with 1:100,000 epinephrine. The record calls the study double-blind but does not identify which roles were masked or describe how masking was maintained. The randomization method, allocation concealment, and the procedure for treatment assignment are not reported in the registry record.

The primary outcome was the number of participants who did not need rescue anesthesia to complete the study dental procedure. It was assessed throughout treatment, up to 60 minutes, and the stated analysis population was intention to treat. The record also lists outcomes concerning soft tissue anesthesia duration and changes in pulse, blood pressure, and pulse oximetry. Numeric results are posted for pulse and pulse oximetry, while numeric results for soft tissue anesthesia duration and blood pressure are not reported in the registry record.

The registry does not report the trial's original sample-size justification, planned analysis method, or a detailed protocol for handling missing observations. Those omissions limit what can be concluded about the original design choices; they do not change the interpretation of the recorded group counts and comparison estimates.

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

Analysis population for the primary outcome, as defined in the registry: Intention to treat

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 Pulpal Anesthesia, measured over Continuous throughout dental treatment period (up to 60 minutes).

The primary endpoint is a binary measure at the participant level: whether a participant completed the study dental procedure without needing rescue anesthesia. The registry describes the outcome as the number of participants who did not need rescue anesthesia, and identifies the analysis population as intention to treat. The assessment period was continuous throughout dental treatment, up to 60 minutes.

This endpoint addresses a practical feature of the study's anesthesia question: whether the assigned approach was recorded as sufficient to complete the procedure without additional anesthesia. It does not directly quantify the intensity of pain, the degree of pulpal numbness, or how long anesthesia lasted. Soft tissue anesthesia duration was listed separately as a secondary outcome, which underscores that duration and the primary completion criterion are different measures.

For a binary endpoint, each participant contributes to one of two outcome categories: meeting or not meeting the stated criterion. The group counts can therefore be described as proportions, and their difference can be expressed as a risk difference. Such a measure is interpretable in the outcome's original terms, but it is still an estimate from a limited study population. A recorded need for rescue anesthesia is the endpoint definition; the registry does not provide more detailed criteria for deciding when rescue was required.

The outcome is useful for comparing the recorded completion criterion between the randomized groups. It should not be treated as a comprehensive assessment of anesthesia quality or as a substitute for other outcomes that were listed but not numerically reported in the registry record.

7. Results Posted in the Registry

• Lidocaine Injection: 93.3% (14/15) versus 83.3% (25/30) on control; risk difference 10.0 percentage points (95% CI -8.4 to 28.4), risk ratio 1.12 (0.91–1.38); unadjusted two-proportion z-test p = 0.352.

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.

Maximum Change in Pulse From Baseline

• 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 deviations.
• Result:
  • Lidocaine Injection: mean -6.60 versus -11.13 on control; difference 4.53 (95% CI -4.08 to 13.14), standardized effect d = 0.38; z-test p = 0.303.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lidocaine Injection and the control. The interval gives the range of effects that remain compatible with the data.

Maximum Change in Pulse Oximetry From Baseline

• 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 deviations.
• Result:
  • Lidocaine Injection: mean -0.80 versus 0.17 on control; difference -0.97 (95% CI -2.61 to 0.67), standardized effect d = -0.39; z-test p = 0.246.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lidocaine Injection and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes provide a limited view of recorded physiological changes alongside the primary completion-without-rescue measure. The registry lists soft tissue anesthesia duration and maximum changes in pulse, blood pressure, and pulse oximetry. Numeric summary comparisons are posted for pulse and pulse oximetry. Numeric results for soft tissue anesthesia duration and blood pressure are not reported in the registry record.

The broad pattern in the posted secondary comparisons is uncertainty rather than a clear separation between the groups: both unadjusted confidence intervals include no difference, and neither comparison is precise enough to establish that the groups' underlying changes are the same. These outcomes address different aspects of the study from the primary endpoint. They do not determine whether a participant completed the dental procedure without rescue anesthesia, and they should not be substituted for the primary result.

Secondary findings usually carry less inferential weight when many outcomes or comparisons are considered without a prespecified multiplicity strategy. Looking across multiple outcomes increases the chance that an apparently notable result arises by chance, while adjustment or a hierarchy of tests can change how evidence is interpreted. The registry does not report a multiplicity plan or detailed statistical analyses for these secondary measures. Their unadjusted p-values should therefore be treated as exploratory descriptions, not as independent confirmation of the primary finding.

The secondary data do not resolve the uncertainty in the primary comparison. Nor can the absence of numerical results for two listed secondary outcomes be interpreted as evidence of no change. The record's listing of an outcome establishes that it was named as a secondary outcome, but the registry record does not report its numeric result. A full account of missing observations, analysis populations, and planned comparisons is also not reported in the registry record.

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

• Soft Tissue Anesthesia Duration
• Maximum Change in Pulse From Baseline
• Maximum Change in Blood Pressure From Baseline
• Maximum Change in Pulse Oximetry From Baseline

9. Statistical Interpretation

10. Statistical Methods Explained

The registry posts a binary primary outcome: participants who did not need rescue anesthesia to complete the dental procedure. For a binary outcome, a group proportion expresses the share of participants meeting the criterion. Comparing those proportions on the risk-difference scale gives an absolute contrast in the same outcome units. A positive or negative sign depends on the order used for the groups; the posted comparison is expressed for lidocaine injection relative to Kovacaine Nasal Spray.

What does the risk difference describe?

The risk difference is the estimated difference between the two group proportions. The posted estimate is 0.1. This is an absolute contrast, not a relative percentage change. Its confidence interval crosses zero, meaning that values compatible with the data include a difference in either direction. The interval's breadth is relevant: it indicates that the estimate does not pin down the size of the group contrast precisely.

The record also includes relative measures, the risk ratio and odds ratio. A risk ratio compares the group proportions as a ratio; an odds ratio compares the odds of meeting the endpoint. These measures use different scales and need not have the same numerical interpretation as a risk difference. They do not remove uncertainty from the small group summaries, and they should be interpreted alongside the endpoint's actual counts and the confidence interval. A ratio near its null value represents no contrast on that ratio scale, just as zero is the null value for a difference scale.

How should the p-value be read?

The primary unadjusted p-value is 0.352. In general, a p-value describes how unusual an estimate at least as extreme as the observed one would be under a specified null hypothesis and the assumptions of the test. It is not the probability that the null hypothesis is true, a measure of clinical importance, or evidence by itself that two treatments are equivalent. The registry does not report the original statistical test or a prespecified decision threshold, so the posted p-value should be read as an unadjusted comparison rather than as a complete account of the trial's analysis plan.

An unadjusted estimate is a comparison without an adjustment for other variables or for multiple testing. The registry record does not report an adjusted model for the primary endpoint. Random assignment is intended to support comparison of groups, but it does not guarantee balance on every characteristic in a limited sample. Because baseline characteristics and adjustment methods are not described in the posted results, the degree to which any covariates were considered is not reported in the registry record.

What do the continuous secondary outcomes measure?

For the posted secondary outcomes, the registry gives group means and standard deviations for maximum change from baseline. A mean summarizes the average recorded change, while a standard deviation describes variability among observations around that mean. The mean difference compares group averages. Its confidence interval reflects uncertainty in the estimated contrast; an interval spanning zero does not establish that the underlying group means are exactly equal.

The reported comparison calculations use group summary statistics. They are unadjusted and should not be mistaken for a complete model-based analysis. For pulse, the reported mean difference is 4.53, with a confidence interval from -4.082 to 13.14 and an unadjusted p-value of 0.303. For pulse oximetry, the reported mean difference is -0.97; its confidence interval includes zero, and its unadjusted p-value is 0.246. These summaries are secondary to the primary endpoint and are not reported analyses from a described statistical plan. The registry lists maximum change in blood pressure and soft tissue anesthesia duration as secondary outcomes, but numeric results for them are not reported in the registry record.

Why do variability and uncertainty matter?

General statistical explanation: variability affects how precisely a group mean or difference can be estimated. When outcomes vary substantially among participants, a group average can be an incomplete description of the spread of individual observations. A confidence interval combines the estimated contrast with its uncertainty under the calculation's assumptions. A narrow interval would indicate greater precision than a wide interval, but neither width alone nor a p-value determines whether a difference is important to patients or researchers.

Over-dispersion is a general concern when observed variability is greater than a model assumes. In that situation, standard errors based on an under-dispersed model can be too small, producing intervals that are too narrow and tests that appear more decisive than warranted. This general issue is not a claim about the methods used in this trial: the registry does not report an analysis model for the primary outcome, and the posted secondary results are summaries rather than a detailed account of model diagnostics.

What analysis details are unavailable?

The registry record does not report the planned statistical analysis, covariate adjustments, missing-data procedure, interim analyses, or a multiplicity strategy. It also does not provide a sample-size justification from the original design. Those items cannot be reconstructed from the observed group summaries. In particular, the listed planning illustrations are not evidence about the trial's original design assumptions or its observed power.

The primary analysis population is identified as intention to treat, but the record does not explain how participants with missing endpoint data, protocol deviations, or other analysis complications were handled. The posted counts are therefore best read as the record's reported group results, not as evidence that all possible analytical decisions have been documented.

11. Confidence Intervals and Precision

Precision concerns the range of values reasonably compatible with an estimate, under the assumptions used to construct its confidence interval. For the primary risk difference, the posted estimate is 0.1, and the interval extends below and above zero. Thus, the data do not determine the direction of the underlying difference precisely. The interval does not rule out no difference, nor does it rule out differences in either direction.

The primary unadjusted p-value, 0.352, is consistent with this uncertainty, but the interval gives more information about the possible size and direction of the contrast. Neither statistic establishes equivalence. Equivalence requires a prespecified margin and an analysis designed to assess whether the uncertainty lies within that margin; such a margin and plan are not reported in the registry record.

For the secondary pulse comparison, the confidence interval runs from -4.082 to 13.14. For pulse oximetry, the interval also includes zero. These intervals describe unadjusted mean differences and are not a substitute for the omitted original analysis plan. The results should be treated as imprecise estimates rather than definitive evidence of no change between groups.

The sizes of the groups affect precision: the registry reports 30.0 participants in the Kovacaine Nasal Spray arm and 15.0 in the lidocaine injection arm. The limited group sizes make it difficult to estimate modest differences precisely, particularly for outcomes with variability. The registry provides no posted confidence intervals for the individual arm summaries, and it does not report a detailed missing-data analysis. Precision should therefore be judged from the posted comparisons and their stated limitations, not inferred from the point estimates alone.

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 expressed as participants per arm for the non-time-to-event outcomes in this trial. They are not totals across arms or total event counts. The illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects equal to 100%, 75%, and 50% of the observed effect. The sample-size assumptions for the original trial are not reported in the registry record.

The 80% power column gives the illustrative participants per arm for a design with an 80% chance of detecting the specified effect under the planning assumptions, if that effect and those assumptions held. The 90% power column gives the corresponding planning count for a 90% chance. These are design-planning concepts, not guarantees for a future study: the actual chance of detecting an effect depends on the true effect, variability, analysis choices, and whether the assumptions are appropriate.

For the primary endpoint, the illustration lists 161 participants per arm for 80% power and 215 for 90% power when planning for 100% of the observed effect. For 75% of the observed effect, it lists 313 and 419 participants per arm; for 50%, it lists 763 and 1,021. The secondary-outcome planning figures are separate illustrations based on their own observed estimates. Smaller effects need more participants to detect, all else being equal, which is why the planning counts increase as the assumed fraction of the observed effect decreases.

These are planning illustrations, not observed power. They are calculated from the observed effect and stated assumptions, and do not reveal the trial's original sample-size rationale or establish what the study was designed to detect.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.833; treatment proportion p₁ = 0.933; average p̄ = 0.883.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4540 = 0.8898.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4485 = 0.3774.
4. n = (0.8898 + 0.3774)² / (0.1000)² = 160.6, rounded up to 161 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
p0 <- 0.833333333333333                          # control proportion
p1 <- 0.933333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1302483)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 161 (80% power), 215 (90% power)
 75% of observed effect: n per arm = 313 (80% power), 419 (90% power)
 50% of observed effect: n per arm = 763 (80% power), 1,021 (90% power)
power.prop.test: 160.6 
Simulated power at n = 161 per arm: 0.815 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when researchers assess several outcomes, time points, or contrasts. With more opportunities to find a result, the chance of at least one apparently unusual finding can increase. Statistical plans commonly address this through a prespecified primary outcome, an ordered testing strategy, or adjustment for multiple comparisons. The registry identifies pulpal anesthesia as the primary outcome and lists several secondary outcomes, but a multiplicity strategy is not reported in the registry record.

The primary comparison is therefore best interpreted on its own terms, while secondary comparisons should be considered less definitive. The posted secondary p-values are unadjusted. The registry record does not say whether multiplicity was addressed in another analysis or whether particular secondary outcomes were intended to be confirmatory. No reported secondary analyses are listed for the posted summary measures.

The primary outcome identifies the intention-to-treat population, but the registry record does not describe how missing outcomes were handled within that population. It does not report participant flow, reasons for missingness, imputation, sensitivity analyses, or whether any participants were excluded from a particular analysis. The available counts should not be taken as proof that no missing data or protocol deviations occurred; those details are not reported in the registry record.

The record also does not report the trial's original statistical analysis plan, covariate adjustment, interim analyses, or a sample-size justification. Without those details, it is not possible to assess whether the posted comparisons follow a prespecified plan, whether other analyses were undertaken, or how the investigators intended to address multiple testing and missing information. This uncertainty is about the documentation available in the registry record, not evidence that a particular procedure was or was not used.

These gaps matter because analytical choices can affect estimates, intervals, and p-values. They reinforce the need to distinguish the posted summaries and unadjusted recalculations from a complete report of the trial's statistical methods. They also prevent a robust reconstruction of the original analysis decisions.

15. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 30 participants at risk in the Kovacaine Nasal Spray group and zero among 15 at risk in the lidocaine injection group. These are observed counts in this study, not proof that serious events cannot occur. A study with limited group sizes cannot reliably characterize uncommon events, and the record does not provide serious adverse event terms.

Other adverse events are recorded for the Kovacaine Nasal Spray group, with 10 participants affected among 30 at risk, and none for the lidocaine injection group, with 0 among 15 at risk. The registry does not provide event terms in the posted safety details, so the nature and clinical importance of these other events cannot be assessed from the counts alone.

Death counts are not reported in the registry record. The safety figures should be read as registry-reported observations over the recorded study period, not as a complete characterization of risk or a basis for comparing treatments beyond this study.

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

The primary result describes the proportion of participants recorded as completing the study dental procedure without rescue anesthesia. That criterion was met by 25.0 of 30.0 participants in the Kovacaine Nasal Spray group and 14.0 of 15.0 in the lidocaine injection group. The posted risk-difference estimate is 0.1 for lidocaine injection relative to Kovacaine Nasal Spray, with an unadjusted p-value of 0.352. The interval includes zero and extends in both directions, so the estimate does not establish a clear difference between groups.

The result does not show that the treatments are equivalent. Equivalence would require an explicit margin and an analysis designed to determine whether the full uncertainty interval lies within that margin; these are not reported in the registry record. Likewise, the result does not establish superiority in either direction. A nonsignificant p-value is not evidence that a difference is absent, especially when the estimate remains imprecise.

The endpoint has a specific scope: no need for rescue anesthesia to complete the study procedure during the treatment period, up to 60 minutes. It is not a direct measurement of pain intensity, patient satisfaction, or the duration of soft tissue anesthesia. The registry lists other secondary outcomes, but numeric findings are available only for pulse and pulse oximetry among those additional outcomes represented in the posted summaries. The results for blood pressure and soft tissue anesthesia duration are not reported in the registry record.

The safety counts likewise describe recorded events in this study and do not establish that serious events are impossible or that the two approaches have the same safety profile. The study's phase II, single-center design and limited enrollment constrain the precision and generalizability of the findings. Broader conclusions would require evidence beyond the posted results, including fuller reporting of eligibility, participant flow, analysis methods, and outcomes.

In statistical terms, the record supports a description of the observed groups and an uncertain estimated contrast. It does not justify a treatment recommendation or a conclusion that either approach works or does not work. The distinction between observed data and what those data can establish is central to reading the result.

17. Why This Trial Matters Statistically

This trial illustrates why an outcome's definition matters. The primary endpoint is not a general rating of anesthesia quality; it is whether rescue anesthesia was needed to complete a specified dental procedure. The result can therefore be interpreted directly against that criterion, while avoiding broader claims about pain, satisfaction, or duration that the endpoint does not measure.

It also shows why point estimates should be read with their uncertainty. The primary estimate is a risk difference, a scale that expresses an absolute contrast in the recorded outcome. Its confidence interval crosses zero, and the unadjusted p-value does not establish a difference. Reporting the estimate and its interval together helps distinguish the observed direction from the range of comparisons still compatible with the data.

The study's group sizes and single-center phase II design make the precision and scope of conclusions important. A result from this setting should not automatically be generalized to other dental populations, procedures, or practice settings; detailed eligibility and setting information beyond the registry description is not reported in the registry record. The record also does not include the original sample-size justification or a detailed statistical analysis plan.

Finally, the secondary outcomes and safety counts demonstrate the importance of complete outcome reporting and multiplicity context. Some secondary measures are listed without numeric results, while available secondary comparisons are unadjusted. Clear distinctions among the primary endpoint, exploratory comparisons, and unreported results help readers avoid treating every statistic as equally conclusive.

18. 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 principal limitations specific to this trial are its phase II, single-center design and the limited group sizes recorded for the primary comparison. These features restrict precision and make it difficult to draw conclusions about smaller differences or uncommon safety events. The registry's enrollment entry is 45, while the arm summaries report 30.0 participants for Kovacaine Nasal Spray and 15.0 for lidocaine injection.

The primary outcome is a narrowly defined completion criterion: participants who did not need rescue anesthesia to complete the procedure. The registry does not report more detailed rescue criteria or numeric results for soft tissue anesthesia duration, which is listed as a secondary outcome. This limits interpretation of anesthesia characteristics beyond the primary endpoint.

The record calls the study double-blind but does not identify which people were masked, how masking was maintained, or whether treatment assignment could be discerned. It also does not report allocation concealment or the randomization method. These are documentation limits; they do not establish that any particular trial procedure was inadequate.

Additional limitations include the absence of a posted original statistical analysis plan, sample-size justification, multiplicity strategy, missing-data procedure, and detailed participant-flow information. Numeric results for blood pressure and soft tissue anesthesia duration are not reported in the registry record. The posted secondary comparisons are unadjusted, and the safety record does not include serious-event terms. Taken together, these gaps restrict assessment of the complete analysis and the breadth of conclusions supported by the registry results.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Safety and Effectiveness of Kovacaine Nasal Spray for Dental Anesthesia — NCT01302483.
• Registry record last updated 2015-06-17; status last verified 2015-06.
• Results first posted 2015-06-17.
• 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.

22. Record Summary

NCT01302483 is a completed phase II, single-center, randomized, double-blind, active-treatment-controlled, parallel-group study of Kovacaine Nasal Spray versus lidocaine injection for maxillary dental anesthesia. The registry lists enrollment of 45. The primary outcome was the number of participants who did not need rescue anesthesia to complete the study procedure, assessed throughout treatment up to 60 minutes, in an intention-to-treat population.

The posted primary counts were 25.0 of 30.0 in the Kovacaine Nasal Spray group and 14.0 of 15.0 in the lidocaine injection group. The estimated risk difference was 0.1 for lidocaine injection relative to Kovacaine Nasal Spray, with an unadjusted p-value of 0.352 and an interval spanning zero. The registry reports no serious adverse events in either group. The original sample-size rationale, detailed statistical plan, and several listed secondary-outcome results are not reported in the registry record.