The Effect of Intravenous Lidocaine on Post-extubation Laryngospasm: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Intravenous Lidocaine on Post-extubation Laryngospasm (NCT01445847), a randomized na study. The primary outcome is Number of Patients With Laryngospasm Postoperatively.

2. Clinical Question

The question is about an outcome counted in participants, rather than a continuous measurement such as a score average. The posted results report 0 participants with laryngospasm in the lidocaine group and 7 in the placebo group; each outcome group is reported as containing 36 participants. Those counts describe the posted outcome data, not necessarily everyone enrolled in the trial.

The registry record says the trial was terminated by a data monitoring committee due to safety concerns. It does not state the committee’s reasoning in greater detail, nor does it provide further information about how the termination affected the conduct or analysis. The clinical question can therefore be stated from the planned comparison and the posted endpoint, but the context of the termination remains limited.

3. Trial Design

The study is listed as a randomized, quadruple-masked, parallel-group trial. The listed interventions are lidocaine and placebo, with the placebo described as normal saline. Quadruple masking indicates that the registry characterizes the trial as masked at four roles or levels, but the record does not identify those roles. Further details about how randomization was generated or implemented are not reported in the registry record.

The registry lists enrollment as 134. That figure should not be read as the number included in the posted primary outcome comparison: the outcome data give 36 participants in each group. The record does not explain the relationship between enrollment and the groups included in the outcome analysis, or why those reported group sizes differ from the enrollment figure.

The trial was sponsored by King Saud University. The recorded start was 2012-01, the primary completion was 2012-04, and the status is terminated. The primary outcome population description says that the trial was terminated by a data monitoring committee due to safety concerns. More detailed stopping criteria, the timing of the committee’s decision, and any effects on follow-up or data collection are not reported in the registry record.

The study summary describes its aim as assessing intravenous lidocaine’s effect on postoperative laryngospasm in adults. The outcome was the number of participants with laryngospasm within the first 15 minutes post-dose. The record reports a single outcome measure and a single analysis. It does not describe the randomization ratio, protocol deviations, participant flow, or the analysis population in enough detail to establish how participants moved from enrollment to the posted comparison.

These features define the broad design, but they do not resolve important operational questions. For example, masking is identified but its implementation is not described, and the registry record does not report the planned sample-size justification or a full statistical analysis plan.

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: Patients were able to refuse to participate before anesthesia induction start. Therefore, patients may excluded from the study due to that reason and we decided to start assignment to groups randomly when anesthesia is induced to the patient.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Trial was terminated by data monitoring committee due to safety concerns

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 Number of Patients With Laryngospasm Postoperatively, measured over within first 15 minutes post-dose.

The primary endpoint is the number of participants with laryngospasm postoperatively, assessed within the first 15 minutes post-dose. It is a binary participant-level outcome for the posted comparison: a participant either met the recorded laryngospasm outcome or did not. The outcome description also gives four grades: no laryngospasm, stridor or partial laryngospasm, complete laryngospasm, and cyanosis. The registry does not explain how those grades were combined to define the reported participant count.

Counting participants with an event is useful when the research question concerns whether an event occurred, rather than its average severity or duration. A comparison of proportions can then describe how frequently the event was recorded in each group. The endpoint’s short stated assessment window focuses the outcome on the immediate post-dose period; it does not describe events outside that window.

In general, a clearly specified endpoint helps readers understand what the comparison represents and when it was measured. Here, the record supplies the endpoint name, timing, and grade descriptions, but does not report further details about assessment procedures, adjudication, or the precise threshold used to classify a participant as having laryngospasm. Those details matter when interpreting a count and cannot be inferred from the grade labels alone.

The posted counts are 0 for lidocaine and 7 for placebo, with 36 participants reported in each group. They describe the recorded endpoint in the posted results, not all possible respiratory outcomes or later events.

7. Results Posted in the Registry

• Lidocaine: 0.0% (0/36) versus 19.4% (7/36) on control; risk difference -19.4 percentage points (95% CI -32.4 to -6.5); unadjusted two-proportion z-test p = 0.005.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted outcome is a count of participants with an event. For this kind of endpoint, a common summary is the proportion with the event in each group. A risk difference compares those proportions by subtracting the comparator-group proportion from the intervention-group proportion. Its value is expressed on the probability scale: zero represents no difference, while a negative value in this comparison means the observed proportion is lower in the lidocaine group. The recalculation is identified as an unadjusted risk difference.

In general, an unadjusted comparison uses the group outcomes without accounting for other participant characteristics or design variables. It can be easy to interpret, but it does not answer whether adjustment would change the estimate. The registry record does not report an adjusted analysis or a covariate-adjustment plan. The posted comparison therefore should not be described as adjusted for other factors.

A confidence interval gives a range of values compatible with the data under the statistical method’s assumptions. Its width reflects uncertainty as well as the amount and pattern of information in the data. For a risk difference, an interval entirely on one side of zero indicates that the data are not compatible with zero difference at the corresponding confidence level under that method. This statistical feature does not establish a clinical interpretation, prove causation, or resolve possible bias in outcome measurement or participant selection.

A p-value is a measure of how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions were correct. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The recalculated comparison reports an unadjusted p-value of 0.005. The sponsor analysis reports p < 0.05. Those values accompany different presentations of the comparison and should not be treated as interchangeable proof of a particular clinical conclusion.

The registry’s reported sponsor method is “Comparison of proportions,” with the result described as a percentage and accompanied by a 95% confidence interval. The recalculation is separately described as a risk difference. A comparison of proportions is a broad methodological description; the record does not provide enough detail to identify every computational choice behind the sponsor’s result. As the two results are discrepant, the sponsor’s own analysis takes precedence in reporting what the sponsor concluded statistically. The recalculated estimate remains a simple, unadjusted re-calculation from posted summary statistics, not a replacement for the sponsor analysis.

With binary outcomes, the observed event count and group size determine each group’s observed proportion. When event counts are sparse, estimates and intervals may be sensitive to the method used, particularly when a group has no observed events. In general, different methods for constructing intervals or testing proportions can give different numerical results in sparse data. The record does not specify the exact method used for the recalculation beyond its unadjusted risk-difference description, nor does it fully specify the sponsor’s computation. This is relevant to the discrepancy and to the precision of the comparison.

The study’s reported counts are 0 events in the lidocaine group and 7 in the placebo group. General statistical interpretation distinguishes the observed count from the underlying event probability: the count is what was recorded in these groups, while the probability is an uncertain quantity estimated from the data. The counts alone do not establish what would occur in another group of participants or under different study conditions.

The record lists one primary outcome measure and one analysis. That does not establish the full scope of statistical testing or whether any analyses were conducted but not posted. It also does not specify a multiplicity procedure. In general, when several outcomes or repeated tests are considered, the chance of at least one apparently unusual result may increase; methods to address that issue depend on the planned testing strategy. The registry record does not report such a strategy.

Sample-size calculations are planning tools, not descriptions of observed evidence. The planning illustration associated with this record is based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; it considers detecting a stated fraction of that observed effect. Such an illustration does not show the trial’s original design rationale, and it is not observed power. The trial’s own sample-size justification is not reported in the registry record. No calculated sample-size result should be interpreted as an additional observed trial outcome.

Finally, enrollment and analysis counts have different roles. Enrollment is recorded as 134, while the posted outcome comparison reports 36 participants per group. Without a participant-flow account or analysis-population definition, those figures cannot be reconciled from the registry record. It would be inappropriate to infer how many participants were excluded, whether any data were missing, or why the posted analysis includes the reported groups.

10. Confidence Intervals and Precision

The recalculated risk difference has a confidence interval whose lower and upper limits are both below zero. This indicates that the full reported interval is on the side corresponding to a lower event proportion in the lidocaine group, under the recalculation’s method. The interval’s numeric limits are not repeated because the posted limits have more than three decimal places, while values in this discussion are limited to three decimal places. The registry reports an unadjusted p-value of 0.005 for that comparison.

A confidence interval is useful because it presents uncertainty about the estimated difference rather than only a single point estimate. In general, a narrower interval indicates greater precision for the chosen method, while a wider interval indicates less precision. Precision is not the same as absence of bias: an interval does not account for problems such as incomplete outcome ascertainment, unclear analysis populations, or systematic differences between groups.

The sponsor’s reported result is a percentage of 5, with a 95% confidence interval from 1.7 to 9.1 and p < 0.05. This is a distinct presentation from the recalculated risk difference, and the registry record does not provide enough computational detail to reconcile the two results. The sponsor analysis takes precedence as the sponsor’s own reported analysis because the figures are discrepant.

Both estimates must be read in light of the outcome counts: 0 in the lidocaine group and 7 in the placebo group, with 36 participants reported in each. In general, a limited number of events can leave estimates sensitive to the specific statistical method. The registry does not report enough detail to assess all sources of uncertainty, including missing outcome data or the relation between the enrollment figure and the analysis groups. Thus, the interval communicates statistical uncertainty under a method, not certainty about the underlying effect or its applicability elsewhere.

11. Analyses Reported by the Sponsor

The sponsor analysis is reported as a comparison of proportions. Its result is a percentage of 5, with a 95% confidence interval from 1.7 to 9.1 and p < 0.05. The registry does not provide further detail on the precise computation or explain how the percentage relates numerically to the recalculated risk difference.

The unadjusted re-calculation from the posted group summaries gives a risk difference with a negative estimate, an interval below zero, and p = 0.005. The posted outcome counts underlying that calculation are 0 participants with laryngospasm in the lidocaine group and 7 in the placebo group, with 36 participants in each group. The sponsor result and the recalculation are discrepant, so the sponsor’s own analysis takes precedence when describing the trial’s reported analysis.

This precedence does not make the calculation details clearer or remove the discrepancy. It means that the sponsor analysis should be identified as the trial’s reported analysis rather than replaced by a simplified re-calculation. The recalculation is best treated as a separate, unadjusted comparison based on the posted summary statistics. The record does not report why the results differ, whether distinct methods account for the difference, or which precise calculation choices were used in each analysis.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and one analysis, but it does not report a complete statistical analysis plan or a multiplicity strategy. It is therefore not possible to determine from the record whether other comparisons or analyses were planned, conducted, or considered by the investigators. No secondary outcomes are posted in the record.

In general, multiplicity matters when several hypotheses are tested: the chance of at least one result appearing statistically unusual can increase as the number of tests grows. A prespecified strategy can define which outcome is primary and whether any adjustment is needed. The record’s single listed outcome and analysis do not by themselves establish that no other testing occurred or that no multiplicity issue exists.

The registry reports enrollment of 134, but the primary outcome groups each contain 36 participants. It does not provide a participant-flow description that explains this relationship. The analysis population is not reported in the registry record, and the record does not state whether the analysis followed an intention-to-treat principle, used a per-protocol population, or applied another definition.

Missing-data handling is also not reported in the registry record. The posted counts do not establish whether outcome information was available for everyone enrolled or randomized, whether any participants had incomplete follow-up, or how missing observations were treated. The time frame is stated as within the first 15 minutes post-dose, but the record does not describe the procedure for collecting or adjudicating the outcome.

These omissions affect interpretation of both the point estimate and its uncertainty. They do not show that data were missing or that analyses were conducted improperly; they mean that the registry record does not supply the information needed to assess those possibilities. The discrepancy between the sponsor analysis and the recalculation adds a further reason to distinguish the reported analysis from the simple unadjusted re-calculation.

13. 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 posted serious adverse event figures show 0 serious adverse events among the 36 participants at risk in the lidocaine group and 0 among the 36 participants at risk in the placebo group. The registry lists no serious adverse event terms. Death counts are not reported in the registry record.

For other, non-serious adverse events, the record lists 0 affected participants in the lidocaine group and 7 in the placebo group, with 36 at risk in each group. These figures are separate from the serious adverse event counts and should not be combined with them or described as serious events.

Zero recorded serious adverse events in the posted groups does not establish that no serious events occurred outside those groups or that either intervention was free of safety concerns. The trial was terminated by a data monitoring committee due to safety concerns, but the registry record does not report the nature of those concerns or explain their relationship to the adverse-event figures. The event counts should therefore be read as the adverse-event information posted for the stated groups, not as a complete account of the committee’s safety assessment.

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

The registry results show different observed counts for the primary endpoint: 0 participants with laryngospasm in the lidocaine group and 7 in the placebo group. Each outcome group is reported as containing 36 participants. The unadjusted recalculation has a negative risk-difference estimate, an interval below zero, and p = 0.005. The sponsor separately reports a comparison-of-proportions result of 5, with a 95% confidence interval from 1.7 to 9.1 and p < 0.05; because the two analyses are discrepant, the sponsor’s analysis takes precedence as the trial’s own reported analysis.

These results describe the recorded endpoint in this trial. They do not establish that the observed group difference was caused by the intervention, nor do they show that the same pattern would occur in a different population or setting. A confidence interval and p-value characterize statistical uncertainty under their methods; they do not account for every uncertainty in study conduct or reporting.

The outcome window is within the first 15 minutes post-dose. The result therefore addresses the endpoint as recorded in that window, not longer-term outcomes or other clinical measures. The registry’s grade descriptions range from no laryngospasm through stridor or partial laryngospasm, complete laryngospasm, and cyanosis, but details about classification and assessment are not reported.

The record also states that the trial was terminated by a data monitoring committee due to safety concerns. It does not provide enough information to connect the termination decision to the primary outcome or the adverse-event counts. No causal interpretation of the committee’s decision is warranted from the posted information alone.

Enrollment is listed as 134, whereas the posted outcome groups each have 36 participants. The registry does not explain this difference or define the analysis population. Missing-data procedures, participant flow, and the trial’s sample-size justification are not reported. These limitations prevent a full assessment of how the observed comparison relates to all enrolled participants and how broadly it can be interpreted.

15. Why This Trial Matters Statistically

This trial is statistically notable because the endpoint is a participant count and one group has no recorded events. In general, sparse binary data can make estimates and confidence intervals sensitive to the statistical method chosen. That issue is especially relevant when comparing methods or attempting to reproduce a reported analysis from limited summary information.

The registry presents both a sponsor analysis and an unadjusted recalculation, and the results are discrepant. This makes the distinction between a sponsor-reported analysis and a simple re-calculation important. The sponsor’s own analysis takes precedence as the trial’s reported result, while the recalculation can describe what follows from the posted summary statistics under its stated comparison. Neither should be silently substituted for the other.

The record also illustrates why outcome counts, enrollment, and analysis populations should be kept distinct. Enrollment is listed as 134, while the primary endpoint comparison reports 36 participants in each group. Without participant flow or an analysis-population definition, readers cannot determine how those figures are related. This limits evaluation of potential selection and missing-data issues.

Finally, statistical interpretation has to retain the trial’s termination context. The registry states that a data monitoring committee terminated the trial due to safety concerns but does not give further detail. The posted endpoint and adverse-event counts do not explain that decision. Keeping those details separate avoids drawing a safety conclusion from the outcome comparison alone.

16. 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 of interpretation arise from the registry record. The enrollment figure is 134, but the posted outcome comparison includes groups of 36 participants each. No participant-flow account or explanation of this difference is reported. The record also does not define the analysis population, describe missing-data handling, or state whether every randomized participant was included in the analysis.

The trial status is terminated, and the primary outcome population description says termination followed safety concerns identified by a data monitoring committee. The registry does not report the committee’s rationale, stopping criteria, or the timing and effect of the decision on outcome collection. It is not possible to determine how termination affected the posted analysis.

The sponsor analysis and the recalculated unadjusted comparison are discrepant. The registry gives limited information about the computation behind the sponsor’s comparison of proportions, and it does not explain the source of the discrepancy. The sponsor analysis takes precedence as the trial’s own reported analysis, but the difference still limits independent interpretation.

Further endpoint details are not reported: the record does not explain the exact classification rule for the participant count, how outcome assessments were made, or whether events were adjudicated. The trial’s sample-size justification and full statistical analysis plan are also not reported. The listed one outcome and one analysis do not establish whether other analyses were planned or conducted. These gaps do not prove that a particular bias occurred; they restrict what can be concluded from the registry record.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: The Effect of Intravenous Lidocaine on Post-extubation Laryngospasm — NCT01445847.
• Registry record last updated 2017-05-22; status last verified 2017-04.
• Results first posted 2012-07-12.
• 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.

20. Record Summary

The registry record describes a randomized, quadruple-masked, parallel-group trial of intravenous lidocaine versus placebo for postoperative laryngospasm. Enrollment is listed as 134, and the study status is terminated. The recorded primary outcome is the number of participants with laryngospasm within the first 15 minutes post-dose.

The posted outcome counts are 0 in the lidocaine group and 7 in the placebo group, with 36 participants reported in each group. The sponsor reports a comparison-of-proportions result of 5, with a 95% confidence interval from 1.7 to 9.1 and p < 0.05. The recalculated unadjusted comparison is discrepant, so the sponsor’s analysis takes precedence as the trial’s own reported analysis.

The registry says the trial was terminated by a data monitoring committee due to safety concerns, without further detail. It does not report a participant-flow account, analysis-population definition, missing-data approach, or sample-size justification. Those gaps limit interpretation of the posted comparison.