Combination of Magnesium and Lidocaine for the Pretreatment of Pain That is Caused by the Injection of Propofol: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination of Magnesium and Lidocaine for the Pretreatment of Pain That is Caused by the Injection of Propofol (NCT01342510), a randomized phase 4 study. The primary outcome is Percentage of Participants Reporting Pain With Injection of Propofol.

2. Clinical Question

The clinical question is whether the reported frequency of pain differs across the three pretreatment preparations and saline control. The registry describes giving the study drug before 50 mg of propofol, then asking participants a standard question about pain and noting behavioral signs. Pain was rated on a four-point scale ranging from no pain to severe pain. The record does not report a single prespecified pairwise comparison or an overall statistical test for the four arms. It therefore supports a description of the group-specific percentages and their uncertainty, but not a conclusion about a statistically established difference between any particular pair of groups.

3. Trial Design

The registry describes a completed phase 4, randomized, quadruple-masked, parallel-group trial sponsored by the University of Wisconsin, Madison. The listed enrollment is 200. The trial began in 2011-04, and primary completion is recorded as 2012-04. The registry status is completed.

Four groups are described: lidocaine, magnesium, lidocaine/magnesium, and saline control. The active preparations and control were each administered in a 10 cc syringe. The combination arm contained both lidocaine 50 mg and magnesium sulfate 0.25 g (2 mOsmol). The registry record does not specify the method used to generate or conceal the random allocation sequence. It also does not identify which roles were masked, so the meaning of quadruple masking cannot be expanded beyond the registry’s classification.

The design is parallel rather than crossover: participants are assigned to one study arm, and the endpoint is reported separately for each arm. For the primary outcome, the posted group counts are 38.0 for lidocaine, 44.0 for magnesium, 37.0 for lidocaine/magnesium, and 39.0 for control. These outcome counts should be read as the denominators associated with the posted group results; the registry does not explain how they relate to the listed enrollment or describe participant flow.

The brief summary frames the study around the use of magnesium and lidocaine together in a single syringe before propofol. The record also includes the single-agent arms and saline control, which allow the reported pain percentages to be viewed across all four preparations. It does not report additional design details such as eligibility criteria, setting, allocation ratio, or protocol deviations.

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: 200 participants were consented. The participants were distributed between the groups as follows, 39 participants in the control group, 38 in the lidocaine group, 44 in the magnesium group, and 37 in the magnesium/lidocaine group. Participants did not receive study drug if ASA score or peripheral IV inserted was not a 20 gauge.

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 of Participants Reporting Pain With Injection of Propofol, measured over Approximately 10 seconds following administration of propofol..

The primary endpoint is the percentage of participants reporting pain with injection of propofol. Pain was assessed approximately 10 seconds after propofol administration. The registry description says that 50 mg of propofol was injected after the study drug, that participants were asked a standard question about pain, and that behavioral signs were noted.

The assessment used a four-point scale: 0 means no pain; 1 means mild pain, reported only in response to questioning and without behavioral signs; 2 means moderate pain, reported in response to questioning with a behavioral sign, or reported without questioning; and 3 means severe pain, described as a strong vocal or behavioral response. The posted primary outcome is expressed as a percentage reporting pain, rather than as the full distribution across all four scale categories. The registry does not report the number of participants in each severity category or explain in further detail how the scale responses were converted into the reported percentage.

A percentage is useful for describing how common the recorded outcome was in each study arm. It offers a direct group-level summary of the occurrence of reported pain, while the confidence interval conveys uncertainty around that estimate. This endpoint captures a short-term response to propofol injection; it does not, by itself, measure other anesthesia outcomes, longer-term effects, or the overall experience of care.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the posted results can and cannot show. The registry reports a randomized parallel-group design and an endpoint expressed as a percentage in each arm. It does not report a statistical analysis for comparing those percentages. The explanation below distinguishes general statistical principles from the analyses actually documented in the registry record.

What does a confidence interval describe?

In general, a confidence interval expresses uncertainty around an estimate. A narrower interval indicates greater precision under the assumptions of the method used; a wider interval indicates more uncertainty. The posted 95% confidence intervals accompany each group’s pain percentage. They do not directly quantify uncertainty in the difference between a study preparation and saline control. To answer a comparative question, an analysis would ordinarily report a contrast, such as a difference in percentages, together with its confidence interval and an appropriate test or other inferential summary. The registry does not report these comparative quantities.

A confidence interval should not be read as a range containing a fixed proportion of individual outcomes, nor as a guarantee that the true value lies within its endpoints. It is a repeated-sampling statistical construct whose interpretation depends on the method and assumptions used. The registry identifies the intervals as 95% confidence intervals but does not describe their calculation method. The posted estimates can therefore be read with their stated uncertainty, while the exact interval procedure remains not reported in the registry record.

Why are group estimates not the same as treatment contrasts?

Each arm’s percentage describes that arm. A treatment contrast compares two arms directly and accounts for uncertainty in both. Merely noting that percentages differ numerically does not quantify the contrast’s precision. Nor does overlap or non-overlap between separate confidence intervals serve as a substitute for a reported test of the contrast. In general, the direct comparison should be defined in advance, estimated using an appropriate method, and interpreted with its uncertainty. The registry lists four arms but does not report which specific contrasts were planned or analyzed.

What does randomization contribute?

In general, random assignment is intended to make treatment groups comparable with respect to factors measured and unmeasured at baseline, on average. This supports a causal interpretation of a well-conducted trial when allocation, follow-up, outcome measurement, and analysis are also handled appropriately. Randomization does not guarantee identical groups in a particular trial, and it does not resolve missing outcomes or unclear analysis choices. The record classifies the trial as randomized but does not describe sequence generation, allocation concealment, baseline characteristics, or how departures from assigned treatment were handled.

What does masking contribute?

The registry classifies masking as quadruple. In general, masking can reduce the risk that knowledge of assigned treatment influences care, outcome assessment, or reporting. The endpoint includes a participant report and observed behavioral signs, so the roles of participants and assessors could matter to measurement. However, the registry does not specify who was masked, whether masking was maintained, or whether it was assessed. No stronger claim about protection from bias can be made from the classification alone.

Why does endpoint definition matter?

The registry gives a four-point pain scale and describes a question to participants alongside observation of behavior. The reported endpoint is the percentage reporting pain, but the record does not provide the complete scale distribution or further detail on the rule used to classify responses for that percentage. In general, a clear operational definition is important because different rules for combining reported pain and behavioral signs could lead to different summaries. The short assessment timing also means the endpoint addresses pain shortly after propofol injection, not pain or other outcomes over a longer period.

How should planning calculations be understood?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance threshold, power, and allocation. A planning illustration based on an observed effect is not evidence that the completed trial had a specified power, and it is not the trial’s original design justification. The registry record does not report the original sample-size justification or a prospective power calculation. Any planning illustration associated with the posted results should therefore be interpreted as hypothetical rather than as observed power or proof that the trial could detect a particular difference.

The record identifies 200 as the enrollment and reports arm-specific outcome counts, but it does not report an analysis population or an analysis method for the primary endpoint. Without those details and direct contrast estimates, the most defensible statistical reading is descriptive: the registry reports percentages and confidence intervals for each arm, while the comparative statistical evidence remains unreported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and reports no secondary posted outcomes. It also lists no analyses. The record does not report whether multiple comparisons among the four arms were planned, whether any outcome or subgroup analyses were performed, or whether an adjustment for multiple testing was used. Because several possible comparisons could be made among the arms, multiplicity is relevant to interpreting any set of inferential tests. No multiplicity procedure can be identified from the registry record.

Missing-data handling is not reported. The registry does not state how participants with no recorded pain assessment were treated, whether any endpoint observations were excluded, or whether an imputation or sensitivity analysis was used. The primary outcome is accompanied by arm counts, but the record does not give a participant-flow account that explains the relationship between those counts and the listed enrollment of 200. No conclusion about the extent or consequences of missing outcome data can be drawn from the available record.

The analysis population is also not reported. The registry does not say whether the primary endpoint was analyzed according to randomized assignment, treatment received, or another population definition. Nor does it describe protocol deviations or the treatment of participants who did not follow the assigned procedure. These omissions matter because population definitions and missing-data choices can affect the interpretation of group comparisons.

In general, clear reporting of planned comparisons, analysis populations, exclusions, and missing-data methods helps readers judge whether the reported results answer the original question and how robust they are to analysis choices. These elements are not reported in the registry record, so interpretation should remain focused on the posted group-specific estimates rather than an unreported inferential analysis.

11. 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 serious adverse event figures for each arm as 0 affected among 50 at risk: lidocaine, magnesium, lidocaine/magnesium, and control. It lists no serious adverse event terms. These figures indicate that the registry records no affected participants for the serious-event measure in any arm. The record does not provide further details about the event definitions, observation period, or how serious events were collected.

The registry also lists other adverse events: 11 affected among 50 at risk for lidocaine, 25 among 50 for magnesium, 15 among 50 for lidocaine/magnesium, and 18 among 50 for control. These figures are distinct from the serious adverse event figures and should not be interpreted as a measure of severity. The registry does not provide event-level descriptions for these other adverse events, so their nature and clinical importance cannot be characterized from these counts.

A zero serious-event count in the recorded group does not demonstrate that the risk is absent. Safety estimates depend on the number observed, the event definitions, duration of follow-up, and completeness of reporting. The registry provides no deaths figures, and deaths are not reported in the registry record. These safety data should be read as registry counts, not as proof that a preparation is free of harm or as a basis for comparing safety between arms.

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

The results provide a descriptive account of pain reports after propofol injection across four randomized trial arms. The posted percentages range from 29.0% in the lidocaine arm to 57.0% in the magnesium arm, with the combination at 41.0% and saline control at 46.0%. Each estimate has a 95% confidence interval, reflecting uncertainty in the reported group percentage. The figures show variation among the observed arm summaries, but they do not by themselves establish a reliable difference between preparations.

The registry does not report direct comparisons, corresponding confidence intervals for differences, p-values, or a primary analysis method. Therefore, the posted data do not support a firm conclusion that the combination differs from saline, or that it differs from either single-agent arm. A comparison based only on which point estimate is numerically lower would disregard uncertainty and the absence of a reported comparative analysis.

The endpoint is specific: participant-reported pain, assessed approximately 10 seconds after propofol administration, with behavioral signs also noted. It does not answer broader questions about anesthesia quality, other treatment outcomes, or longer-term effects. The record does not report participant eligibility details or demographic characteristics, which limits assessment of how broadly the observed results may apply.

The trial record also leaves important interpretive details unspecified, including how missing endpoint data were handled, the analysis population, and which contrasts were planned. Those gaps do not erase the posted group results, but they constrain conclusions that can be drawn from them. A complete assessment of comparative effects would require clearly reported analyses of the intended contrasts, with uncertainty estimates and enough information to understand participant inclusion and outcome handling.

Accordingly, the result is best understood as a set of arm-specific pain percentages with confidence intervals, not as a definitive ranking of the preparations. It records what the trial registry reports for this short-term endpoint while leaving the inferential comparison and some aspects of implementation and analysis unresolved.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it has four parallel groups addressing a focused measurement question: the percentage reporting pain shortly after propofol injection. Its randomized, quadruple-masked classification describes design features intended, in general, to support fair comparisons and limit bias. The registry also includes both single-agent preparations and their combination, alongside saline control, so the arm-level results can be viewed in the context of several candidate preparations.

The main statistical lesson is the distinction between descriptive estimates and comparative evidence. Group-specific percentages are useful for showing the observed outcome in each arm, and confidence intervals communicate their uncertainty. But those quantities are not substitutes for prespecified contrasts and their uncertainty. Without reported comparisons, readers should avoid treating numerical ordering as a statistical conclusion.

The record also illustrates why completeness of reporting matters. Even when outcome percentages and confidence intervals are available, interpretation depends on details such as analysis populations, endpoint definitions, missing-data handling, and multiplicity. The registry does not report these elements in sufficient detail to establish how the primary result was analyzed or whether a particular pairwise question was the main inferential target.

Finally, the outcome is time-specific and focused on pain following an injection. Its statistical interpretation should stay within that scope. The posted results can help readers understand the observed group-level pattern, but the information in the registry record does not support broader claims about treatment effects or clinical performance.

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 limitations specific to this record constrain interpretation. The registry does not report eligibility criteria, participant characteristics, or the setting in enough detail to assess the representativeness of the participants. It describes the outcome timing and scale, but does not report the full distribution across the pain scale or a detailed rule linking scale responses to the percentage reporting pain.

Although the study is classified as randomized and quadruple-masked, the allocation-generation and concealment procedures are not described, and the masking roles are not identified. The record also does not report baseline characteristics or adherence to assigned preparation. These omissions prevent a detailed assessment of group comparability and the practical implementation of masking.

The posted primary results have arm-specific counts and confidence intervals, but there are no reported between-group estimates or tests. The analysis method, analysis population, missing-data handling, and planned comparisons are not reported in the registry record. The record lists enrollment of 200, while the primary outcome is reported with arm counts; it does not explain participant flow or how those counts relate to enrollment. This limits assessment of completeness and possible selection in the endpoint results.

Safety reporting is also limited: serious adverse event counts are recorded, but serious-event terms and deaths are not reported, and details about definitions and follow-up are absent. Other adverse events are counted without event-level descriptions. These limitations mean the registry figures can be described, but not used to make a complete assessment of comparative safety or to infer that unrecorded events did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combination of Magnesium and Lidocaine for the Pretreatment of Pain That is Caused by the Injection of Propofol — NCT01342510.
• Registry record last updated 2019-05-29; status last verified 2019-05.
• Results first posted 2012-06-25.
• 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.

18. Record Summary

The registry record describes NCT01342510, a completed phase 4 randomized, quadruple-masked, parallel-group trial sponsored by the University of Wisconsin, Madison. Listed enrollment is 200. The trial began in 2011-04, with primary completion in 2012-04. Its four arms were lidocaine, magnesium sulfate, lidocaine/magnesium, and saline control.

The primary outcome was the percentage reporting pain approximately 10 seconds after propofol administration. The posted arm-specific estimates range from 29.0% to 57.0%, each with a 95% confidence interval. The registry does not report comparative analyses, the analysis population, or missing-data methods. Serious adverse events are recorded as 0 affected among 50 at risk in each arm; further serious-event details are not reported. The results are best read as descriptive group summaries rather than a reported test of differences between treatments.