Ketamine For Acute Treatment of Pain in Emergency Department: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine For Acute Treatment of Pain in Emergency Department (NCT02306759), a randomized phase 4 study. The primary outcome is Change From Baseline of Pain as Described by Numeric Rating Scale (NRS) [Minimum:0, Maximum 10] at 15 Minutes.

2. Clinical Question

3. Trial Design

NCT02306759 is a completed Phase 4, randomized, quadruple-masked, parallel-group trial sponsored by The Brooklyn Hospital Center. The registry lists enrollment as 60. The recorded start was 2015-01 and primary completion was 2015-11. These record details describe the trial's registration and design; they do not themselves establish how faithfully masking was maintained or whether every planned procedure was carried out.

The two arms differ by the infusion administered: ketamine in the treatment arm and normal saline in the placebo arm. Both arm descriptions include morphine available as needed at designated intervals. This makes the core comparison an add-on comparison of ketamine versus placebo in the context of the described morphine regimen. The study's brief summary states that the investigators aimed to compare safety and efficacy for acute generalized pain in the emergency department and were interested in ketamine as an alternative option to opioids. However, because morphine was part of both arm descriptions, the actual randomized comparison should not be described as ketamine replacing morphine.

The registry reports five outcome measures, including the primary pain-change measure and secondary outcomes relating to adverse events, satisfaction, rescue analgesia, and emergency-department length of stay. Numerical summaries are posted for the primary outcome, satisfaction, length of stay, and adverse events. The registry indicates that values are missing or not estimable for a two-arm comparison for another endpoint. The registry record does not report the specific randomization procedure, allocation concealment method, masking details for each role, or the designated intervals for morphine. It also does not report a protocol or a statistical analysis plan in the information summarized in the record.

The distinction between design and results is important. Randomization and masking are design features intended to support a fair comparison, but they do not guarantee that estimates are unbiased or precise. The small group summaries and lack of a posted primary comparative analysis mean that the main interpretive emphasis must remain on what was actually recorded: arm-level outcome summaries, their spread, and the incomplete reporting of comparative inference.

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

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 Change From Baseline of Pain as Described by Numeric Rating Scale (NRS) [Minimum:0, Maximum 10] at 15 Minutes, measured over 15 minutes after administration of study intervention.

The primary endpoint is the change from baseline in pain as described by the Numeric Rating Scale at 15 minutes after administration of the study intervention. The scale runs from 0 to 10. The registry identifies the outcome as a median with inter-quartile range, so the central value is the middle-ranked observed change in each arm, while the inter-quartile range describes the span of the middle half of observations. This presentation is appropriate for reporting a distribution through its centre and central spread without relying on a mean and standard deviation.

The endpoint focuses on an early assessment after the infusion. Pain ratings are a direct patient-reported measure of the symptom targeted by the intervention, while the fixed assessment time makes the two arms comparable at the same stated point. The record says higher values indicate better outcomes and lower values indicate worse outcomes for this change measure. That direction should be retained when interpreting the posted medians, rather than assuming that the direction used for a raw pain score also applies to a change score.

In the treatment arm, the median change was 3.5, with an inter-quartile range from 1.0 to 7.3. In the placebo arm, the median was 6.0, with an inter-quartile range from 4.0 to 9.0. These are descriptive summaries. The registry does not post a comparative estimate or uncertainty interval for the primary endpoint, nor does it identify the analysis population or explain how baseline and follow-up observations were handled. The endpoint therefore indicates what was summarized, but the record does not provide enough inferential detail to quantify the comparative effect on this outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry uses different summaries for outcomes with different statistical forms. The primary pain-change outcome is represented by a median and inter-quartile range. The satisfaction and length-of-stay outcomes are represented by means and standard deviations. These summaries answer different descriptive questions, so they should not be treated as interchangeable.

What does a median and inter-quartile range describe?

A median is the central observation when values are ordered. It is less affected than a mean by unusually high or low observations, which can make it useful when a distribution is skewed or when a typical value is more informative than an arithmetic average. The inter-quartile range spans the middle half of the observations. It describes central spread, but it is not a confidence interval for the median and does not directly indicate the precision of a between-arm effect estimate. The registry reports the primary endpoint this way, but does not report a confidence interval for the comparative effect.

For the primary outcome, the medians are 3.5 in the treatment arm and 6.0 in the placebo arm. The inter-quartile ranges are 1.0 to 7.3 and 4.0 to 9.0, respectively. Those statistics describe the observed group distributions in the posted record. A comparative analysis of medians would require an appropriate method and an explicit estimate of uncertainty. The registry does not report such an analysis, so one should not infer a formal test from the arm summaries alone.

What do means and standard deviations describe?

A mean is the arithmetic average. A standard deviation describes how dispersed individual values are around that average. The mean can be sensitive to extreme values, while the standard deviation reflects the scale of variation in the observations. Neither statistic alone gives the uncertainty of the difference between group means; that uncertainty also depends on sample information and the analysis method. A confidence interval for a difference gives a range of effect values compatible with the data under the assumptions of the analysis. It is not a range containing a fixed proportion of individual observations.

For satisfaction and length of stay, the posted arm summaries are means and standard deviations. The accompanying unadjusted calculations compare these means and provide confidence intervals and p-values. They are recalculations from posted summary statistics, not reported sponsor analyses. The satisfaction comparison has p < 0.001, while the length-of-stay comparison has p = 0.623. A p-value describes how incompatible the observed data are with a specified null model under the calculation's assumptions; it is not the probability that the null hypothesis is true, nor does it measure clinical importance. A small p-value does not remove the need to consider the estimate, its uncertainty, the endpoint's role, and multiplicity.

How should confidence intervals be read?

A confidence interval combines an estimated effect with its precision. A narrower interval conveys greater precision under the method's assumptions, while a wider interval leaves more uncertainty about the effect's magnitude and direction. For a difference, an interval spanning zero is compatible with no difference as well as with differences in either direction. The interval for the recalculated length-of-stay comparison spans zero, so the posted summary data do not sharply distinguish between those possibilities. The satisfaction interval is wholly above zero, but it remains an unadjusted secondary calculation and must be interpreted in that context.

Confidence intervals also depend on the model and assumptions used to calculate them. The registry does not report a primary interval or describe a model for the primary endpoint. The unadjusted secondary calculations use the posted means and standard deviations and should not be mistaken for adjusted estimates or for the sponsor's own analysis. No discrepancy is flagged for these recalculations, but that does not make them prespecified or multiplicity-adjusted.

Why do the planning illustrations differ from observed results?

The sample-size illustrations are planning exercises based on the observed effect, not the trial's own design justification and not observed power. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The rows describe planning for 100%, 75%, or 50% of the observed effect, and the results are expressed as participants per arm for 80% or 90% power. Such calculations help illustrate how sample size changes when the target effect is smaller or larger, but they do not establish whether the original trial was adequately powered. The registry record does not report the original sample-size justification, target effect, or intended power.

Planning based on an observed effect is especially uncertain when the observed estimate comes from a small study, because estimates may fluctuate and can overstate or understate the effect that would be seen in a new study. The illustrations are not a guarantee of future power and do not repair missing outcome data or missing analyses. They should be treated as hypothetical design guidance under stated assumptions rather than as evidence about the reliability of the trial's result.

What cannot be assessed from the posted methods?

The registry does not report the primary statistical test, an adjusted model, the analysis population, missing-data procedures, handling of protocol deviations, or interim analyses. It does not report whether randomization was stratified or how the allocation sequence was generated. Without these details, readers cannot verify whether the analysis followed a prespecified plan or evaluate the sensitivity of results to alternative assumptions. General statistical considerations, such as the need to account for skew or repeated measurements when relevant, cannot be assigned to this trial without those details. The appropriate conclusion is therefore limited to the posted summaries and the explicitly identified unadjusted calculations.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. This matters because several outcomes are listed, including the primary pain-change outcome and secondary measures addressing satisfaction, rescue analgesia, length of stay, and adverse events. When several outcomes are examined, interpreting each unadjusted p-value as though it were the only test can overstate the strength of evidence. Adjustment methods, hierarchical testing, or a clearly designated confirmatory endpoint can address this issue, but the record does not describe any such approach. It would therefore be inappropriate to assume that the posted secondary comparisons were adjusted or that they followed a prespecified testing order.

The primary outcome has descriptive arm summaries, but no posted comparative confidence interval or p-value. The registry records no reported analyses. The simple unadjusted recalculations for the posted continuous secondary summaries are not a substitute for the missing primary analysis and do not establish that they were part of the original statistical plan. No sponsor-reported statistical analysis is listed for these secondary endpoints.

Missing-data handling is not reported in the registry record. The primary outcome's population field is blank, and the record does not explain whether every randomized participant contributed a baseline and follow-up pain rating, how incomplete ratings were treated, or whether any imputation was used. It also does not specify whether analyses followed intention-to-treat, per-protocol, or another population definition. Arm-level sample counts in outcome summaries do not, by themselves, answer these questions or establish why observations may be absent.

The record does not report interim analyses, stopping rules, protocol deviations, or sensitivity analyses. These omissions limit assessment of whether the posted results are robust to alternative analysis choices. They do not establish that such procedures were absent; they mean they are not reported in the registry record. In the absence of those details, interpretation should remain focused on the posted data, with uncertainty about analysis populations, missingness, and multiplicity kept explicit.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists no serious adverse events in either arm: the serious-event count is 0 among 30 participants at risk in the treatment arm and 0 among 30 at risk in the placebo arm. It also records 0 deaths in both arms. For other adverse events, the posted counts are 2 among 30 at risk in the treatment arm and 4 among 30 at risk in the placebo arm. These are observed counts in the registry record, not proof that no additional events occurred outside the recorded reporting period or definitions.

The absence of reported serious events in these groups should not be interpreted as evidence that serious harm is impossible. Counts from a limited study can provide only limited information about uncommon events, and the record does not provide event terms for the serious-event category. The list of top serious-event terms is empty. The registry also does not provide detailed definitions, severity grading, attribution, or follow-up procedures in the information recorded.

The other-event counts are descriptive. They do not establish that the observed numerical difference between arms reflects a reliable treatment-related difference. A formal safety comparison would need to account for event definitions, exposure, observation time, and the analysis plan; those details are not reported in the registry record. The appropriate reading is that the record reports no serious events or deaths and records the stated counts of other adverse events in each arm, while the precision and completeness of safety comparisons remain unclear.

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

The registry record shows that NCT02306759 was a randomized, quadruple-masked, parallel-group study comparing ketamine plus morphine with placebo plus morphine for acute pain in an emergency department. It reports arm-level summaries for change in pain at 15 minutes and selected secondary outcomes. Those details describe the comparison and the posted observations; they do not, on their own, establish that one approach is superior or equivalent.

For the primary outcome, the treatment-arm median change is numerically lower than the placebo-arm median, while the registry defines higher values as better outcomes. But a median alone is not a comparative effect estimate, and the record provides no primary confidence interval or test. The observed summaries therefore should be presented with their direction and spread, while leaving the uncertainty about the between-arm difference unresolved. Neither a claim of benefit nor a claim of no effect follows from these summaries alone.

The secondary recalculations offer estimates for satisfaction and emergency-department length of stay, but they are unadjusted calculations based on the posted summary statistics. They are not identified as sponsor analyses and may be affected by multiple testing. They can help readers understand the range and direction of the posted data, but they cannot substitute for a reported primary analysis or justify a broad conclusion about efficacy. A non-significant result in one secondary comparison is not evidence that the groups are equivalent; an apparently notable result on another does not establish a definitive treatment effect.

The safety record reports no serious adverse events or deaths in either arm and provides counts for other adverse events. These data are reassuring only in the narrow descriptive sense that no such serious events were recorded in the registry result; the information does not show that risk is absent or allow a precise assessment of rare harms.

Overall, the record is informative about the trial's question, design, and available summaries, but incomplete for determining the size and precision of the primary comparative effect. Missing analysis details, absent primary inferential results, and limited reporting of populations and missing data constrain what can be concluded. This is a statistical interpretation of the registry record, not a recommendation about clinical care.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it demonstrates the difference between a randomized design and a fully interpretable reported comparison. Random assignment and masking are important design features, but a reader also needs an outcome definition, arm-level data, a comparative estimate, and an account of uncertainty. Here, the primary endpoint is described and summarized by arm, yet the record does not provide a primary between-arm estimate or test. The design label cannot fill that inferential gap.

The choice of summary statistic also matters. Pain change is presented as a median and inter-quartile range, whereas satisfaction and length of stay are presented as means and standard deviations. Each format describes the observed data in a different way. A reader should not infer a primary treatment effect by informally comparing group medians, nor assume that secondary mean-based calculations answer the same question.

The record also illustrates why statistical significance is not a complete interpretation. A secondary recalculation can have a small p-value and still be exploratory, particularly when the analysis is not reported by the sponsor and the multiplicity plan is unknown. Conversely, a broad confidence interval around a secondary estimate can leave substantial uncertainty even when its point estimate has a direction. Estimates, intervals, endpoint roles, and analysis provenance all belong in the interpretation.

Finally, planning illustrations derived from observed effects are not evidence of observed power and cannot retrospectively justify the trial's sample size. They are hypothetical tools whose results depend on assumptions. The original sample-size rationale is not reported in the registry record. These distinctions help clinical researchers separate design intent, descriptive results, recalculated inference, and confirmatory evidence when evaluating a clinical trial record.

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 restrict interpretation. The main one is the absence of a posted comparative analysis for the primary pain-change endpoint. Although each arm has a median and inter-quartile range, there is no primary effect estimate, confidence interval, or p-value. The record also does not identify the primary analysis population, so it is unclear which participants contributed to that endpoint and how incomplete observations were handled.

The primary outcome is assessed 15 minutes after the intervention. This is a defined early time point, but the record does not provide additional primary pain measurements over time or a reported analysis of change trajectories. The registry lists other outcomes, yet a numerical two-arm comparison is missing or not estimable for one endpoint. This makes the overall pattern across pain, rescue medication, and other outcomes difficult to evaluate comprehensively.

The secondary numerical comparisons available for satisfaction and length of stay are unadjusted recalculations from summary statistics, not sponsor-reported analyses. The multiplicity strategy and analysis plan are not reported. Their inferential results should therefore be treated cautiously, and they cannot confirm the primary finding. The registry also does not explain the reasons for the missing or non-estimable comparison, provide sensitivity analyses, or report methods for dealing with missing data.

The short summary describes an emergency-department population with acute generalized pain, but detailed eligibility criteria and participant characteristics are not reported in the registry record. The record does not provide enough information to assess how broadly the observed results might apply to other patient groups or care settings. Further limitations include unreported randomization procedures, allocation concealment, detailed masking procedures, morphine administration intervals, and the original sample-size justification. These are reporting gaps, not proof that the procedures were absent. Together they counsel against conclusions stronger than the available summaries support.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ketamine For Acute Treatment of Pain in Emergency Department — NCT02306759.
• Registry record last updated 2017-08-09; status last verified 2017-07.
• Results first posted 2017-06-01.
• 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

NCT02306759, titled Ketamine For Acute Treatment of Pain in Emergency Department, is recorded as a completed Phase 4 randomized, quadruple-masked, parallel-group trial sponsored by The Brooklyn Hospital Center. The registry lists enrollment as 60 and records a start of 2015-01 and primary completion of 2015-11. The comparison was ketamine plus morphine versus placebo plus morphine for acute pain in an emergency department.

The primary endpoint was change in Numeric Rating Scale pain at 15 minutes, reported by arm as a median and inter-quartile range. The registry does not post a comparative primary analysis. Secondary summaries include satisfaction and emergency-department length of stay, with unadjusted recalculations available for those outcomes; one endpoint is recorded as missing or not estimable for a two-arm comparison. The safety record lists no serious adverse events or deaths and reports other adverse-event counts by arm. Statistical analysis details, missing-data methods, and multiplicity handling are not reported in the registry record.