Comparing Ketamine and Morphine in the Treatment of Acute Fracture Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing Ketamine and Morphine in the Treatment of Acute Fracture Pain (NCT02430818), a randomized na study. The primary outcome is Pain Treatment-VAS (Visual Analog Scale).

2. Clinical Question

The clinical rationale in the registry is that opioid medications, including morphine, can have serious side effects, while ketamine is another medication used in emergency departments and can be given at a lower dose for pain control. The stated research question focuses on ketamine alone compared with morphine, rather than ketamine given together with an opioid. The registry’s purpose statement includes both pain relief and the frequency of serious side effects. These are related but distinct questions: pain scores describe a symptom outcome, while adverse-event counts describe recorded harms. The available results should therefore be read as separate descriptive summaries, not as a single overall comparison of benefit and harm.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group study comparing ketamine with morphine. Random allocation is intended to reduce systematic differences between groups at the point of assignment. Masking is intended to limit the influence of treatment knowledge on care, outcome assessment, or reporting. The record identifies the masking level as quadruple, but does not state which roles were masked or how masking was maintained. It identifies a parallel design, meaning participants were assigned to one treatment arm rather than being described as receiving both treatments in sequence.

The study was sponsored by Washington University School of Medicine. Its recorded start was 2015-04 and primary completion was 2017-09. The status is TERMINATED. The reason for termination, its timing relative to the planned study course, and any effect of termination on recruitment or follow-up are not reported in the registry record. The phase is listed as NA.

Enrollment is reported as 13. The arm-level pain outcome summaries report 6 for ketamine and 4 for morphine; the adverse-event summaries list 7 and 6 participants at risk, respectively. These are endpoint-specific counts as recorded, and should not be combined or treated as interchangeable. The record does not explain why the denominators differ across outcome summaries. It also does not report participant flow, the number assigned to each arm at randomization, treatment adherence, protocol deviations, or the number completing each assessment.

The intervention descriptions specify intravenous ketamine at 0.4 mg/kg, capped at 40 mg, and intravenous morphine at 0.1 mg/kg, capped at 10 mg. Details such as administration rate, any repeat dosing, other permitted pain treatments, and the procedures used to manage incomplete or interrupted treatment are not reported in the registry record. The record identifies acute pain and fractures as conditions, and long bone fractures in the official title and study description. It does not provide further eligibility criteria or baseline clinical characteristics.

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 Pain Treatment-VAS (Visual Analog Scale), measured over At 0 minutes and 60 minutes.

The primary outcome is titled Pain Treatment-VAS (Visual Analog Scale). The registry describes a straight line from 0 to 10 inches, with 0 representing no pain and 10 representing the worst pain. It says there are no units on the scale beyond the position marked on the line. Such a scale is used to turn a person’s subjective pain rating into an outcome that can be recorded and compared over time or between treatment groups. The score remains a patient-reported measure, not an objective measure of injury or tissue damage.

The timeframe is recorded as 0 minutes and 60 minutes. The outcome description says assessments occurred at 0, 15, and 60 minutes, but also says the VAS was scored only at 60 minutes. It characterizes the outcome as change in pain. However, the record does not provide baseline scores or an explicit change calculation, so the relationship between the stated change outcome and the arm-level values is not clear from the registry record.

The outcome parameter is listed as a median, with standard deviation as its dispersion measure. The arm summaries give a value of 4.0 for ketamine and 4.0 for morphine, with standard deviations of 1.3 and 1.8, respectively. The registry does not provide confidence intervals or a statistical test for this endpoint. The summaries alone do not establish whether the groups differ or how precisely any difference is estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to treatment groups using a chance-based process. In general, this can help prevent treatment assignment from being systematically linked to measured or unmeasured participant characteristics. It does not guarantee that groups will look alike in every respect, particularly in a small study. The registry identifies random allocation, but does not report the sequence-generation method, concealment procedures, or whether assignment was balanced in practice.

Masking is used to limit the influence of knowledge about treatment assignment. In general, knowledge of treatment can affect participant expectations, clinical decisions, outcome assessment, or the way events are reported. The registry identifies quadruple masking, but does not define the masked roles or describe how treatment identity was concealed. The designation alone cannot establish how successfully masking was maintained.

What do the pain summaries describe?

A median is the middle value when observations are ordered. It can be useful for describing a distribution without relying on the arithmetic mean, especially when values are skewed or affected by extreme observations. A standard deviation describes how spread out observations are around their mean. The record lists the primary outcome parameter as median and its dispersion as standard deviation. Because the median and standard deviation describe different aspects of a distribution, they do not by themselves provide a standard error or confidence interval for a median difference. The record does not explain this reporting choice or provide the underlying participant-level scores.

In general, a confidence interval expresses a range of values compatible with the data and the statistical model used to calculate it. Its width conveys precision: wider intervals indicate less precise estimates, while narrower intervals indicate greater precision. The registry does not report an interval for the pain outcome or for a between-arm contrast. Readers therefore cannot assess the precision of a comparative estimate from the record. A p-value, if reported, would address compatibility with a specified null model; it would not by itself indicate the size, clinical importance, or precision of a treatment effect. No p-value is reported for the primary comparison.

Why does the outcome definition matter?

The outcome is described as change in VAS pain, but the record also says scoring occurred at 60 minutes and gives a timeframe of 0 minutes and 60 minutes. A change measure requires a defined reference value and a clear calculation. A single score at 60 minutes answers a different descriptive question from a change between baseline and 60 minutes. The registry does not provide enough detail to resolve this distinction, and it does not give baseline values. This limits the interpretation of the posted arm summaries.

In general, a comparison of change scores and a comparison of scores at a follow-up time can yield different estimates, particularly if baseline values differ. An adjusted analysis may account for baseline measurements, but the record does not report whether an adjusted model was used. It also does not report the prespecified primary analysis, the model, assumptions, or method for handling repeated assessments. The mention of assessment at 15 minutes does not mean that a 15-minute outcome result is available; the registry says the VAS was scored at 60 minutes.

What can the planning illustration tell readers?

In general, a sample-size calculation uses assumptions about the effect to detect, variability, significance level, power, allocation, and statistical method. The registry’s planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. This is a planning exercise, not a description of the trial’s original design justification. The record does not report the trial’s own sample-size justification or its planned target enrollment.

Such a planning illustration should not be called observed power. Observed power is not a substitute for an effect estimate and its uncertainty; calculations based on an observed effect largely restate information from the observed data. The registry explicitly characterizes the illustration as not the trial’s own design. Its assumptions cannot establish that the study was adequately sized or explain why enrollment and termination took the recorded course. The record does not specify the particular illustrated fractions or report a trial-specific power calculation.

Over-dispersion is a general issue in some count-data models: observed variability exceeds what a simpler model assumes. Accounting for it can change standard errors and confidence intervals. The registry record does not report a count-data model or any analysis of over-dispersion. For the adverse-event results, the listed counts are descriptive and do not require readers to infer an unreported model.

Finally, an analysis plan helps define which outcomes, comparisons, populations, and methods were selected before results were known. It can also explain how multiplicity, missing observations, and deviations from the planned analysis were handled. The registry lists no analyses. It does not report a prespecified statistical analysis plan, an interim analysis, or the methods used to estimate treatment effects. Those omissions mean that a reader cannot verify whether the posted summaries correspond to a planned analysis or determine how analytic choices might affect interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, including the primary VAS outcome, and identifies two secondary outcomes: the number of participants with adverse effects and whether a participant would consider using the assigned drug for pain relief in the future. It does not report a multiplicity plan describing how several outcomes or comparisons were handled. In general, testing many outcomes can increase the chance of finding an apparently notable result by chance. No claim about multiplicity adjustment can be made from this record.

The analysis count is recorded as 0. The registry record does not report a statistical analysis plan, analysis populations, the primary comparison method, or whether any interim analyses took place. It does not identify an intention-to-treat, per-protocol, or other analysis set. The outcome denominators differ from the adverse-event denominators, but the record does not explain the difference. It does not describe missing-data patterns, reasons for missing outcomes, or any method used to address missingness.

In general, missing-data methods rely on assumptions about why observations are missing. Without counts and reasons for missingness, readers cannot assess whether the available outcome summaries represent the randomized groups or whether missing observations could affect interpretation. The registry also does not report the results for the secondary outcome about future willingness to use the assigned drug. That outcome is listed, but its results and analysis are not available in the record. No inference about the result of that outcome is warranted.

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 adverse-event record lists 7 participants at risk in the ketamine arm and 6 in the morphine arm. It records 0 serious adverse events in each arm, 1 other adverse effect in each arm, and 0 deaths in each arm. These are counts, not comparative estimates. No rates, confidence intervals, or statistical comparison are reported, and no serious adverse-event terms are listed.

The at-risk counts are specific to the adverse-event summary and should not be substituted for the arm-level pain-outcome counts. The record does not explain the differing denominators or give details about event types, timing, severity definitions, or how events were collected. In general, a count of zero in a small observed group does not establish that an event cannot occur or that treatments have the same safety profile. It means only that no such event was recorded in the listed group during the period covered by this summary.

The registry’s stated purpose includes looking at serious side effects, but the posted counts alone cannot establish comparative safety. The record does not report a formal safety analysis or enough follow-up detail to characterize the chance of uncommon harms. These figures should be read as descriptive adverse-event reporting, not as a guarantee of safety or as a basis for treatment decisions.

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

The registry record describes a randomized comparison of ketamine and morphine for acute pain associated with long bone fractures. The primary outcome uses a VAS, with the posted arm-level median listed as 4.0 for both treatments. The record also lists standard deviations of 1.3 for ketamine and 1.8 for morphine. These figures give descriptive information about the recorded outcome, but they do not provide a treatment-effect estimate or its uncertainty.

The registry’s description of the endpoint leaves an important interpretive question unresolved: it refers to change in pain, gives assessment times of 0 minutes and 60 minutes, and states that the VAS was scored at 60 minutes. No baseline values or change calculation are reported. Therefore, the arm summaries cannot be confidently interpreted as a specific change from baseline or as a 60-minute score based on the record alone.

The record does not report a p-value, confidence interval, or comparative model. It cannot establish that the treatments differ, that they are equivalent, or that they have the same effect. Likewise, the absence of a reported comparative result is not proof that no difference exists. The adverse-event counts are also descriptive and do not establish equivalence or superiority in safety.

Enrollment is reported as 13, and the trial status is TERMINATED. The record does not explain the termination or provide participant flow, missing-data details, or the analysis population. Those limitations make it difficult to know how representative the posted summaries are of all participants enrolled or assigned to treatment. They also prevent assessment of the reasons that the outcome counts differ from the adverse-event at-risk counts.

These results should therefore be understood as limited registry summaries from this study, not as a definitive answer to the clinical question. They do not justify a treatment recommendation. The record also does not report enough detail to generalize the findings to other patient groups, settings, dosing practices, or pain outcomes. A fuller interpretation would require the planned analysis, clear outcome definitions, participant flow, uncertainty estimates, and a detailed account of study termination and missing observations.

13. Why This Trial Matters Statistically

This study raises several statistical issues that commonly arise when interpreting small clinical trials. Randomization and masking are important design features, but they do not eliminate uncertainty in the results. When the recorded outcome counts are limited, descriptive summaries can be sensitive to the observations included, and estimates may be imprecise. In this record, there is no confidence interval for the primary outcome or reported between-arm estimate with which to assess that precision.

Clear endpoint definitions are equally important. A score at a follow-up assessment and a change from baseline answer different questions. The registry describes pain change but also says that VAS was scored at 60 minutes, without providing baseline values or a calculation of change. This makes the estimand—the exact treatment effect the analysis is intended to estimate—unclear in the posted record. A reader cannot determine whether the listed medians represent follow-up scores or changes.

The differing arm denominators for pain outcomes and adverse events also illustrate why participant flow and analysis-population descriptions matter. Without those details, readers cannot tell whether outcome summaries use the same participants, whether observations are missing, or why the counts differ. Missing-data handling can affect estimates, particularly when the reasons for missing observations relate to outcome or treatment experience.

Finally, the registry labels the trial TERMINATED and reports no analyses. A planning illustration based on observed effects cannot replace an original sample-size justification or a prespecified analysis. It is not observed power and cannot resolve whether a study’s estimates are sufficiently precise. The record is therefore statistically important less as a settled comparison than as an example of how design labels, endpoint descriptions, denominators, analysis plans, and uncertainty estimates all contribute to sound interpretation.

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.

The registry record leaves material details about conduct and reporting unspecified. It does not report the reason for the TERMINATED status, whether termination affected recruitment or follow-up, or whether outcome collection was complete. Participant flow, eligibility criteria, baseline characteristics, adherence, and protocol deviations are not reported. These omissions limit assessment of how the enrolled participants relate to the intended population and whether the observed groups remained comparable after randomization.

The primary endpoint description is internally difficult to interpret: it calls the outcome change in pain, refers to assessment at 0 minutes and 60 minutes, and says VAS was scored at 60 minutes after assessments at 0, 15, and 60 minutes. Baseline scores, a change calculation, and a clear description of the arm-level values are not reported. The record also lists median as the outcome parameter and standard deviation as the dispersion measure without explaining the summary choice or providing individual observations.

No inferential analysis is reported for the primary endpoint. The record contains no treatment-effect estimate, confidence interval, p-value, model specification, or account of assumptions. It does not identify analysis populations or missing-data methods. The primary-outcome counts differ from the adverse-event at-risk counts, and the reason is not reported. Results for the listed future-use secondary outcome are not reported. The adverse-event record gives counts but limited detail about event definitions, collection, and follow-up. These gaps restrict interpretation and prevent a robust assessment of the precision, completeness, and generalizability of the posted results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparing Ketamine and Morphine in the Treatment of Acute Fracture Pain — NCT02430818.
• Registry record last updated 2019-05-22; status last verified 2019-04.
• Results first posted 2019-05-22.
• 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 a randomized, quadruple-masked, parallel study sponsored by Washington University School of Medicine. It compares intravenous ketamine, specified as 0.4 mg/kg with a 40 mg maximum, with intravenous morphine, specified as 0.1 mg/kg with a 10 mg maximum, for acute pain associated with long bone fractures. Enrollment is reported as 13; the recorded status is TERMINATED.

The primary outcome is Pain Treatment-VAS, described on a scale from 0 to 10. The arm summaries list a median of 4.0 for ketamine and 4.0 for morphine, with standard deviations of 1.3 and 1.8. The registry does not report a comparative analysis, confidence interval, or p-value, and does not resolve whether the posted values represent a follow-up score or change from baseline.

Adverse-event counts are descriptive: the record lists 0 serious adverse events, 1 other adverse effect, and 0 deaths in each arm. It does not report the reason for termination, a statistical analysis plan, missing-data methods, or analysis populations. The posted information therefore supports a limited description of the recorded outcomes, not a definitive comparative conclusion.