Ketamine for Acute Pain Management After Trauma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine for Acute Pain Management After Trauma (NCT04129086), a randomized phase 4 study. The primary outcome is Average Daily Opioid Use as Measured by the Morphine Milligram Equivalents (MME) Per Day.

2. Clinical Question

3. Trial Design

The KAPT trial was a randomized, single-masked, parallel-group Phase 4 study. Participants were assigned to ketamine plus usual care or usual care alone. The registry lists enrollment as 305. The primary outcome summaries give arm sizes of 144.0 for ketamine plus usual care and 156.0 for usual care; these are the denominators associated with the posted primary outcome values. The registry record does not explain the relationship between the enrollment figure and the outcome denominators, so no explanation should be inferred.

The listed sponsor was The University of Texas Health Science Center, Houston. The recorded study start was 2020-07-01, primary completion was 2022-03-30, and status is completed. Masking is recorded as single, but which parties were masked is not reported in the registry record. Details of the randomization procedure, allocation concealment, protocol deviations and treatment adherence are also not reported in the registry record.

The primary outcome was average daily opioid use measured in MME per day during in-hospital days, up to 6 weeks post hospital admission. The summary identifies the intervention as a ketamine drip together with usual care and the comparator as usual care. Secondary outcomes include pain measured by the Numeric Rating Scale and several in-hospital events and treatment measures. The registry lists 34 outcome measures, with 33 secondary outcomes posted. No comparative analysis for the primary outcome is reported in the registry record. The registry record also does not report a statistical analysis plan, the sample-size justification used in the trial design, or details of the analysis population.

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: 305 were enrolled, but 5 did not consent to continue participation in the study.

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 Average Daily Opioid Use as Measured by the Morphine Milligram Equivalents (MME) Per Day, measured over In-hospital days (up to 6 weeks post hospital admission).

The primary endpoint is average daily opioid use, expressed as morphine milligram equivalents per day. MME places opioid amounts on a common morphine-equivalent scale, which makes it possible to summarize opioid use when the particular opioids administered may differ. This is a general measurement rationale; the registry record does not report the specific conversion methods used for this study.

The stated timeframe is in-hospital days, up to 6 weeks after hospital admission. The endpoint therefore summarizes opioid use during hospitalization, rather than measuring pain intensity directly. Pain was listed separately as a secondary outcome using the Numeric Rating Scale. Opioid use and pain are related clinical measures but are not interchangeable: opioid consumption alone does not establish how much pain a participant experienced or how pain changed over time.

The registry reports a mean and a 95% confidence interval for each arm. The ketamine-plus-usual-care arm has a posted mean of 32.0 MME per day, with a 95% confidence interval of 29.0 to 36.0. The usual-care arm has a posted mean of 39.0 MME per day, with a 95% confidence interval of 35.0 to 44.0. These are arm-level summaries. The registry record does not report the precise calculation of daily use across hospital days, how missing daily measurements were handled, or a between-group estimate for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and posted summaries allow several statistical concepts to be interpreted, while important parts of the trial analysis remain undocumented in the registry record. The explanations below distinguish general statistical principles from what is recorded for this study.

What does randomization contribute?

In general, random assignment is intended to make groups comparable, on average, with respect to measured and unmeasured characteristics at the time of assignment. That supports a fair comparison when outcomes are analyzed as planned and follow-up and measurement are handled appropriately. Randomization does not guarantee that the groups will be identical, especially in a finite study, and it cannot by itself prevent bias from missing outcomes, deviations from assigned treatment or selective reporting. The registry records randomized allocation and a parallel model, but the randomization procedure and allocation concealment are not reported in the registry record.

The parallel design means the listed groups are compared as separate arms rather than as a crossover in which participants receive both interventions in sequence. The registry records single masking, but does not identify who was masked or how masking was maintained. These details matter because knowledge of treatment assignment can influence care, outcome reporting or assessment, depending on the role of the person who knows the assignment.

What does a mean and its confidence interval say?

In general, a mean is the arithmetic average of observations on a measured scale. It gives a useful summary when the average is the quantity of interest, but it can be affected by extreme values and can conceal variation or patterns across time. The primary measure is a mean of opioid use expressed in MME per day. The posted 95% confidence intervals are attached to the arm-specific means, not to a difference between arms. A confidence interval is a range produced by a statistical procedure intended to reflect uncertainty in an estimate under its assumptions; it is not a guarantee that the true value lies in the interval.

To evaluate a comparative question directly, an analysis would ordinarily report a contrast between groups, with uncertainty for that contrast and a method suited to the outcome and design. The primary endpoint's comparative estimate, confidence interval and p value are not reported in the registry record. It is therefore not possible to infer a formal primary comparison from the two means or by comparing their separate intervals. The model, covariate adjustment, handling of repeated daily measurements and assumptions about the outcome distribution are not reported in the registry record.

How should the binary secondary comparisons be read?

For a binary outcome, a risk difference describes the difference between the proportions experiencing the event in the two groups. The secondary comparisons use the ketamine-plus-usual-care arm as the reference and compare usual care against it. A negative risk difference means the posted event proportion is lower in the usual-care arm; a positive risk difference means it is higher. The sign indicates direction under that comparison convention, not whether a difference is important or reliable.

The confidence intervals and p values for those comparisons are unadjusted re-calculations from the posted summary counts. They are not reported analyses in the registry record. A confidence interval spanning zero indicates that the data are compatible with a range of differences on both sides of no difference under the calculation's assumptions. A p value measures how unusual the observed data, or more extreme data, would be under a specified null model; it is not the probability that the null hypothesis is true and does not measure the clinical importance of an effect. The registry record does not report a prespecified analysis plan for these comparisons.

Rare event counts require particular caution. When few participants experience an event, estimates can be imprecise and sensitive to a small number of observations. The wide intervals for some comparisons reflect substantial uncertainty in the range of effects compatible with the posted counts. In general, a larger study may estimate uncommon outcomes more precisely, but a planning calculation based on observed data is not proof that a particular sample size will produce a reliable finding.

What are the planning illustrations?

The planning illustrations use the observed effect as a starting point and consider detecting the full observed effect or a fraction of it. They use a two-sided significance level of 0.05, equal allocation between arms and a normal approximation. The participant counts are per arm, and they are hypothetical planning quantities rather than observed trial results. For example, the delirium illustration gives 424 participants per arm for 80% power when planning for 100% of the observed effect, and 809 participants per arm when planning for 75% of that effect. These values are illustrations based on the observed estimate; they are not the trial's original design calculation, and they are not observed power.

In general, planning for a smaller effect requires a larger sample to achieve the same target power, when other assumptions remain fixed. These calculations also depend on the validity of the observed effect as a planning input and on the assumptions used for the approximation. An observed effect may be unstable, particularly for uncommon events, so the illustrations should not be treated as a definitive design recommendation. The registry record does not report the sample-size justification used when the trial was planned.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 34 outcome measures, including 33 secondary outcomes. Examining multiple outcomes creates a multiplicity concern: in general, the chance of at least one apparently unusual result can rise as more statistical comparisons are made. Researchers may address this by prespecifying a primary outcome, using a testing hierarchy, adjusting significance thresholds, or treating secondary results as exploratory. The registry record does not report whether any multiplicity strategy was planned or used. It also does not report a hierarchy among the secondary outcomes beyond identifying the primary endpoint.

The registry record does not report a comparative analysis for the primary endpoint, and it lists no reported analyses. The unadjusted secondary comparisons described in the statistical interpretation are re-calculations from the posted counts, not analyses reported by the registry. They should not be treated as if they had been prespecified or adjusted for the full set of outcomes. The record does not report whether additional analyses were conducted outside the registry entry.

Missing-data handling is also not reported in the registry record. The entry does not specify whether all randomized participants were included in each analysis, how incomplete hospital records or missing daily opioid measurements were treated, whether participants were analyzed according to assigned group, or whether any imputation or sensitivity analyses were performed. The analysis population and the handling of protocol deviations are not reported in the registry record. These omissions limit assessment of potential bias and the reproducibility of the reported summaries.

In general, missingness can affect an estimate when the likelihood of an unobserved outcome is related to participants' characteristics or outcomes. The direction and size of any such effect cannot be determined without further information. The posted arm denominators indicate the participants associated with the outcome summaries, but do not by themselves explain missingness, exclusions or the analysis population. Accordingly, uncertainty about multiplicity and missing data should accompany interpretation of the registry results.

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.

The registry's adverse-event figures list zero participants with serious adverse events and zero with other adverse events in each arm. The recorded at-risk counts are 144 in the ketamine-plus-usual-care arm and 156 in the usual-care arm. The death counts are 1 and 6, respectively. These are registry counts; the record does not provide a causal assessment of deaths or explain their timing, causes or relationship to treatment.

Counts should be read as reported rather than as proof that no adverse events occurred beyond the registry's definitions or reporting process. Definitions, event-collection methods, observation duration for safety reporting and the criteria for judging seriousness are not reported in the registry record. The posted figures also do not establish comparative safety: a formal comparison, uncertainty interval and adjustment strategy for safety outcomes are not reported in the registry record.

In general, a zero count in a study does not show that an event is impossible or that its risk is absent. It means no event was recorded in that category for the listed group under the study's reporting process. The death counts should be kept distinct from the serious and other adverse-event counts; the registry does not state whether deaths were classified in either adverse-event category. These figures describe reported events, not the reason for the events or the overall balance of benefits and harms.

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

The primary registry results show arm-level average daily opioid use during hospitalization. The posted mean is 32.0 MME per day for ketamine plus usual care and 39.0 MME per day for usual care, with arm-specific 95% confidence intervals of 29.0 to 36.0 and 35.0 to 44.0, respectively. This is a descriptive contrast in posted means. A comparative estimate and its uncertainty are not reported in the registry record, so the record does not establish the precision of a between-group effect.

The results do not, by themselves, establish whether the groups differed in pain experience. Opioid use is a measure of medication consumption, while pain was listed separately as a Numeric Rating Scale outcome. Nor do the posted primary summaries show how opioid use evolved day by day, how much participants varied, or whether the amount of use corresponded to relief or other clinical outcomes. Those interpretations require information not reported in the registry record.

The secondary event comparisons are unadjusted and imprecise. Their confidence intervals include zero, and no multiplicity strategy is reported. They do not establish equivalence, demonstrate the absence of an effect, or settle the primary opioid-use question. The safety counts are also descriptive; no causal analysis is reported for deaths or adverse events.

In general, a completed randomized trial can inform a comparative question when its outcomes, analysis and uncertainty are reported clearly. Here, the registry entry gives useful design details and arm-level primary summaries, but it does not report the primary comparative analysis, key analysis methods, missing-data procedures or the handling of multiple outcomes. The responsible interpretation is therefore limited to what is directly posted: two arm means, selected secondary event counts and safety counts. These data do not warrant a claim that the intervention does or does not work.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why arm-level summaries and a comparative analysis answer different questions. The primary endpoint is reported as a mean with a confidence interval for each arm, but the registry record does not report an estimate or interval for the contrast between arms. A reader can describe the posted means, yet cannot assess the precision of the primary between-group effect from those summaries alone. Clear reporting of the contrast would connect the randomized design to the clinical question.

The trial also illustrates the distinction between a primary outcome and a broad set of secondary measures. Opioid use, pain ratings, uncommon in-hospital events and treatment-delivery measures represent different outcomes. A collection of secondary results cannot replace a direct analysis of the primary endpoint, and unadjusted testing across many outcomes raises the possibility of chance findings. The missing report of a multiplicity plan makes it particularly important to treat secondary comparisons cautiously.

Finally, planning illustrations based on observed effects are not the same as an original sample-size justification or observed power. Their assumptions and hypothetical nature matter, especially for rare events where estimates can be unstable. The registry entry does not report the trial's design-stage sample-size rationale or enough analysis detail to evaluate missing data, model assumptions or the population analyzed. These reporting gaps limit reproducibility and the strength of conclusions that can be drawn from the posted results, even while the randomized design and clearly stated endpoint provide a useful framework for asking the comparative question.

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 the registry record constrain interpretation. The primary endpoint is presented with arm-specific means and confidence intervals, but no between-group estimate or comparative analysis is reported. The primary outcome description does not specify how repeated daily opioid measurements were summarized at the participant level or how hospital stays of different durations contributed to the mean. The registry record also does not report the handling of missing daily values or the model used for any longitudinal assessment.

The intervention is described as ketamine plus usual care, with the study summary referring to a ketamine drip, but the registry record does not provide the dose, administration protocol, start criteria or treatment duration. The components of usual care are likewise not specified. Consequently, the intervention contrast cannot be fully characterized from the registry description alone. Eligibility criteria and participant characteristics are not reported in the registry record in the registry record, limiting assessment of how broadly the findings may apply.

For secondary outcomes, only selected event comparisons have posted counts in the available record, and the unadjusted calculations do not account for the wider set of outcomes. A multiplicity plan, missing-data strategy, analysis population and detailed statistical methods are not reported in the registry record. The adverse-event counts lack definitions, collection details and causal assessments, while the death counts lack reported causes or timing. These are limitations of what can be concluded from the recorded information; they do not establish that additional procedures or analyses were absent outside the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ketamine for Acute Pain Management After Trauma — NCT04129086.
• Registry record last updated 2023-04-21; status last verified 2023-03.
• Results first posted 2023-04-21.
• 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

NCT04129086, titled “Ketamine for Acute Pain Management After Trauma,” is a completed randomized, single-masked, parallel-group Phase 4 trial sponsored by The University of Texas Health Science Center, Houston. The recorded enrollment is 305. The study compared ketamine plus usual care with usual care alone in trauma patients.

The primary endpoint was average daily opioid use in MME per day during in-hospital days, up to 6 weeks after hospital admission. The posted arm means were 32.0 for ketamine plus usual care and 39.0 for usual care, with their respective 95% confidence intervals. The registry record does not report a comparative analysis for this primary endpoint. It lists multiple secondary outcomes and posts counts for selected in-hospital events, alongside adverse-event and death counts. Important details—including the primary analysis method, missing-data handling, analysis population and multiplicity plan—are not reported in the registry record.