Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department (NCT02489630), a randomized phase 4 study. The primary outcome is Change in Level of Pain Control as Reported on the NRS-11.

2. Clinical Question

The study therefore addresses whether adding ketamine to opiate medication is associated with a different course of reported pain scores than adding saline, while both groups receive an opiate analgesic. The record describes the intended comparison, not evidence that one approach produced better pain control or required less opiate medication. It also raises patient satisfaction as a question in its brief summary, but satisfaction is not identified among the listed outcome measures.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group Phase 4 study. The registry lists an enrollment of 116 and a completed status. Carilion Clinic is identified as the sponsor. The recorded study start was 2013-09, and primary completion was 2015-03.

Participants were allocated to receive either 0.1 mg/kg ketamine with an opiate analgesic or 0.1 mL/kg normal saline with an opiate analgesic. The parallel-group design means the planned treatment comparison is between groups receiving different adjuncts. The registry labels the allocation randomized and masking quadruple, but it does not identify which specific roles were masked, describe the randomization procedure, or report whether masking was assessed.

The primary outcome is a continuous patient-reported pain measure, with the mean and standard deviation specified as the summary statistics. Pain was assessed at enrollment, at medication administration, and at post-medication timepoints of 30, 60, 90, and 120 minutes. The registry describes the enrollment assessment as occurring up to 20 min before T=0. T=0 was the time of medication administration; the record notes that administration could be delayed by up to 20 minutes for study-drug retrieval and related checks.

The registry lists three outcome measures and a secondary outcome concerning opiate dosage in morphine equivalents. It does not report the statistical analysis plan, the rationale for the enrollment target, or whether interim analyses were planned. No numerical results for the primary or secondary outcomes are reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Total number of study subjects; received intervention or placebo.

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 in Level of Pain Control as Reported on the NRS-11, measured over 20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration.

The primary endpoint is change in patient-reported pain control on the NRS-11. The scale is described as running from 0, meaning no pain at all, to 10, meaning the most severe pain. The registry specifies mean and standard deviation as the summary statistics and describes assessments from the pre-medication period through 120 minutes after medication administration.

A repeated pain measure can describe both the level of reported pain and how that level changes over time. The assessment around enrollment provides a pre-medication reference, while the T=0 assessment is tied to the time of medication administration. Later assessments describe pain after treatment. These times are not interchangeable: the enrollment assessment could occur up to 20 min before T=0, and T=0 marks medication administration rather than enrollment.

In general, repeated measurements can help characterize the course of an outcome rather than relying on a single observation. Comparing groups across those measurements requires an analysis that accounts for their timing and for the fact that measurements from the same participant are related. The registry record does not report the numerical pain scores, the estimated change within either group, or a between-group comparison. It therefore does not establish the size or precision of any difference in pain scores.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as continuous and specifies the mean and standard deviation. These summaries describe the average pain score and the spread of individual scores around that average. A mean alone does not show how variable the responses were; a standard deviation gives information about that variability, though it does not describe every feature of the score distribution.

What does a confidence interval convey?

In general, a confidence interval expresses the statistical uncertainty around an estimated effect under the assumptions of the analysis. A narrow interval indicates more precise estimation than a wide interval, while both its location and width matter. An interval for a treatment-group contrast can help readers judge which effect sizes remain compatible with the data and model. The registry record does not report a confidence interval for the primary outcome, so its precision cannot be assessed from the posted results.

How should repeated pain measurements be analyzed?

The pain assessments are repeated observations over time. In general, measurements from the same participant tend to be related, so an analysis should account for that dependence rather than treating every measurement as if it came from an unrelated person. A longitudinal model can estimate group patterns over time and, depending on its specification, test whether those patterns differ. Another approach may focus on selected timepoints or changes from baseline. Each approach targets a different statistical question. The registry does not report which method was used, the model structure, or the primary contrast used in the sponsor's analysis.

The timing definitions matter when interpreting change. The initial assessment was taken at enrollment or randomization, up to 20 min before T=0. T=0 was the time of medication administration, and the record allows for up to a 20-minute delay before receiving study drug. An analysis treating the initial and T=0 assessments as equivalent would obscure that distinction. The registry does not specify how the timing difference was handled analytically.

Why can over-dispersion matter?

In general, over-dispersion means that observed variation is greater than a model's assumptions allow. If a model underestimates variability, standard errors may be too small and confidence intervals too narrow, making statistical evidence appear more precise than it is. This is a general concern for statistical modeling, not a reported feature of this trial. The registry identifies a continuous outcome summarized by means and standard deviations, but it does not report a fitted model or evidence about over-dispersion.

What does a p-value answer?

In general, a p-value describes how compatible the observed data are with a specified null hypothesis under the chosen statistical model. It does not measure the probability that the null hypothesis is true, the size of an effect, or its clinical importance. A p-value is most informative alongside an effect estimate and its confidence interval. No p-value for the primary pain outcome is reported in the registry record, so statistical significance cannot be judged from the record.

What are sample-size illustrations?

The registry's planning assumptions describe illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. In general, a sample-size calculation asks how many participants per arm would be needed under specified assumptions to detect a chosen effect with a chosen power. The answer depends on the assumed effect and variability, among other design choices. These calculations are planning illustrations, not observed power: they do not tell how likely this completed study was to detect an effect after the fact. The registry does not report the original sample-size justification, and the illustrations should not be mistaken for that justification.

For any such calculation, the choice of effect matters. A calculation based on the full observed effect is not equivalent to planning for a smaller effect. The assumptions also require a clear outcome and contrast; multiple assessment times can yield different candidate effects. The registry record does not identify the original target effect or describe how its sample-size target was chosen. No numerical planning results are reported in the registry record, so no specific required sample size can be interpreted from these assumptions alone.

Randomization supports a planned comparison of the assigned groups, while masking can reduce some forms of influence on treatment delivery or outcome assessment. Neither feature by itself supplies the missing outcome estimates, guarantees that groups remained comparable in all respects, or establishes that the analysis followed a particular method. The registry reports randomized allocation and quadruple masking but does not provide procedural detail sufficient to evaluate these features further.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is measured at multiple times: an initial assessment, T=0, and post-medication assessments at 30, 60, 90, and 120 minutes. Testing separate group differences at multiple times can raise a multiplicity question because the more comparisons considered, the greater the chance of at least one apparently unusual result under a set of null hypotheses. In general, an analysis can address this by defining a primary contrast in advance or using an appropriate adjustment or joint model. The registry record does not report a multiplicity strategy or identify a single timepoint as the primary comparison.

The registry lists a secondary outcome for opiate dosage in morphine equivalents. It also mentions patient satisfaction in the brief summary, but satisfaction is not among the listed outcome measures. How the secondary outcome was analyzed, whether additional outcomes were examined, and whether any multiplicity adjustment was used are not reported in the registry record. The record lists no statistical analyses, so it is not possible to determine which comparisons were performed or how they were interpreted.

Missing-data handling and analysis populations are also not reported in the registry record. The outcome description refers to study subjects who received intervention or placebo, but it does not specify how participants with missing pain assessments were handled, whether all randomized participants were included in the analysis, or whether any per-protocol or other population was used. The record does not give the number of missing measurements at each assessment or reasons for missingness. Those details are important because incomplete follow-up can affect both the precision and potential bias of a repeated-measures comparison. No assumptions or sensitivity analyses for missing data are described.

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 0% reporting threshold.

The registry's adverse-event entries report zero serious adverse events among 53 participants at risk in the ketamine group and zero among 63 participants at risk in the placebo group. It also reports zero other adverse events among 53 participants at risk in the ketamine group and zero among 63 participants at risk in the placebo group. No serious-event terms are listed.

These entries describe what was recorded in the registry's adverse-event results. They do not provide event definitions, observation duration, methods of collection, or detail about the completeness of reporting. The death fields are null; deaths are therefore not reported in the registry record, rather than documented as zero. The zero event counts should not be interpreted as proof of no risk or as a comparison establishing equivalent safety. The record does not provide statistical estimates for between-group safety differences.

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

The registry record establishes that the study was designed to compare low-dose ketamine plus an opiate analgesic with normal saline plus an opiate analgesic for acute pain in the emergency department. It identifies patient-reported NRS-11 pain scores as the primary outcome and describes repeated assessments from before medication through 120 minutes after administration. It also lists a secondary opiate-dosage outcome.

What the record does not establish is the direction or size of any between-group difference in pain scores, how precisely such a difference was estimated, or whether any statistical test crossed a threshold for significance. Numerical primary and secondary outcome results are not reported in the registry record. Accordingly, the record cannot establish that adding ketamine improved pain control, had no effect, changed opiate requirements, or produced equivalent outcomes. It also cannot establish a satisfaction result.

In general, a statistical result should be read in terms of its estimate, uncertainty, analysis population, and outcome definition. A p-value alone would not establish clinical importance, and a non-significant result would not by itself prove that groups were equivalent. Equivalence or non-inferiority requires a prespecified framework and analysis; neither is reported in the registry record. This study's stated comparison and completed status do not substitute for those results.

The adverse-event entries report zero serious and zero other adverse events in each group's listed at-risk population, but the record lacks the further details needed to interpret how completely events were captured. Those entries are not evidence of absence of all possible harms. The null death fields also mean mortality information is not reported in the registry record. Overall, the posted information describes the trial question, design, outcome timing, and selected safety counts, but does not provide the efficacy analysis needed to answer the primary question.

13. Why This Trial Matters Statistically

This trial is statistically notable for defining an outcome that is measured repeatedly rather than at a single follow-up point. Pain is assessed at enrollment, at medication administration, and at several post-medication times. That structure makes the distinction between a single-timepoint comparison and a comparison of the pain trajectory important. It also makes the treatment contrast dependent on how the timing and within-participant correlation are handled.

The registry's timing details reinforce a practical point for analysis: an enrollment assessment could occur up to 20 min before T=0, while T=0 is anchored to medication administration and could itself follow a delay of up to 20 minutes. The initial measure and the medication-time measure therefore have different definitions. Clear outcome definitions are essential to interpreting a change score or longitudinal model.

The design also illustrates why a registry question is not the same as a reported statistical result. Randomization and masking describe important features of the study design, but a reader still needs effect estimates, uncertainty, and analysis details to assess what the data show. Here, the registry describes the primary measure and several outcomes, yet lists no analyses and no numerical primary-outcome findings.

Finally, planning calculations and observed results have different roles. A sample-size illustration based on an observed effect is not observed power and cannot recover the missing analysis. This distinction matters when readers assess what a completed trial can establish: the design indicates what comparison was intended, while the estimates and their precision are needed to interpret the evidence.

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.

Important limitations of interpretation arise from the limited outcome reporting in the registry record. It gives no numerical pain scores, group contrasts, confidence intervals, or p-values. The direction and magnitude of the primary result therefore cannot be assessed. Although an opiate-dosage outcome is listed, its results are not reported. The brief summary raises patient satisfaction as a question, but the listed outcome measures do not include satisfaction results.

The primary outcome has several assessment times, but the record does not identify a single primary timepoint or report how repeated measurements were modeled. It also does not report a multiplicity plan. Without these details, readers cannot determine how the intended primary comparison was defined or how results across times would be interpreted together.

Further details about the population and conduct are not reported in the registry record, including eligibility criteria, participant characteristics, the randomization procedure, and the specific roles covered by quadruple masking. The record also does not report missing outcome counts, reasons for missingness, the analysis population, or methods for handling incomplete measurements. These omissions limit assessment of the population represented and the robustness of any analysis.

The adverse-event entries do not include event definitions, collection methods, or observation duration, and the death fields are null. The registry does not report the original sample-size justification or statistical analysis plan. These limitations do not determine what the trial's unreported results would show; they specify why the registry information alone is insufficient for a full assessment of the study's findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department — NCT02489630.
• Registry record last updated 2021-03-12; status last verified 2021-02.
• Results first posted 2021-03-12.
• 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.

18. Record Summary

The registry describes a completed, randomized, quadruple-masked, parallel-group Phase 4 study sponsored by Carilion Clinic. The recorded start was 2013-09, primary completion was 2015-03, and enrollment was 116.

The comparison was 0.1 mg/kg ketamine plus an opiate analgesic versus 0.1 mL/kg normal saline plus an opiate analgesic. The primary outcome was change in patient-reported NRS-11 pain scores, assessed at enrollment, at medication administration, and at post-medication times through 120 minutes. A secondary outcome concerned opiate dosage in morphine equivalents.

The registry record does not report numerical primary- or secondary-outcome results or statistical analyses. It reports zero serious and zero other adverse events in the listed at-risk participants in each group; mortality information is not reported in the registry record.