This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Pain Reduction With Intranasal Medications for Extremity Injuries (NCT02778880), a randomized phase 3 study. The primary outcome is Difference From Baseline in Visual Analog Scale Pain Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02778880 |
| Phase | Phase 3 |
| Condition | Pain, Traumatic Limb Injury |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 90 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Children's Hospital Medical Center, Cincinnati |
| Results posted | Yes |
2. Clinical Question
Population
Children presenting to an Emergency Department with acute extremity injuries and associated pain. The registry record reports 90 enrolled participants. The age range and further eligibility details are not reported in the registry record.
Intervention
A single intranasal dose of ketamine at 1.5 mg/kg, described as sub-dissociative dosing.
Comparator
A single intranasal dose of fentanyl at 2 mcg/kg.
Primary question
The trial compared the analgesic effects of the two medications. Its primary outcome was the difference from baseline in visual analog scale pain score at 30 minutes after study medication. The registry record posts mean changes and confidence intervals for each group, but no direct comparison estimate or reported analysis for the primary outcome.
3. Trial Design
The registry record describes a randomized, quadruple-masked, parallel-group phase 3 trial sponsored by Children's Hospital Medical Center, Cincinnati. The study status is completed, and enrollment is listed as 90. The study began on 2016-03-31, with primary completion on 2017-02-22. The registry record does not describe the specific allocation procedure or identify which people were included in the quadruple masking.
Participants received one intranasal dose of either ketamine, 1.5 mg/kg, or fentanyl, 2 mcg/kg. The stated study population was children presenting to the Emergency Department with acute extremity injuries. Further eligibility criteria, including age limits, are not reported in the registry record.
The primary outcome was mean difference from baseline in visual analog scale pain score at 30 minutes after study medication. The posted primary outcome population includes 43 participants in the ketamine group and 42 in the fentanyl group. Its description says that one ketamine-group participant had no baseline pain score documented and that four participants withdrew: one in the ketamine group and three in the fentanyl group. The registry record does not describe the timing or reasons for withdrawal, or the analysis population as an intention-to-treat or per-protocol population.
The record lists 23 outcome measures and 22 posted secondary outcomes. It does not report a protocol, a detailed statistical analysis plan, the planned sample-size justification, interim analyses, or a multiplicity procedure. The observed enrollment and the posted outcome populations should therefore not be treated as evidence of the trial's original design assumptions.
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
| Stage | Ketamine | Fentanyl |
|---|---|---|
| STARTED | 45 | 45 |
| COMPLETED | 44 | 42 |
| NOT COMPLETED | 1 | 3 |
Analysis population for the primary outcome, as defined in the registry: One patient in the ketamine group did not have a baseline pain score documented and four patients withdrew from the study (1 in the ketamine group, 3 in the fentanyl group), resulting in 43 patients randomized to the ketamine group and 42 patients randomized to the fentanyl group included in the primary outcome analysis.
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.
| Characteristic | Unit | Ketamine | Fentanyl | Total |
|---|---|---|---|---|
| Participants analysed | 44 | 42 | 86 | |
| Age, Continuous | years | 11.8 (SD 2.6) | 12.2 (SD 2.3) | 12.0 (SD 2.5) |
| Sex: Female, Male: Female | Participants | 18 | 11 | 29 |
| Sex: Female, Male: Male | Participants | 26 | 31 | 57 |
| Race/Ethnicity, Customized: Race/Ethnicity – White | Participants | 30 | 29 | 59 |
| Race/Ethnicity, Customized: Race/Ethnicity – Black | Participants | 11 | 10 | 21 |
| Race/Ethnicity, Customized: Race/Ethnicity – Hispanic | Participants | 0 | 2 | 2 |
| Race/Ethnicity, Customized: Race/Ethnicity – Other | Participants | 3 | 1 | 4 |
| Weight | kilograms | 45.8 (SD 14.4) | 50.8 (SD 22.8) | 48.3 (SD 18.6) |
| Mechanism of Injury: Sports Related/Recreational | Participants | 30 | 26 | 56 |
| Mechanism of Injury: Motor Vehicle Accident | Participants | 1 | 2 | 3 |
| Mechanism of Injury: Fall | Participants | 10 | 13 | 23 |
| Mechanism of Injury: Other | Participants | 3 | 1 | 4 |
| Time of injury prior to arrival | minutes | 43.0 (27.0 to 63.0) | 51.5 (30.0 to 85.0) | 47.3 (28.5 to 74.0) |
| Extremity: Upper Extremity | participants | 33 | 28 | 61 |
| Extremity: Lower Extremity | participants | 13 | 15 | 28 |
| Diagnosis: Fracture | participants | 39 | 34 | 73 |
| Diagnosis: Dislocation | participants | 4 | 2 | 6 |
| Diagnosis: Sprain/Strain | participants | 1 | 5 | 6 |
| Diagnosis: Other | participants | 2 | 1 | 3 |
| Reduction Required | Participants | 19 | 23 | 42 |
| Sedation Required | Participants | 19 | 20 | 39 |
| Analgesic Prior to Arrival: Ibuprofen | Participants | 4 | 4 | 8 |
| Analgesic Prior to Arrival: Acetaminophen | Participants | 1 | 2 | 3 |
| Analgesic Prior to Arrival: Naproxen | Participants | 0 | 1 | 1 |
| Analgesic Prior to Arrival: No Analgesic | Participants | 39 | 35 | 74 |
| Initial VAS score | score on a scale | 74.7 (SD 15.3) | 72.0 (SD 18.6) | 73.4 (SD 17.0) |
| Baseline Heart Rate | beats per minute | 90.8 (SD 15.2) | 88.6 (SD 14.8) | 89.7 (SD 15.0) |
| Baseline Respiratory Rate | breaths per minute | 22.1 (SD 6.6) | 23.0 (SD 7.4) | 22.5 (SD 7.0) |
6. Primary Endpoint
The registry lists the primary outcome as Difference From Baseline in Visual Analog Scale Pain Score, measured over 30 minutes after study medication.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean change from baseline in the visual analog scale pain score, assessed 30 minutes after study medication. The scale is described as a self-reported pain score from 0 to 100 millimeters, where 0 is no pain and 100 is the worst possible pain. A decrease in score indicates a decrease in reported pain severity.
Measuring change from baseline expresses the follow-up score in relation to the participant's initial score. This can make the outcome easier to interpret as a change during the study period rather than as a follow-up value alone. The endpoint is continuous: it can take values across a range rather than only classifying participants into categories. The registry reports the mean change and a 95% confidence interval for each treatment group.
The posted endpoint results describe each group separately. Although they show average changes from baseline, the registry record does not post a direct between-group estimate, confidence interval, or reported statistical test for the primary endpoint. Separate group estimates do not by themselves quantify the treatment contrast or establish that the groups differ.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted mean change in visual analog scale pain score was -30.6 in the ketamine group, with a 95% confidence interval from -35.8 to -25.4. In the fentanyl group, the mean change was -31.9, with a 95% confidence interval from -37.2 to -26.6. The negative values indicate decreases from baseline according to the endpoint's scoring description. The confidence intervals express uncertainty around each group's mean change; they are not ranges containing every participant's change.
These results describe average within-group changes. They do not provide the direct comparison needed to estimate the difference between the ketamine and fentanyl groups. The registry record does not post a primary-outcome comparison estimate or a reported analysis for that contrast. The means alone should not be converted into a new contrast, and the individual confidence intervals should not be treated as a substitute for a confidence interval around the between-group difference.
The recorded primary analysis population includes 43 ketamine-group participants and 42 fentanyl-group participants. The outcome description notes one missing baseline pain score in the ketamine group and four withdrawals, split between the groups. The record does not explain how missing data were handled beyond describing the participants included in the primary outcome population. It also does not identify this population using a standard analysis-population label.
The interpretation is therefore limited to the posted descriptive estimates and their precision. A confidence interval shows the range of values compatible with the data under the analysis assumptions; it does not establish clinical importance, equivalence, or non-inferiority. The registry record does not report a prespecified clinical threshold for interpreting the scale or a primary between-group test. The posted summaries alone cannot answer whether one treatment produced a larger average change than the other under the trial's analysis plan.
The secondary outcome summaries cover other measures, including heart rate, respiratory rate, and systolic blood pressure at 15 minutes. Their recalculated contrasts are exploratory and are not replacements for the missing primary comparison. Secondary outcome availability and analysis details are incomplete in the registry record, and the record does not report multiplicity adjustment. These limitations matter when reading isolated secondary p-values or confidence intervals.
9. Statistical Methods Explained
The primary endpoint is continuous, and the registry reports means with 95% confidence intervals. Statistical summaries for continuous outcomes describe a central value and the uncertainty around an estimate. A mean is an average; it does not show the full distribution of individual observations. The confidence interval describes uncertainty in the estimated mean under the assumptions of the analysis, rather than the range of individual participants' scores.
What does change from baseline represent?
The primary result is a within-group change from the baseline pain score to the score 30 minutes after study medication. A negative change represents a decrease on the scale, because the registry states that decreasing scores indicate decreasing reported pain severity. The reported means are group summaries. They do not show how many participants improved, how much individual scores varied, or how many participants had increases rather than decreases.
For a treatment comparison, the central quantity is usually a contrast between groups, such as the difference between their mean changes. A direct contrast uses the trial's chosen analysis and can account for the way the data were collected and analyzed. The registry record posts the group means and their confidence intervals but does not post a primary contrast or test. It would be inappropriate to create a new contrast by subtracting the reported means because that would be a new calculation and would not reproduce a trial analysis or its uncertainty.
How should confidence intervals be read?
General statistical explanation: a confidence interval gives a range of estimates consistent with the observed data under a statistical procedure and its assumptions. A narrower interval indicates greater precision for the estimated quantity than a wider interval, while an interval does not remove uncertainty. A 95% confidence interval is not a guarantee that the true value lies inside that particular interval, nor does it describe where 95% of individual observations fall.
Here, the posted intervals apply to the mean change within each group. They do not directly describe uncertainty in a difference between groups. Confidence intervals for separate groups cannot answer every question about a group contrast; the direct contrast and its uncertainty are the relevant evidence for that question. The registry record does not report them for the primary endpoint.
What do the secondary comparisons represent?
The secondary outcomes include continuous measures summarized as means and standard deviations. The posted summaries include heart rate, respiratory rate, and systolic blood pressure at 15 minutes after study medication. The additional mean differences, confidence intervals, and p-values are recalculated, simple unadjusted comparisons from the posted summary statistics, rather than analyses reported in the registry record. They do not incorporate an adjustment for other outcomes or a stated covariate model.
General statistical explanation: a standard deviation describes variation among individual observations, while a standard error describes uncertainty in an estimated mean. A confidence interval around a mean difference reflects uncertainty in the contrast, given the calculation's assumptions. A p-value measures how unusual data at least as incompatible with a null hypothesis would be under that hypothesis and the specified model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance.
Secondary comparisons based on summary statistics are especially limited when the analysis methods used by the trial are not reported. They may not match a prespecified model, account for repeated measurements, or handle missing observations as the trial investigators did. The registry lists no reported analyses for these secondary results. The recalculated estimates should therefore be read as simple descriptive contrasts, not as sponsor-reported inferential conclusions.
What are the sample-size illustrations?
General statistical explanation: a sample-size calculation estimates how many participants would be needed under specified assumptions to detect an effect with a chosen power and significance level. Such planning figures depend on the assumed effect, variability, allocation, and statistical method. They are not evidence that a trial had that power after the fact.
The registry record explicitly labels its planning figures as illustrations based on observed effects, not as the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These illustrations should not be called observed power or used to infer the original sample-size rationale. The original sample-size justification is not reported in the registry record.
General statistical explanation: when several outcomes or comparisons are tested, the chance of finding at least one apparently unusual result can increase if each test is interpreted in isolation. A multiplicity procedure can address this issue, but the appropriate approach depends on the study questions and analysis plan. The registry record does not report such a procedure. This makes unadjusted secondary p-values less definitive, particularly when there are multiple outcome measures.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 23 outcome measures and 22 posted secondary outcomes. It does not report a multiplicity procedure, a hierarchy for primary and secondary hypotheses, or a statistical analysis plan describing which comparisons were confirmatory. The record lists zero reported analyses. This absence does not establish what analyses were conducted outside the registry; it means the registry record does not report them.
General statistical explanation: multiplicity arises when several outcomes, time points, or comparisons are assessed. If each test is judged separately without adjustment, the overall chance of at least one false-positive result can rise. Adjustment methods and prespecified hierarchies can help control that risk, but their interpretation depends on the planned questions. Since no approach is reported, the recalculated secondary p-values should not be read as multiplicity-adjusted evidence.
The primary outcome population description notes one ketamine-group participant without a documented baseline pain score and four withdrawals, one from ketamine and three from fentanyl. It reports 43 ketamine-group and 42 fentanyl-group participants in the primary outcome population. The record does not describe imputation, other missing-data handling, reasons for withdrawal, or sensitivity analyses. It also does not say whether the primary analysis followed an intention-to-treat, modified intention-to-treat, or per-protocol definition.
Other posted summaries use different group counts from the primary outcome population. The safety counts list 44 participants at risk in the ketamine group and 42 in the fentanyl group, and the posted 15-minute heart-rate summary also uses 44 and 42. These outcome-specific denominators should be read as reported for each measure rather than assumed to represent one universal analysis population. The registry record does not explain the differences in denominators or provide a complete account of data availability by outcome.
Interim analyses, stopping rules, and the handling of protocol deviations are not reported in the registry record. The original sample-size justification is also not reported. These omissions limit assessment of whether the posted analyses follow a prespecified plan and how missing observations or multiple testing were addressed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Ketamine | 0 | 44 | 0.0% |
| Fentanyl | 0 | 42 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ketamine | 0 of 44 |
| Fentanyl | 0 of 42 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ketamine | 34 of 44 |
| Fentanyl | 13 of 42 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ketamine | Fentanyl |
|---|---|---|---|
| Drowsiness | Nervous system disorders | 21 of 44 | 10 of 42 |
| Dizziness | Nervous system disorders | 9 of 44 | 7 of 42 |
| Unpleasant Taste | Gastrointestinal disorders | 9 of 44 | 2 of 42 |
| Nausea/Vomiting | Gastrointestinal disorders | 3 of 44 | 0 of 42 |
| Vision Changes | Eye disorders | 2 of 44 | 0 of 42 |
| Lightheadedness | Nervous system disorders | 2 of 44 | 0 of 42 |
| Dysphoria/Dissociation | Nervous system disorders | 1 of 44 | 0 of 42 |
| Pruritis | Skin and subcutaneous tissue disorders | 1 of 44 | 0 of 42 |
| Headache | Nervous system disorders | 0 of 44 | 1 of 42 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 44 | 1 of 42 |
The registry safety summary reports zero serious adverse events among 44 participants at risk in the ketamine group and zero among 42 at risk in the fentanyl group. It also reports zero deaths in both groups. The record lists no top serious adverse event terms. These are counts recorded in the registry and describe the reported serious-event experience in the stated groups.
The summary also reports other, non-serious adverse events affecting 34 of 44 ketamine-group participants and 13 of 42 fentanyl-group participants. These counts should not be conflated with serious adverse events. The registry record does not provide event terms or definitions in the listed summary, nor does it report a comparative statistical analysis of these safety counts.
General statistical explanation: observing zero serious events in a group does not prove that the underlying risk is zero. Safety counts are influenced by the number of participants observed, the length and completeness of follow-up, and how events are defined and collected. The registry record does not report the adverse-event observation window or detailed ascertainment procedures. The counts therefore describe the posted record, but do not by themselves establish comparative safety or rule out uncommon events.
12. What the Result Does, and Does Not, Mean
The primary results show that both groups had negative mean changes in visual analog scale pain score from baseline at 30 minutes after study medication. The registry describes a decrease in this score as a decrease in reported pain severity. The 95% confidence intervals quantify uncertainty around each group's mean change, but they do not show the distribution of individual responses or identify the number of participants who experienced any particular amount of change.
The posted results do not establish a direct difference between the treatments on the primary endpoint. No primary between-group estimate, confidence interval, or reported test is included in the registry record. In particular, the separate group summaries do not establish equivalence or non-inferiority, and their interpretation cannot substitute for a direct comparison under a prespecified analysis.
The secondary measures provide additional recorded information, but their analyses are not reported in the registry. The available secondary contrasts are recalculated from group summary statistics and are unadjusted. They should not be used to make a definitive claim about the treatments, especially without a reported multiplicity approach and full analysis plan. The safety figures similarly describe recorded event counts rather than proving that serious events cannot occur or providing a complete comparative safety assessment.
General statistical explanation: statistical significance, clinical importance, and precision are distinct ideas. A p-value addresses compatibility with a statistical null model, not the size or practical meaning of an effect. A confidence interval helps communicate precision, but interpretation also depends on the outcome scale, study design, missing data, and analysis choices. The registry record does not report a clinical threshold for interpreting a meaningful change on the pain scale.
The evidence represented by the registry is consequently descriptive for the primary outcome and limited for treatment comparison. It documents the trial design, group-specific mean changes, selected secondary summaries, and safety counts. It does not provide enough information to infer a complete statistical analysis or to make a definitive comparative conclusion from the registry record alone.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction in clinical-trial reporting: group-specific outcome summaries and a treatment contrast answer different questions. The primary results report average change within each treatment group, while the central comparative question concerns how those changes differ between groups. Without a posted contrast and its uncertainty, the registry record does not quantify the primary treatment comparison.
The record also shows why analysis populations and denominators matter. The primary pain outcome uses 43 participants in the ketamine group and 42 in the fentanyl group, while some secondary and safety summaries list different counts. Different outcome-specific denominators can arise for different reasons, but those reasons are not explained in the registry record. Transparent reporting of who contributed data to each analysis is essential for understanding the estimates.
Multiplicity is another central statistical issue. A trial can measure many outcomes, but interpreting each unadjusted result as a separate confirmatory finding can overstate the evidence. Here, the registry lists numerous outcomes and does not report a multiplicity procedure or analysis hierarchy. That context makes it particularly important to distinguish the primary endpoint from exploratory secondary summaries.
Finally, planning illustrations based on observed effects do not reveal the original design rationale or establish observed power. The registry itself characterizes those figures as planning illustrations, while the trial's own sample-size assumptions are not reported. The trial therefore demonstrates how registry summaries can be useful while still leaving important questions about prespecification, missing data, analysis choices, and comparative inference unanswered.
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 key limitation for interpreting the primary outcome is that the registry posts group-specific mean changes and confidence intervals but not a direct between-group estimate or reported analysis. The primary endpoint is therefore described, but the main comparative question is not quantified in the registry record. The record also does not report a clinically meaningful threshold for interpreting the scale.
The primary outcome population description identifies one missing baseline pain score and four withdrawals, but does not explain the reasons for withdrawal, timing of missingness, or missing-data method. The analysis population is not identified as intention-to-treat or by another standard label. Some secondary and safety summaries use different denominators, and the registry record does not explain the differences.
Reporting of secondary outcomes is incomplete for interpretation: the record lists multiple outcomes, but not all have results in the posted summaries, and no analysis details are reported. The recalculated secondary comparisons are simple unadjusted comparisons based on summary statistics. No multiplicity adjustment, analysis hierarchy, or secondary-outcome statistical plan is reported, so isolated secondary findings require caution.
The record does not report the original sample-size justification, allocation-concealment details, masking roles, interim analyses, stopping rules, protocol deviations, or a full statistical analysis plan. It also does not report detailed adverse-event terms or the safety follow-up window. These are limitations of what can be assessed from the registry record; they do not establish that such procedures or information were absent from trial conduct or other documentation.
The study enrolled 90 participants, but the posted primary outcome population is smaller. The registry record does not provide enough information to determine how representative the analyzed participants are of everyone enrolled or how any exclusions may have affected the estimates. General statistical explanation: missingness and analysis choices can affect both the estimate and its uncertainty, so transparent accounting is important for evaluating robustness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pain Reduction With Intranasal Medications for Extremity Injuries — NCT02778880.
- Registry record last updated 2020-09-01; status last verified 2018-10.
- Results first posted 2020-09-01.
- 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.
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18. Record Summary
NCT02778880 is a completed randomized, quadruple-masked, parallel-group phase 3 trial of intranasal ketamine versus intranasal fentanyl for pain associated with acute extremity injuries in children. Enrollment was 90. Participants received a single intranasal dose of ketamine 1.5 mg/kg or fentanyl 2 mcg/kg.
The primary outcome was mean change from baseline in visual analog scale pain score at 30 minutes. The registry reports a mean change of -30.6 for ketamine and -31.9 for fentanyl, with a 95% confidence interval for each group. It does not report a direct between-group primary analysis.
Secondary outcomes include pain, sedation, rescue analgesia, and physiologic measures. Some secondary comparisons are recalculated from posted summaries and are unadjusted; the registry does not report multiplicity handling or a complete statistical analysis plan. Serious adverse events and deaths are reported as zero in both groups, with other adverse events recorded in each group. The original sample-size justification, detailed missing-data methods, and full analysis populations are not reported in the registry record.