Ketamine and Propofol for Upper Endoscopy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine and Propofol for Upper Endoscopy (NCT02295553), a randomized phase 4 study. The primary outcome is Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's Esophagus.

2. Clinical Question

3. Trial Design

The registry describes a Phase 4, randomized, double-masked, parallel-group study, with enrollment of 56 and completed status. The study was sponsored by The Hospital for Sick Children. The recorded start was 2013-07 and primary completion was 2016-12. These details describe the registered design and timeline; they do not supply additional information about how randomization or masking was implemented.

Four ketamine dose groups are listed: 0 mg/kg, 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg. Each group also received propofol. The arm descriptions specify a starting propofol dose for the first patient in each group and prescribe subsequent increases or decreases according to the Dixon Up and Down method. The starting propofol doses and adjustment increments differ by ketamine group. The registry does not describe further operational details of that dose-adjustment process.

The primary outcome is the propofol dose required to prevent movement on insertion of the endoscope into the esophagus. The posted arm summaries list 14 participants in the 0 mg/kg group, 14 in the 0.25 mg/kg group, 13 in the 0.5 mg/kg group, and 14 in the 1.0 mg/kg group. The record also identifies secondary outcomes concerning apnea duration, respiratory events during the procedure, and side effects and complications during recovery. Numerical results are posted for apnea duration, but not for the other named secondary outcomes.

The registry does not report details of the randomization sequence, allocation concealment, masking procedures, participant flow, or the rationale for the enrollment target. Those features should not be inferred from the labels randomized and double-masked alone.

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

Analysis population for the primary outcome, as defined in the registry: Dose of propofol required to prevent movement upon insertion of endoscope

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 Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's Esophagus, measured over This outcome is measured at the time of insertion of the endoscope into the esophagus..

The primary endpoint is the dose of propofol required to prevent movement in response to insertion of the endoscope into the esophagus. It is reported as a mean in mg/kg with a 95% confidence interval for each ketamine group. The registry frames the endpoint around the propofol ED50: the dose associated with an adequate depth of anesthesia to prevent minimal or no movement in 50% of subjects. This makes the endpoint a dose-finding measure, rather than a direct comparison of a clinical event rate.

Movement at insertion is used as an observable response to the procedure and the administered medication combination. Estimating the propofol dose associated with that response can characterize how the recorded dose requirement varies with ketamine dose. That interpretation remains specific to the registered population, outcome definition, and study setting. The registry does not give further detail about how movement was assessed, who assessed it, or how borderline responses were classified.

The posted values are group means with confidence intervals, not individual participant doses or a reported ED50 model estimate. No inferential comparison of the primary endpoint is posted. The means can therefore describe the pattern across groups, while the confidence intervals convey uncertainty around each group estimate; they do not by themselves provide a formal test of differences between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it is a dose measured in mg/kg and summarized by a mean. A mean describes the central value of the observations in a group. In this dose-finding setting, the outcome is intended to reflect how much propofol was required to prevent movement during endoscope insertion. The endpoint is not a count of participants with an event, and the reported group means should not be read as probabilities.

What does the confidence interval communicate?

A confidence interval expresses uncertainty about an estimate under the statistical method used to construct it. The registry reports 95% confidence intervals around each primary group mean. A narrower interval indicates greater precision than a wider interval, while an interval still represents uncertainty rather than a range containing a fixed proportion of individual participant values. These intervals are for the group estimates; they are not presented as confidence intervals for differences between groups.

Because the primary results are reported separately by arm, the intervals do not directly answer a comparison question. A formal comparison would ordinarily require an estimate of the between-group difference or a model relating dose to response, with its uncertainty and an analysis plan. No such primary comparison is reported in the registry record. General statistical principle: comparing separate confidence intervals is not a substitute for estimating and testing the contrast of interest.

How does the dose-finding approach fit the question?

The arm descriptions state that the propofol dose for the first patient was set separately for each ketamine group. Subsequent doses were to increase or decrease by a stated amount using the Dixon Up and Down method. In general, an up-and-down dose-finding design changes the next dose in response to the preceding participant’s observed response, concentrating observations around a response transition rather than assigning every participant to a fixed dose. This can be useful when the goal is to locate a dose associated with a specified response probability. The exact rules, response coding, and conduct of the procedure beyond the arm descriptions are not reported in the registry record.

The registry states an objective of determining the ED50, the dose associated with the specified response in 50% of subjects. In general, an ED50 is a dose-response quantity: it depends on the relationship between dose and response, not merely on an average dose. The record gives arm means and confidence intervals but does not report a fitted dose-response model or a separately calculated ED50 estimate. It is therefore important to distinguish the stated objective from the specific summaries that are posted.

What can the secondary comparisons establish?

For apnea duration, the record posts means and standard deviations by arm, as well as unadjusted pairwise comparisons against the 0 mg/kg ketamine group for two ketamine groups. A standard deviation describes variability among observations within a group; it is different from a confidence interval, which concerns uncertainty in an estimate. A mean difference gives the direction and size of a contrast on the outcome’s measurement scale. Its confidence interval describes uncertainty in that contrast, and an unadjusted p-value summarizes compatibility with a null comparison under the method used, without accounting for multiple testing.

The registry does not list reported analyses for the secondary outcomes. The posted unadjusted comparisons should not be interpreted as adjusted or prespecified confirmatory tests. General statistical principle: when several outcomes or contrasts are examined, the chance of at least one apparently notable result can increase unless multiplicity is addressed. Whether and how that issue was handled is not reported in the registry record.

How should sample-size illustrations be read?

The separate planning illustrations are explicitly based on observed effects, not on the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, and examine stated fractions of the observed effect for 80% or 90% power. These are prospective planning quantities: they describe participant requirements under those assumptions if a future study were planned to detect the specified effect. They are not observed power, do not show the power achieved by this trial, and do not establish that the trial was designed around those assumptions.

General statistical principle: planning estimates are sensitive to the effect size assumed. A smaller target effect generally requires a larger sample to detect under otherwise unchanged assumptions. The illustrations should therefore be treated as scenarios, not as a justification for the enrollment in this study. The registry does not report its own sample-size calculation, target effect, or design assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, but it does not report a statistical analysis plan describing how the family of outcomes or comparisons was handled. No multiplicity adjustment or testing hierarchy is reported. This matters because multiple tests can increase the chance of observing a nominally small p-value even when no underlying difference exists. General statistical principle: interpretation of multiple outcomes depends on which comparisons were planned and how the testing strategy accounts for them.

The primary outcome is presented as arm-level means and 95% confidence intervals. The registry record reports no inferential analyses for that endpoint, including no reported pairwise comparisons or trend test. The secondary apnea results include unadjusted comparisons for two groups against the 0 mg/kg group. Those p-values are not described as adjusted for other comparisons, and the record does not establish whether those tests were specified in advance. The other named secondary outcomes do not have posted numerical results.

Handling of missing data is not reported in the registry record. The record does not explain whether all randomized participants contributed to each outcome, how unavailable measurements were treated, or whether any imputation or sensitivity analysis was used. Analysis populations are also not described: there is no reported intention-to-treat, per-protocol, or other population definition. The posted arm counts and enrollment figure do not by themselves establish which participants were included in each analysis or why arm counts differ across outcomes.

These gaps do not invalidate the posted summaries, but they limit the ability to assess bias, reproducibility, and the strength of inferential claims. Without a reported analysis plan and transparent population and missing-data definitions, readers cannot determine whether the analyses followed prespecified rules or how robust the findings might be to alternative choices.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each ketamine group and zero deaths in each group. The numbers listed at risk for serious events are 14 for ketamine 0 mg/kg, 14 for 0.25 mg/kg, 13 for 0.5 mg/kg, and 14 for 1.0 mg/kg. These are the registry’s recorded counts; they do not show that the possibility of serious events has been ruled out.

The record also lists other adverse events affecting 7 participants in the 0 mg/kg group, 8 in the 0.25 mg/kg group, 10 in the 0.5 mg/kg group, and 11 in the 1.0 mg/kg group. The registry does not provide further detail about the event types, severity, timing, or whether events were considered related to study medication. No serious-event terms are listed.

These figures are descriptive and should be interpreted in light of the study’s limited enrollment and the absence of detailed event-level information. A zero count in a group is not proof that an event cannot occur, and counts of other events do not establish a causal relationship. The registry does not report additional safety analyses or a comparison testing differences between groups.

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

The posted primary results describe mean propofol doses associated with the movement-prevention endpoint in four ketamine groups. The reported mean is lowest in the ketamine 1.0 mg/kg group, while the intermediate-dose groups have similar means. The confidence intervals communicate uncertainty around those group estimates. This is a descriptive account of the posted data, not a statement that a particular regimen works or does not work.

The result does not establish a statistically significant difference between groups. No inferential analysis of the primary endpoint is reported, and the registry does not provide a fitted dose-response model or a reported ED50 estimate. The observed arm summaries therefore should not be equated with a definitive dose-response conclusion. Nor do they indicate whether any difference is clinically important: the registry does not report a threshold for clinical importance or contextual information to assess it.

The findings also do not establish comparative safety. Serious adverse event and death counts are zero in every listed group, while other adverse events are recorded. The available safety summary does not give event types or analyses capable of attributing events to a treatment. Secondary reporting is incomplete, with numerical results missing for named outcomes. This prevents a comprehensive interpretation across procedure-related events and recovery.

More broadly, the registry record does not report key elements needed to evaluate the statistical evidence in depth, including the analysis plan, missing-data methods, analysis populations, multiplicity handling, and the rationale for the enrollment target. Those details matter when moving from observed summaries to claims about reproducibility or generalizability. The appropriate conclusion is limited to the reported estimates, their stated confidence intervals, and the record’s identified gaps.

13. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a dose-finding objective and the summaries ultimately posted. The stated objective is to determine an ED50 for propofol in combination with several ketamine doses, while the primary results are arm-level means with confidence intervals. Those summaries show how the recorded mean dose varies across groups, but an ED50 is a dose-response quantity tied to a defined response probability. Recognizing the distinction prevents a descriptive mean from being mistaken for the target dose-response estimate.

The registry also describes an up-and-down dose-adjustment method. In general, response-adaptive dose allocation can concentrate observations around a response boundary, which is relevant to dose finding. However, interpreting such a design requires clear reporting of the response definition, dose rules, model or estimator, and uncertainty calculation. The available record does not report those details beyond the arm descriptions, nor does it post a model-based ED50 analysis. This illustrates why the method and estimand should be stated together.

Finally, the record demonstrates how reporting completeness shapes interpretation. Arm summaries and safety counts are available, but primary inferential analyses, several named secondary results, and important analysis details are not reported. Sample-size planning illustrations based on observed effects are not a substitute for the trial’s design justification. Separating descriptive results, confirmatory tests, and planning scenarios helps readers understand what each statistic can support—and where the evidence remains limited.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record constrain interpretation. The primary outcome is reported through group means and confidence intervals, but the registry does not post a formal primary comparison, a dose-response model, or an ED50 estimate. It is therefore not possible to assess the stated dose-finding target directly from the reported analysis. The endpoint description refers to preventing minimal or no movement, but the registry does not further explain how movement was assessed or classified.

The dose-finding procedure is described through starting doses and subsequent dose changes using the Dixon Up and Down method. The record does not provide additional details about implementation, the response rules used in practice, or how the final estimates and confidence intervals were obtained. The randomization and masking labels are reported, but the sequence generation, allocation concealment, and masking procedures are not described.

Reporting of secondary outcomes is partial. Apnea-duration results are posted, but numerical results are not reported for respiratory events during the procedure or side effects and complications during recovery. The posted secondary comparisons are unadjusted, and no multiplicity approach is described. The registry also does not explain whether all participants were included in each outcome analysis or how missing observations were handled.

The sample-size illustrations use observed effects and stated planning assumptions rather than documenting the trial’s own design calculation. The rationale for enrollment is not reported in the registry record. Finally, the record offers limited detail on participant characteristics and event-level safety information. These omissions restrict assessment of generalizability, precision, potential bias, and the completeness of the outcome picture.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ketamine and Propofol for Upper Endoscopy — NCT02295553.
• Registry record last updated 2019-06-10; status last verified 2019-03.
• Results first posted 2019-06-10.
• 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

NCT02295553 is a completed Phase 4, randomized, double-masked, parallel-group study sponsored by The Hospital for Sick Children, with enrollment of 56. It examined ketamine in combination with propofol for upper endoscopy in children. The primary outcome was propofol dose associated with preventing movement at endoscope insertion, reported as a mean with a 95% confidence interval for each ketamine group.

The posted primary means were 6.1 mg/kg, 4.5 mg/kg, 4.7 mg/kg, and 1.1 mg/kg across ketamine doses of 0 mg/kg, 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. No inferential primary analysis is reported. Numerical secondary results are posted for apnea duration, while other named secondary outcomes have no posted numerical results. The safety summary records no serious adverse events or deaths in the listed groups. Analysis-plan, missing-data, and multiplicity details are not reported in the registry record.