A Study to Determine if Caffeine Accelerates Emergence From Propofol Anesthesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Determine if Caffeine Accelerates Emergence From Propofol Anesthesia (NCT03360903), a randomized phase 4 study. The primary outcome is Waking Time - Time Between Terminating Anesthesia and Subject Opening Eyes..

2. Clinical Question

The clinical question is therefore a within-volunteer comparison of emergence after caffeine and after saline, rather than a comparison of separate groups of people. Randomizing the order was intended to reduce the possibility that a systematic order difference would be mistaken for a treatment difference. The record says the study was randomized and crossover. It describes the study as double-blind in the brief summary, while the registry’s masking field labels it triple-masked; that difference is not explained in the registry record.

The record describes a proposed investigation of whether findings from animal studies might also apply to humans. It does not report primary outcome measurements or an estimate of the difference in waking time. As a result, the registry record cannot answer whether the observed waking times differed between caffeine and saline sessions.

3. Trial Design

This was a randomized, placebo-controlled crossover study listed as Phase 4. The study was sponsored by the University of Chicago and was registered as completed. Its start date was 2018-01-02, and its primary completion date was 2018-12-31. Enrollment was 8.

In a crossover design, each volunteer is intended to receive both conditions at different times. Here, the two conditions were caffeine and saline placebo, each given in connection with propofol anesthesia. The arm descriptions specify two possible sequences: placebo followed by caffeine, or caffeine followed by placebo. A washout period was described between the sessions. The record does not report the washout duration or explain how its adequacy was assessed.

Random assignment to sequence can help prevent order from being systematically tied to one condition. Having each volunteer experience both conditions can also make the comparison less dependent on differences between people. These are general features of crossover designs, not evidence that the design successfully controlled order, period, or carryover effects in this study. No outcome data were collected and analyzed, so the record does not allow those issues to be assessed empirically.

The registry identifies the study as triple-masked, while the brief summary describes it as double-blind. The record does not explain which roles were masked or why those descriptions differ. It also does not report the randomization method, allocation concealment procedures, or a detailed statistical analysis plan. The record lists cognitive tests, bispectral index, mean arterial blood pressure, and heart rate among the secondary outcomes. It does not report results for those measures.

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.

First Intervention

Washout (2 Weeks)

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Due to technical problems during the study, data was not collected and analyzed.

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 Waking Time - Time Between Terminating Anesthesia and Subject Opening Eyes., measured over 15 minutes.

The primary endpoint was waking time, defined as the time between terminating delivery of anesthetic and the volunteer opening their eyes. The registry gives a timeframe of 15 minutes. This is a direct, time-based measure of emergence from anesthesia: it captures when the specified observable event occurred relative to the end of anesthetic delivery.

Using a defined event and a defined starting point makes the outcome interpretable. In general, a time-to-event measure describes how long it takes for an event of interest to occur. In this study, the event was opening the eyes, and the starting point was termination of anesthesia. The outcome was chosen to address the central question of whether emergence was faster following caffeine than following saline.

The record does not provide the observed waking times, a summary of their distribution, or a treatment comparison. It explicitly states that data were not collected and analyzed because of technical problems during the study. Consequently, there is no reported estimate of the caffeine–saline difference in waking time, and no assessment of its precision. The timeframe does not establish that outcome data were successfully obtained; the registry’s statement about technical problems is the relevant report of data availability.

The secondary outcomes include cognitive tests and physiological measures, but the registry does not report their results. The primary endpoint’s definition alone therefore describes what the study intended to measure; it does not establish what happened to volunteers’ waking times.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s design and the status of its outcome data determine what statistical conclusions are possible. Randomization, crossover structure, masking, outcome definition, and analysis are distinct parts of a trial. A design can be described in the registry even when the outcome needed to answer the research question is unavailable.

What does randomization contribute?

Random assignment of treatment order is intended to reduce systematic differences between the sequences. In a crossover study, a volunteer receives both conditions, but the order can still matter. For example, changes over time or effects that persist from an earlier session could complicate a comparison. Randomizing sequence is a design safeguard; it does not guarantee that order or carryover effects are absent. The registry does not report the randomization procedure or an analysis of sequence and period effects.

Why use a crossover comparison?

In general, crossover designs compare conditions within the same person. Stable characteristics that differ from one person to another are then less likely to explain a within-person difference than they would be in a comparison of separate groups. The design also requires careful attention to timing, treatment order, and possible carryover. The arm descriptions specify a washout period, but its duration and the evidence supporting it are not reported in the registry record. No outcome data are available to evaluate whether the intended within-volunteer comparison could be performed.

What does the endpoint represent?

The endpoint is time from terminating anesthetic delivery until opening the eyes. General statistical practice for time-to-event outcomes depends on whether event times are observed for all participants, whether any observations are censored, and how the analysis handles those features. The registry does not report the individual times, censoring information, or a statistical model. It states that primary outcome data were not collected and analyzed, so no time-to-event analysis can be evaluated.

What can masking tell readers?

Masking is intended to limit the influence of expectations or knowledge of treatment assignment on study conduct, measurement, and interpretation. The registry’s masking field says triple, while the brief summary says double-blind. The roles masked and the reason for the different descriptions are not reported. Masking cannot replace outcome measurement, and it cannot supply an effect estimate when the primary data are unavailable.

How should uncertainty be assessed?

In general, a treatment estimate describes the observed contrast, while a confidence interval describes uncertainty around that estimate. A p-value, when reported, summarizes how the observed data relate to a specified statistical null model; it does not by itself measure clinical importance or the probability that a treatment works. Here, the registry reports no primary outcome estimate, confidence interval, or p-value. There is therefore no inferential result to interpret for waking time.

Over-dispersion is a general concern when count data vary more than a simple statistical model expects; it can make standard errors too small if the extra variation is ignored. That issue cannot be assessed for this trial from the registry record. No primary outcome data or analysis are reported, and the record does not identify a count-based primary endpoint. It would be inappropriate to infer that a particular model or correction was used.

What do the planning illustrations mean?

Sample-size calculations are planning tools: they describe how many participants might be needed under stated assumptions to detect an effect at a chosen power and significance level. They are not observed power and do not demonstrate that a treatment effect was present. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They also say the effect to detect is a stated fraction of the observed effect, and distinguish the reporting basis for time-to-event outcomes from other outcomes.

For this record, those assumptions do not provide a trial result. The primary outcome was not collected and analyzed, so there is no reported observed waking-time effect to interpret as an estimate. Any planning illustration should be understood as conditional on its assumptions, not as a finding from the randomized comparison. The registry does not report the trial’s own sample-size justification or statistical planning rationale.

What can be concluded from the listed analysis status?

The record lists zero analyses. It does not report an analysis population, a method for handling missing outcomes, or adjustments for sequence, period, or carryover. These omissions matter because statistical methods are not interchangeable: the appropriate analysis depends on the design, the available observations, and the outcome’s distribution. Since the primary data were not collected and analyzed, the registry cannot show whether any proposed analysis was conducted outside the record or what its result might have been. The conclusions must remain limited to the information actually recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary waking-time outcome and several secondary measures, including cognitive tests, bispectral index, mean arterial blood pressure, and heart rate. When a study examines multiple outcomes, multiplicity can increase the chance of at least one apparently notable result arising by chance. General approaches include identifying a primary outcome in advance, specifying a testing hierarchy, or adjusting inference across tests. The registry record does not report a multiplicity strategy or a detailed statistical analysis plan.

The record lists zero analyses, and it says the primary outcome data were not collected and analyzed because of technical problems. It does not report results for the secondary outcomes. Consequently, there are no reported outcome tests to evaluate for multiplicity, and no basis for determining whether any adjustment was applied.

Missing-data methods are also not described. The registry does not report which outcome observations, if any, were missing at the volunteer or session level, or how missingness was handled in an analysis. It states that primary data were not collected and analyzed; that statement should not be replaced with an assumed imputation, exclusion, or other procedure.

The analysis population is not reported in the registry record. There is no reported account of which enrolled volunteers contributed to an outcome analysis, nor a description of how the crossover data would have been analyzed. These omissions prevent readers from assessing the relationship between enrollment, outcome availability, and analysis inclusion.

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 lists serious adverse events, other adverse events, and deaths separately for placebo and caffeine. For each condition, the record lists 8 at risk and zero affected for serious adverse events, 8 at risk and zero affected for other adverse events, and zero deaths. These are descriptive counts in the registry record.

A zero count means that no events in that category are recorded for the listed group; it does not establish that an event is impossible or that the conditions have identical safety profiles. In general, safety estimates are uncertain when based on limited observations, and the registry does not provide an uncertainty interval or a statistical comparison of the groups.

The study is described as crossover, so volunteers were intended to receive both conditions at different times. The adverse-event entries are organized by condition, but the record does not explain how event attribution, observation periods, or repeated exposure were handled. It also does not report definitions of serious and other adverse events or additional detail about monitoring.

These figures should be read as the safety counts recorded, not as proof of absence of risk. They do not provide evidence about the primary waking-time endpoint, which was not collected and analyzed.

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

The record documents a randomized crossover study designed to compare emergence after caffeine with emergence after saline placebo. Its primary endpoint was time from terminating anesthetic delivery until opening the eyes. The registry reports that technical problems prevented collection and analysis of the primary outcome data.

That means the posted record cannot establish the direction, size, or precision of a caffeine–saline difference in waking time. It does not show that caffeine accelerated emergence, and it does not show that caffeine failed to accelerate emergence. It also cannot demonstrate equivalence between caffeine and placebo. Equivalence requires an appropriate design, a prespecified margin, and sufficiently precise data; those elements are not reported.

The study’s intended secondary questions included cognitive performance and physiological measures. The registry lists those outcomes but does not report their results. The record therefore cannot support conclusions about whether caffeine changed cognitive test performance, bispectral index, mean arterial blood pressure, or heart rate.

The safety counts show zero recorded serious adverse events, zero other adverse events, and zero deaths for each listed condition. Those descriptive entries do not establish that risks are absent or that the conditions are equally safe. The record provides no inferential safety comparison or details needed to assess event ascertainment.

The trial’s completion status and its intended design should not be confused with an analyzable efficacy result. A completed study can still lack a reported primary outcome analysis. For this record, the most defensible interpretation is that the intended question remains unanswered in the posted results because the primary outcome data were not collected and analyzed.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it separates a study’s design from the evidence available to estimate its effect. Randomization and a crossover structure describe how the comparison was intended to work. They do not guarantee that an outcome was successfully measured, that an analysis was completed, or that a precise answer can be reported.

The primary endpoint was clearly framed as a time from a defined starting point to a defined event. That kind of operational definition is important: readers can understand what was meant by emergence and how it relates to the research question. But a well-defined endpoint still requires collected observations and an analysis. The registry states that technical problems prevented both for the primary outcome.

The record also illustrates why a missing result is not a null finding. Without an estimated contrast and a measure of uncertainty, readers cannot distinguish a small effect from a larger effect, or assess whether the data are compatible with different possibilities. A statement that no difference was found would overstate what the record reports.

Finally, the safety entries and planning assumptions answer different questions from the primary endpoint. Descriptive event counts do not establish the effect on waking time, and hypothetical sample-size planning does not substitute for observed outcome data. Keeping these distinctions clear helps prevent design details, safety summaries, or planning calculations from being mistaken for evidence about the central treatment comparison.

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 most consequential limitation is explicit: the registry says technical problems meant primary outcome data were not collected and analyzed. Without waking-time observations, there is no reported treatment estimate, uncertainty interval, or test of the primary question. The record also does not provide results for the listed secondary outcomes.

Enrollment was 8, and the study was designed as a crossover comparison. The registry does not report how many volunteers completed each session, whether every intended observation was obtained, or the characteristics of the enrolled volunteers. The record therefore does not permit assessment of completion, representativeness, or the availability of paired observations.

Some design details are unclear. The masking field labels the study triple-masked, while the brief summary calls it double-blind. The record does not explain the difference. It describes a washout period but does not state its duration. The randomization procedure and methods for addressing sequence, period, and possible carryover effects are also not reported.

The statistical analysis plan, analysis population, and missing-data procedures are not reported. The record lists zero analyses. It also does not report a multiplicity strategy for the primary and secondary outcomes. These absences limit assessment of how the study was intended to move from measurements to statistical conclusions.

The safety entries are descriptive and lack reported event definitions, monitoring details, and uncertainty estimates. They should not be interpreted as ruling out adverse events or establishing a comparative safety result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Determine if Caffeine Accelerates Emergence From Propofol Anesthesia — NCT03360903.
• Registry record last updated 2019-11-18; status last verified 2019-10.
• Results first posted 2019-11-18.
• 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, placebo-controlled crossover study of caffeine citrate during propofol anesthesia. It lists Phase 4, enrollment of 8, and the University of Chicago as sponsor. The listed start date is 2018-01-02, the primary completion date is 2018-12-31, and the status is completed.

The primary outcome was waking time, defined as time from terminating anesthetic delivery to opening the eyes, with a timeframe of 15 minutes. The registry states that technical problems meant these data were not collected and analyzed. No primary outcome result or analysis is reported. Secondary outcomes are listed, but their results are not reported. Safety entries list zero serious adverse events, zero other adverse events, and zero deaths for both placebo and caffeine.

The record describes a study designed to test whether caffeine accelerates emergence, but it does not provide data that answer that question.