Evaluating the Hemodynamic Effects of Ketamine Versus Etomidate During Rapid Sequence Intubation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Hemodynamic Effects of Ketamine Versus Etomidate During Rapid Sequence Intubation (NCT03545503), a randomized phase 4 study. The primary outcome is Hemodynamic Effect as Measured by Systolic Blood Pressure Before and After RSI.

2. Clinical Question

3. Trial Design

This was a Phase 4 randomized controlled trial with a parallel-arm design. The registry record lists etomidate and ketamine as the two study drugs and reports enrollment of 428. It describes administration as a single intravenous push dose: 0.3 mg/kg for etomidate and 2 mg/kg for ketamine. The setting identified in the study summary is pre-hospital and emergency department rapid sequence intubation.

The masking entry is none, so the trial is recorded as not masked. The registry record does not explain whether participants, clinicians, outcome assessors, or data analysts were aware of treatment assignment, nor does it describe any safeguards against measurement or reporting bias. Allocation is listed as randomized, but the method used to generate or conceal assignments is not reported in the registry record. The record also does not state the allocation ratio.

The study is listed as completed. Its recorded start date is 2018-01-01, and its primary completion date is 2019-09-01. These dates describe the registry record and do not, by themselves, explain when analyses were conducted or when results were submitted.

The primary outcome is systolic blood pressure before and after rapid sequence intubation. The measurement window is defined as the change between vital signs taken 15 minutes prior to administration and vital signs up to 15 minutes after administration. Although the record identifies a mean and standard deviation as the outcome’s summary type, it does not include arm-level means, standard deviations, sample sizes for the primary analysis, or a numerical treatment comparison. It also does not report a statistical analysis plan, a sample-size justification, or details of interim analyses.

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: 98 did not meet inclusion criteria, 48 had incomplete sedative data, and 71 were excluded for other reasons

Overall Study

Reasons for not completing this period:

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 Hemodynamic Effect as Measured by Systolic Blood Pressure Before and After RSI, measured over The hemodynamic response will be measured by assessing the change in vital signs between 15 minutes prior to administration and vitals up to 15 minutes after the administration of the study drug..

The primary endpoint concerns change in systolic blood pressure from before to after administration of the study drug. The registry defines the timing as vital signs measured 15 minutes prior to administration and vital signs up to 15 minutes after administration. The outcome is expressed in mmHg, and the recorded summary type is a mean with standard deviation. A separate threshold definition identifies a significant hemodynamic response as a systolic blood pressure decrease of 20% or greater between the pre- and post-administration measurements.

As a general statistical point, a continuous measure such as systolic blood pressure can describe both the typical amount of change and variation among observations. Reporting a mean alone does not show how variable individual measurements were; a standard deviation describes that spread. A threshold can be useful for expressing how often changes meet a prespecified definition, but it does not convey the full distribution of the continuous measure. The two approaches answer related but different questions.

Blood pressure is directly aligned with the study’s stated objective of comparing hemodynamic effects around intubation. However, the registry record does not report the primary-outcome values, the number of observations contributing to the outcome, or a comparison between the randomized arms. It therefore does not allow readers to assess the direction, magnitude, or precision of the primary endpoint results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help translate observed measurements into estimates and quantify how much uncertainty surrounds those estimates. The record identifies the intended outcome and summary type, but does not report the primary-outcome analysis itself. The concepts below explain how such an analysis is generally interpreted; they are not a description of an unreported method used by this trial.

What does a mean summarize?

For a continuous outcome, the mean is the arithmetic average of the observed values in a group. In this study, the stated outcome is systolic blood pressure change around administration of the study drug. A mean change would describe the average change among observations included in the analysis, but would not show whether most observations were close to that average or whether the average was influenced by a smaller number of unusually large changes. The registry records the standard deviation as the measure of dispersion, but reports no mean or standard deviation for either arm.

The standard deviation describes the spread of observations around the mean. It is not the same as the uncertainty in the estimated mean: uncertainty also depends on how many observations contributed and on the analysis. The registry record does not report the number of participants with usable primary-outcome measurements or the arm-level summary statistics needed to interpret that spread.

What would a between-arm estimate mean?

A randomized comparison commonly focuses on an estimated contrast between treatment groups. For a continuous outcome, this might be a difference in average change, depending on the analysis plan. Such an estimate gives the direction and size of the comparison on the outcome’s scale. A confidence interval would express the range of values compatible with the data and analysis under the method’s assumptions. A narrow interval indicates greater precision than a wide interval; neither an estimate nor its interval alone establishes clinical importance.

No primary-outcome contrast or confidence interval is reported in the registry record. It is therefore not possible to describe a numerical difference or its precision. The record also does not say whether the intended comparison was based on change scores, post-administration values adjusted for baseline, or another method. Those methods can answer related questions but rely on different modeling choices.

How does the threshold relate to the continuous outcome?

The registry defines a significant hemodynamic response as a decrease in systolic blood pressure of 20% or greater between the pre- and post-administration measurements. In general, converting a continuous measure into a threshold category can make a particular event definition easier to communicate, but it discards information about how far observations fall from the threshold. Two observations on opposite sides of a cutoff may be similar in size, while two observations on the same side may differ substantially.

The threshold is a registry definition, not evidence that an event occurred or that the threshold was used in a particular statistical test. No arm-level counts for this endpoint, no risk estimates, and no analysis method for the threshold are reported. The registry record also does not explain how the paired pre- and post-administration readings were selected when measurements were available at more than one time.

Why does variation matter?

As a general statistical principle, the spread of observed values affects how precisely a group average or between-group contrast can be estimated. Greater variability tends to make a given amount of data less informative about the average. If measurements are clustered, repeated, or otherwise correlated, treating all observations as independent can also misrepresent uncertainty. The record describes a pre- and post-administration measurement window but does not report the number or timing of actual readings, or the method used to handle repeated values.

Some continuous outcomes may depart from the assumptions of simple normal-based methods. Analysts may consider distribution shape, outliers, or unequal variability between groups. This is general guidance, not a claim about the distribution in this study: no underlying values or arm-level summary statistics are reported. The registry record does not state whether transformations, robust methods, or model checks were planned or used.

What can a p-value tell a reader?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis under the assumptions of a statistical model. It does not give the probability that the null hypothesis is true, measure the size of an effect, or show whether an effect matters clinically. A p-value is most informative alongside an effect estimate and confidence interval. None of these primary-comparison statistics is reported in the registry record, so no significance claim can be assessed.

What is the role of planning calculations?

Planning calculations estimate how much information a future study might need for a chosen statistical objective and set of assumptions. The record describes a planning illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as stated fractions of the observed effect. Such calculations are illustrations, not evidence about the trial’s actual design rationale, and they are not observed power. The sample-size justification and the trial’s own planning assumptions are not reported in the registry record.

The registry outcome was not reduced to a single primary comparison for this analysis because it includes several categories or time points. Without a defined and reported estimate for the primary endpoint, a planning calculation based on that endpoint cannot be interpreted as a trial-specific design result. In general, power calculations depend on the chosen outcome, analysis, variability, allocation, and target effect; changing those assumptions changes the resulting planning estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure, but the primary endpoint description includes measurements before and after administration and a threshold definition for a decrease of 20% or greater. Multiple time points, outcome definitions, or analyses can create multiplicity: the more comparisons considered, the greater the chance that at least one appears noteworthy by chance if no adjustment or prespecification is used. This is a general concern, not a finding that multiplicity affected this trial. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or which analysis was designated for inference.

The record reports no primary-outcome analysis and does not state how missing measurements were handled. It does not provide the number of participants with available pre- and post-administration values, reasons for missingness, or whether any imputation or sensitivity analysis was planned or performed. Missingness can affect an estimate if the availability of measurements is related to the outcome or to treatment assignment. Without the relevant reporting, the extent and direction of any such effect cannot be assessed.

Analysis populations are also not described. The registry record does not say whether the intended analysis included all randomized participants, only those who received the assigned drug, or another defined group. The enrollment figure is not a substitute for the number included in the primary analysis. A transparent report would normally identify the population analyzed, exclusions, and the number contributing to each outcome; those details are not reported in the registry record.

These omissions limit interpretation of both statistical significance and precision. They do not establish that missing data or multiplicity problems occurred; they mean that the registry record does not provide information needed to evaluate those possibilities.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertension (0.5%).

The registry lists serious adverse-event counts of 0 among 194 at risk in the etomidate arm and 1 among 204 at risk in the ketamine arm. It lists other adverse-event counts of 117 among 194 at risk for etomidate and 111 among 204 at risk for ketamine. Deaths are listed as 0 in both arms. The registry also identifies hypertension at 0.5% among the top serious adverse-event terms. The record does not specify an arm for that term in the information, so it should not be assigned to an arm.

These entries are descriptive counts, not proof of a treatment effect or of causation. The registry record does not give definitions for serious and other adverse events, describe how events were collected, state the observation period, or provide a statistical comparison. It also does not explain whether the other adverse-event counts represent participants, events, or another reporting unit, so the counts should be read in the registry’s stated categories rather than reinterpreted.

Small differences in reported counts do not by themselves establish a reliable difference in risk. Interpretation depends on the event definitions, duration and completeness of follow-up, and the uncertainty around comparative estimates. No such comparative safety estimate or confidence interval is reported in the registry record. The zero death counts should likewise be read as registry entries, not as evidence that no deaths occurred outside the recorded follow-up or reporting scope.

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

The record establishes that a randomized Phase 4 study compared etomidate with ketamine during rapid sequence intubation and identified systolic blood pressure change as its primary outcome. It also states the doses, setting, measurement window, and threshold used to define a decrease of 20% or greater. These details clarify the question the study intended to address.

However, the registry record does not report numerical results for the primary endpoint or a statistical comparison between arms. It therefore does not show whether average systolic blood pressure change differed, how often the threshold response occurred, or how precise any between-arm estimate was. It is not possible to use the registry record to conclude that one study drug had a larger, smaller, or similar hemodynamic effect.

The posted safety counts offer descriptive information, but they do not establish that a treatment caused an event or that the arms differed in safety. The record does not report comparative safety estimates, event definitions, or the observation period. The serious adverse-event counts and death counts should be interpreted within those reporting limits.

More generally, a randomized design can strengthen a comparison when assignment, follow-up, measurement, and analysis are carried out and reported appropriately. The registry identifies randomization but does not describe its implementation or the analysis population. A design label alone cannot resolve uncertainty created by missing outcome results or missing methodological details.

Accordingly, the record documents the trial question and selected design features, but it does not provide enough outcome information to judge the magnitude or precision of the primary comparison. Absence of a numerical result in the registry is not evidence of no difference; it leaves the comparison unquantified in this record.

13. Why This Trial Matters Statistically

This trial raises a statistically focused question: how to characterize short-term changes in a continuous physiologic measure and compare them between randomized groups. The registry makes the intended measure and time window explicit, which is necessary for interpreting an outcome. It also defines a threshold response, illustrating how a continuous measurement can be reported both as an average change and as a categorized event.

Those summaries answer different questions. The continuous result would describe the average degree of change and its variability; a threshold count would describe how often a specified decrease was reached. Reporting both can be informative, but their interpretation depends on clear definitions and a prespecified analysis. Here, the registry record does not provide numerical results for either form of the primary endpoint, so the intended comparison cannot be assessed.

The record is also a reminder that randomization and outcome reporting are separate parts of evidence evaluation. Random assignment can support a fair comparison, but readers still need outcome estimates, uncertainty measures, and information about analysis populations and missing observations. The registry lists no analyses and does not describe these methods. The absence of those details limits the statistical conclusions that can be drawn even though the study design and treatment arms are identifiable.

Finally, the safety entries illustrate why raw counts need context. Definitions, follow-up, completeness, and comparative uncertainty all matter. Without that context, counts should not be turned into causal claims or broad judgments. For clinical researchers, this record underscores the importance of complete outcome reporting alongside trial registration: a clearly stated question is valuable, but an interpretable comparison requires the results and methods that connect measurements to conclusions.

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 principal limitation is that the registry record does not report a numerical result for the stated primary endpoint. There are no arm-level systolic blood pressure summaries, no between-arm estimate, and no confidence interval or p-value. The direction, magnitude, and precision of the primary comparison therefore cannot be assessed.

The record does not explain how the repeated measurements within the pre- and post-administration windows were selected or combined. It also does not report how the threshold definition was analyzed, how missing vital signs were handled, or how many observations contributed to the outcome. Those omissions prevent assessment of the endpoint’s operational details and analysis population.

Although allocation is recorded as randomized, the randomization method and allocation ratio are not reported. Masking is listed as none, but the record does not clarify who knew assignment or who measured and analyzed outcomes. The statistical analysis plan, sample-size justification, handling of multiplicity, and interim analysis plans are not reported in the registry record. These absences limit evaluation of potential bias and the role of prespecification.

The safety entries are also limited: definitions, follow-up duration, event-collection methods, and comparative analyses are not reported. The record’s enrollment figure does not identify how many participants contributed to each outcome. These limitations do not demonstrate that the trial was poorly conducted; they describe what cannot be evaluated from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating the Hemodynamic Effects of Ketamine Versus Etomidate During Rapid Sequence Intubation — NCT03545503.
• Registry record last updated 2021-11-26; status last verified 2021-10.
• Results first posted 2021-11-26.
• 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 completed, randomized, parallel-group Phase 4 trial comparing etomidate with ketamine for rapid sequence intubation in pre-hospital and emergency department settings. Masking is listed as none. The recorded doses are 0.3 mg/kg for etomidate and 2 mg/kg for ketamine, each as a single intravenous push. Enrollment is listed as 428.

The primary outcome is systolic blood pressure change, measured from 15 minutes before administration to up to 15 minutes after administration. A decrease of 20% or greater is defined as a significant hemodynamic response. No numerical primary-outcome results or statistical comparisons are reported in the registry record.

Safety entries list serious adverse-event counts, other adverse-event counts, and zero deaths in both arms. The record does not report the primary analysis population, missing-data methods, multiplicity approach, or a statistical analysis plan.