Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients (NCT02203630), a randomized phase 4 study. The primary outcome is Maximum Heart Rate.

2. Clinical Question

The randomized pilot trial was designed to compare the two vasopressors in patients with septic shock. Its primary endpoint was maximum heart rate, reported in beats per minute. The registry's study aims also describe interest in tachyarrhythmias, heart rate, time spent in tachyarrhythmia, and related outcomes. However, the posted primary result is the arm-level maximum heart rate summary; the record does not provide a direct estimate of the treatment difference or a statistical test for that endpoint.

The registry reports maximum heart rate means of 96.7 beats/minute for phenylephrine and 108.6 beats/minute for norepinephrine. It gives a full range for each arm. These summaries describe the observed values but do not, by themselves, establish whether the arms differ beyond the uncertainty expected in a small study. The record does not report a confidence interval or p-value for the primary comparison.

3. Trial Design

This was a phase 4, randomized, parallel-group pilot trial comparing phenylephrine with norepinephrine in septic shock. The registry lists Vanderbilt University Medical Center as sponsor. It describes the study as open-label, and masking is listed as none. Thus, the registry does not describe masking of participants or study personnel to the assigned vasopressor.

The registry lists enrollment as 17. The arm-level results include 8 participants in the phenylephrine arm and 9 in the norepinephrine arm. These are the reported arm counts; the registry does not provide further detail about participant flow, withdrawals, or the number contributing to each outcome. The primary endpoint timeframe is up to 28 days.

The study start is listed as 2014-08 and primary completion as 2016-01. Its status is terminated. The reason for termination is not reported in the registry record, so the status alone cannot establish why the trial ended or whether it ended earlier than intended. The registry does not report a planned enrollment target or a rationale for the enrollment achieved.

The official title identifies the trial as a randomized controlled pilot trial. Pilot studies can provide preliminary estimates and help identify practical or measurement issues, but their results may be imprecise, particularly when the enrolled group is small. The registry record does not report a detailed protocol, allocation procedure, or statistical analysis plan. It also does not report whether any interim analyses were planned or performed.

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

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 Maximum Heart Rate, measured over Up to 28 days.

The primary endpoint is maximum heart rate, measured in beats per minute, over a timeframe of up to 28 days. It summarizes the highest recorded heart rate for participants in each arm during that stated period. A maximum captures peak values rather than the typical heart rate over time, and can therefore reflect brief episodes as well as sustained changes. It does not, on its own, identify when a peak occurred or why it occurred.

Heart rate is relevant to the trial's stated interest in tachyarrhythmias and the possible cardiac effects of vasopressors. Comparing maximum heart rate offers one way to describe the upper end of observed heart-rate experience in each randomized arm. It is distinct from counting arrhythmia events or measuring total time in arrhythmia, which are listed among the trial's other outcomes.

The registry reports a mean and a full range for each arm. A mean describes the central value across the reported observations, while the full range indicates the lowest and highest reported values. Neither is a measure of the precision of the mean. The registry does not report a standard deviation, standard error, or confidence interval for this endpoint. It also does not explain how maximum heart rate was selected or summarized when measurements were missing.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the design as randomized, parallel-group, and open-label, with no masking. Randomization is intended, in general, to make treatment assignment independent of participants' baseline characteristics on average. In a small trial, however, chance imbalances can still occur. The record does not describe the randomization sequence, concealment procedures, or baseline characteristics, so those aspects cannot be evaluated from the posted information.

What does the mean describe?

The primary endpoint is reported as a mean maximum heart rate for each arm. In general, a mean is the arithmetic average of observed values and can be influenced by unusually high or low observations. The registry also reports each arm's full range, which gives the observed minimum and maximum. A range is not a confidence interval: it describes observed values, not the uncertainty around an estimated mean. Because the record does not report a standard deviation or another measure of dispersion beyond the range, the spread and precision of the means cannot be characterized fully.

How should uncertainty be read?

In general, a confidence interval gives a range of values compatible with the data under a specified statistical procedure. Its width reflects uncertainty, which depends on factors such as sample size and variation. No confidence interval is reported for the maximum-heart-rate comparison. No p-value or formal test is reported either. Without those inferential quantities, the posted means and ranges cannot determine whether an apparent difference is distinguishable from sampling variation. A lack of a reported test is not evidence that the arms are equivalent.

The registry lists 8 participants in the phenylephrine arm and 9 in the norepinephrine arm. These are small groups for estimating an outcome that may vary across patients. As a general matter, a small study can produce unstable estimates, and observations at the extremes can have a noticeable influence on a mean or a maximum. The record does not provide enough distributional information to assess the influence of individual observations or to calculate a more precise uncertainty estimate.

What do the planning calculations mean?

Planning illustrations use assumptions different from an analysis of observed trial outcomes. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed using them. The registry does not report that they formed part of the trial's own design or sample-size justification. Any resulting sample-size figure is a planning illustration, not observed power and not a finding about the completed trial.

In general, power is the probability that a specified study design will detect an effect of a particular size under stated assumptions. It is not a measure of the probability that a result is true, and it cannot be inferred from a non-significant result. The registry does not report the trial's planned power or the assumptions used for its original enrollment target. It also does not report a target effect size or a sample-size justification. The planning illustrations should therefore be kept separate from the trial's reported results.

Why do outcome types matter?

The primary endpoint is a continuous measure, but the registry also lists outcomes involving arrhythmia events, use of treatments, ECG abnormalities, and days of mechanical ventilation. In general, continuous outcomes and event counts require different summaries and statistical models. Count outcomes can show over-dispersion when their variability exceeds what a simple count model assumes; if that occurs, a model that accounts for extra variability may be needed. This is a general methodological point only. The registry does not report the distribution of these outcomes or the model used to analyze them.

The record lists 37 outcome measures and indicates that results were posted for 29 secondary outcomes. It reports zero analyses. As a result, the posted record does not specify the analytical methods, effect estimates, or inferential procedures for these outcomes. It also does not describe adjustment for baseline covariates, repeated measurements, or other features that might matter for a particular outcome. No such method should be inferred from the arm summaries.

Finally, the registry does not report how missing measurements were handled, which analysis population was used, or whether analyses followed randomized assignment. These details can affect interpretation even when arm-level summaries are available. Without them, a reader cannot determine whether the summaries include all randomized participants, only participants with observed endpoint data, or another defined group.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 37 outcome measures and indicates results were posted for 29 secondary outcomes. It does not report an analysis plan or explain which outcomes were treated as primary or secondary for statistical testing beyond identifying maximum heart rate as the primary endpoint. It reports zero analyses. No multiplicity adjustment or hierarchy for testing multiple outcomes is described in the registry record.

When a study evaluates multiple outcomes or performs multiple statistical tests, the chance of at least one apparently notable result can increase. In general, prespecifying a primary outcome and controlling or otherwise addressing multiplicity can help make interpretation more disciplined. This is a general statistical consideration; the record does not establish whether such procedures were planned or used. The many listed outcomes should not be treated as independent confirmations of one another.

Missing-data handling is not reported in the registry record. The record does not state how many participants had a maximum-heart-rate measurement available, whether any measurements were excluded, or how missing values were handled. The arm counts reported with the endpoint do not, by themselves, describe participant flow or establish the analysis population.

The analysis population is also not reported. In particular, the record does not state whether the results were analyzed according to randomized assignment, according to treatment received, or under another rule. It does not describe deviations from assigned treatment or the handling of participants who discontinued. These omissions limit assessment of how the posted summaries relate to the randomized groups and how missingness might affect the comparison.

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 zero serious adverse events for the phenylephrine arm among 8 participants at risk and zero for the norepinephrine arm among 9 participants at risk. It also lists zero other adverse events in each arm, with the same arm-specific numbers at risk. These are the posted event counts; they should be read alongside the limited enrollment and not as proof that adverse events cannot occur.

The record also lists 2 deaths in the phenylephrine arm and 3 in the norepinephrine arm. It does not report the causes or timing of these deaths, or whether they were considered related to treatment. The death counts are separate entries from the adverse-event counts and should not be assumed to have been classified as treatment-related events.

The registry does not provide serious-event definitions, reporting windows, event-level descriptions, or additional detail about ascertainment. With limited enrollment, a zero count means no events were recorded in the posted results for that category; it does not establish absence of risk. These safety figures describe this trial record only and do not support a broader safety comparison.

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

The primary result describes maximum heart rate during a timeframe of up to 28 days, with arm-level means and full ranges. It provides a preliminary descriptive account of the observations recorded in this randomized pilot trial. The mean was 96.7 beats/minute for phenylephrine and 108.6 beats/minute for norepinephrine; the ranges were 65.0 to 132.0 and 57.0 to 153.0 beats/minute, respectively.

The result does not quantify the uncertainty around the difference between those means. No confidence interval, p-value, or formal analysis of the primary comparison is reported. The observed summaries therefore cannot establish whether the apparent difference is larger than would be expected from chance variation. They also cannot establish equivalence, because the record does not report an equivalence design or an equivalence analysis.

The result does not show that one vasopressor works better, is safer, or should be selected for a patient. The trial is small, open-label, and listed as terminated; its reason for termination is not reported in the registry record. The record also lacks detail about missing outcomes, participant flow, and the analysis population. Those limitations make it difficult to evaluate the completeness and robustness of the comparison.

The trial's listed aims and secondary outcomes extend beyond maximum heart rate, including arrhythmia-related measures and other clinical events. Their presence in the registry does not establish what those outcomes showed or whether differences between arms were assessed. The registry indicates that results were posted for 29 secondary outcomes but reports zero analyses, so no inferential interpretation of those outcomes is available from the record.

The most defensible conclusion is narrow: the registry reports descriptive maximum-heart-rate values for the two randomized arms, with broad ranges and limited enrollment. The record does not provide the analysis and precision information needed to draw a firm statistical conclusion about a treatment effect.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it illustrates the difference between a randomized design and a conclusive treatment comparison. Randomization is a valuable design feature, but randomization alone does not guarantee precise estimates, particularly when enrollment is limited. Here, the registry reports arm-level means and ranges but no confidence interval, p-value, or formal analysis for the primary endpoint.

The study is identified as a pilot trial, and the posted primary endpoint is a maximum value rather than an average over time. Those choices matter for interpretation: a peak measurement can be influenced by brief extreme observations, while a mean can obscure variation between participants. Reporting a range adds context about observed extremes, but it does not replace a measure of uncertainty around the comparison.

The record also highlights why outcome multiplicity and analysis transparency matter. It lists many outcome measures and reports posted results for secondary outcomes, while providing no analyses. Without a documented analysis plan or inferential methods, readers cannot assess how the outcomes were prioritized, whether multiple testing was addressed, or how missing observations were handled.

Finally, the terminated status and absent reason for termination underscore the importance of trial-completion context. Status alone is not an explanation, and it does not establish a source of bias. It does signal that interpretation depends on details the record does not report, such as participant flow and the reasons the trial ended. Together, these features make the record useful for understanding descriptive reporting and its limits, rather than for establishing a precise comparative effect.

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 trial-specific limitations constrain interpretation. Enrollment is listed as 17, and the endpoint results include 8 participants in the phenylephrine arm and 9 in the norepinephrine arm. The small groups limit the amount of information available for estimating arm differences and make the summaries potentially sensitive to individual observations. The record does not provide confidence intervals or another uncertainty measure for the primary endpoint.

The study was open-label, with masking listed as none. The registry does not describe whether knowledge of assignment could have influenced measurement, care, or outcome recording. Maximum heart rate is a quantitative endpoint, but the record does not provide measurement procedures, baseline heart rates, or details about the timing and frequency of measurements.

The status is terminated, and the reason is not reported in the registry record. Participant flow, withdrawals, protocol deviations, and missing-data handling are also not reported. The record does not identify the analysis population or state how observations were included in the arm-level summaries. These omissions prevent assessment of whether the posted results reflect all randomized participants.

The registry lists numerous outcomes, but reports zero analyses. It does not describe a statistical analysis plan, multiplicity procedures, or models for the various outcome types. It also does not report a sample-size justification for the trial itself. The available planning assumptions are illustrations, not confirmation of the original design rationale. These gaps leave the descriptive arm summaries as the main basis for interpreting the primary result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients — NCT02203630.
• Registry record last updated 2018-06-13; status last verified 2018-05.
• Results first posted 2018-06-13.
• 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

NCT02203630 is a phase 4, randomized, open-label, parallel-group pilot trial sponsored by Vanderbilt University Medical Center. It compared phenylephrine with norepinephrine as the primary vasopressor for septic shock. The registry lists enrollment as 17, a study start of 2014-08, primary completion of 2016-01, and status as terminated.

The primary endpoint was maximum heart rate in beats per minute over up to 28 days. The posted means were 96.7 for phenylephrine and 108.6 for norepinephrine, with full ranges of 65.0 to 132.0 and 57.0 to 153.0, respectively. The record reports no inferential analyses for the primary comparison and does not provide a confidence interval or p-value. The reason for termination, missing-data handling, and analysis population are not reported in the registry record.