Esmolol for Treatment of Perioperative Tachycardia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Esmolol for Treatment of Perioperative Tachycardia (NCT01208402), a randomized phase 3 study. The primary outcome is Percentage of Intraoperative Case Time With Heart Rate (HR) <60 or >80 Bpm.

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group phase 3 trial sponsored by Duke University. Its title identifies the study as an evaluation of esmolol for perioperative tachycardia. The registry describes the population as patients undergoing high-risk, non-cardiovascular surgeries and at risk for postoperative adverse ischemic outcomes. Enrollment was 76.

The two treatment groups were an esmolol infusion and oral long-acting beta blocker treatment. The latter was described as standard of care on the day of surgery. The esmolol infusion was described as beginning 30 minutes before induction and continuing for up to 12 hours postoperatively. The registry identifies the study as randomized and single-masked but does not report who was masked or how randomization was carried out.

The study began in 2010-09, with primary completion in 2013-07. Its status is terminated. A reason for termination is not reported in the registry record, so the status alone does not explain why the study stopped or whether the planned recruitment or follow-up was completed.

The registry lists six outcome measures and three posted secondary outcomes concerning time with systolic blood pressure below 95 mmHg during surgery and during two postoperative periods. The posted primary outcome concerns time with heart rate outside the target range during surgery. The registry record reports no analyses. It does not report detailed protocol information, a sample-size justification, or a full statistical analysis plan.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Three enrolled cases (1 in the oral long acting beta blocker group and 2 in the Esmolol infusion group) were excluded from calculations a priori because they received diltiazem, a calcium channel blocker which lowers heart rate, before the operation.

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 Percentage of Intraoperative Case Time With Heart Rate (HR) <60 or >80 Bpm, measured over Start of surgery to end of surgery, an average duration of 245 minutes.

The primary endpoint is the percentage of intraoperative case minutes during which heart rate was below 60 bpm or above 80 bpm. The target range is therefore 60 to 80 bpm, and time outside it can reflect either a heart rate that is too low or one that is too high. The outcome combines those directions into a single percentage rather than reporting separate measures for low and high heart rates.

Vital signs were measured from the start of surgery to the end, at intervals of 5 minutes or less. The stated timeframe is the whole surgical case, described as an average duration of 245 minutes. The endpoint expresses duration outside the target as a share of case minutes, allowing the amount of out-of-range time to be interpreted relative to each case's duration.

As a general statistical point, a time-based endpoint can capture repeated departures from a target across a monitoring period, rather than only a single measurement. Its interpretation depends on the chosen target, monitoring frequency, and definition of an excursion. The registry describes those definitions but does not report separate low-heart-rate and high-heart-rate results for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the group summaries describe?

The primary result is reported as a median with an inter-quartile range. The median is a measure of the center of a distribution: it is the middle value when observations are ordered. The inter-quartile range describes the central half of observations, bounded by the first and third quartiles. Here, the registry gives the median and the two endpoints of that range for each arm. This is a descriptive summary, not an estimate of the difference between the arms with quantified uncertainty.

In general, medians and inter-quartile ranges are useful when observations are unevenly distributed or when a few values could pull a mean away from the typical observation. They still do not show every feature of the distribution. They do not, by themselves, identify the number of participants at a particular value, explain the shape of the distribution, or establish whether groups differ beyond chance variation.

What does the endpoint measure?

The outcome is a percentage of case minutes outside the heart-rate target of 60 to 80 bpm. It counts periods below 60 bpm and above 80 bpm together. Because the endpoint combines both directions, its summary does not reveal whether out-of-range time was mainly attributable to low heart rate, high heart rate, or both. The registry says vital signs were measured at intervals of 5 minutes or less from the start to the end of surgery.

As a general matter, repeated monitoring can characterize duration outside a target more fully than a single reading. The result nevertheless depends on how the target is defined, how frequently measurements are taken, and how missing or irregular measurements are handled. The registry provides the target and measurement description, but details of missing-measurement handling are not reported in the registry record.

How should the comparison be understood?

Randomization is intended, in general, to make treatment groups comparable at the point of allocation, on average, so that outcome differences can be interpreted as comparisons of assigned strategies when the trial is conducted and analyzed appropriately. The registry labels the study randomized but does not describe sequence generation, allocation concealment, or adherence to assigned treatment. It also labels masking as single without specifying who was masked.

The posted results give separate arm summaries. They do not include a direct contrast, such as a difference in medians, or an uncertainty interval for a contrast. The presence of two group summaries does not substitute for an inferential comparison. In general, an analysis should reflect the outcome's distribution and the trial design, and should report an effect estimate together with its uncertainty. The specific statistical test or model used for this primary outcome is not reported in the registry record.

The primary endpoint summaries use 30 cases in the long-acting beta blocker arm and 26 in the esmolol arm. The registry explicitly notes that three enrolled cases were excluded a priori from the primary calculations after receiving diltiazem before surgery. The full analysis population, including how any other exclusions or missing measurements were treated, is not reported in the registry record.

What can be inferred from the spread?

The inter-quartile ranges are broad relative to the central values, indicating that the reported endpoint varied across participants in both arms. The ranges overlap. Overlap in descriptive ranges is not a formal test of a treatment difference, just as non-overlap would not by itself provide a complete analysis. A comparison requires an estimate of the contrast and its uncertainty, neither of which is posted for this outcome.

In general, variability can reduce the precision of an estimate, particularly when the sample is limited. Differences in case duration or clinical course can also affect a percentage-of-time endpoint, although the registry does not provide case-level information with which to investigate such patterns. It reports an average duration of 245 minutes, not a distribution of case durations.

What do the planning assumptions mean?

The registry's planning description characterizes the sample-size illustration as being based on the observed effect rather than the trial's own design. It states assumptions of a two-sided significance level of 0.05, equal allocation, a normal approximation, and detection of a stated fraction of the observed effect. The numerical planning results are not reported in the registry record. These planning illustrations are not observed power and should not be interpreted as the trial's original sample-size justification.

In general, sample-size planning estimates how many participants may be needed under specified assumptions about the effect, variability, allocation, and inferential threshold. Such calculations are conditional on those assumptions; they do not prove that a study is adequately powered for every outcome, nor do they establish the chance that a particular result is true. A planning calculation based on an observed effect is especially distinct from a prospective justification because the observed effect is known only after data have been collected.

Finally, a normal approximation is a modeling choice. In general, its suitability depends on the outcome distribution and the behavior of the estimator. The registry does not report enough detail to assess that choice for the primary endpoint or to reconstruct the planning illustration.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and identifies three posted secondary outcomes, all concerning the percentage of time with systolic blood pressure below 95 mmHg in perioperative periods. Numerical results for those secondary outcomes are not reported in the registry record. The registry also lists zero analyses. It therefore does not provide a complete set of analysis results with which to assess how the primary and secondary outcomes were handled statistically.

Multiplicity arises in general when several outcomes, time periods, or comparisons are examined. The more questions analyzed, the more important it is to know which were designated in advance and whether any method was used to account for multiple testing. Such methods and a prespecified analysis hierarchy are not reported in the registry record. Without that information, the risk of selective emphasis across outcomes cannot be evaluated from the posted record.

Missing-data handling is also not reported in the registry record. The primary outcome description does identify three enrolled cases excluded a priori from calculations because they received diltiazem before the operation: one in the oral long-acting beta blocker group and two in the esmolol infusion group. The reason is stated, but the registry does not report sensitivity analyses or the effect of these exclusions on the results. It does not describe whether other data were missing, how incomplete vital-sign measurements were treated, or whether any further exclusions occurred.

The registry does not identify the complete analysis population or state whether the primary comparison followed an intention-to-treat approach. It is therefore not possible to determine from the record whether participants were analyzed according to randomized assignment, treatment received, or another rule. These are important distinctions because excluding participants or observations after randomization can affect comparability between groups.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hemorrhage (3.6%), myocardial infarction (3.6%), intra-abdominal retroperitoneal abscess (3.2%), change in mental status (3.2%).

The registry reports serious adverse events in 2 of 31 participants in the long-acting beta blocker group and 2 of 28 participants in the esmolol group. It also reports other adverse events affecting 16 of 31 and 19 of 28 participants, respectively. These are counts of participants affected as recorded in the adverse-event summary; they do not provide event rates adjusted for exposure or time at risk.

The most frequently listed serious-event terms and their reported percentages are Hemorrhage, 3.6%; myocardial infarction, 3.6%; Intra-abdominal retroperitoneal abscess, 3.2%; and Change in Mental Status, 3.2%. The record does not provide enough context in these entries to assign each listed term to a particular treatment arm or to infer comparative risks from these percentages.

In general, adverse-event summaries are descriptive and require care in interpretation. A count does not establish that a treatment caused an event, and a small difference in counts is not, on its own, evidence of a safety difference. The registry does not report deaths in its adverse-event summary; death information is not reported in the registry record. No detailed exposure-adjusted comparison or statistical analysis of adverse events is reported.

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

The posted primary data describe the percentage of intraoperative case time outside the heart-rate target range in the two randomized groups. The reported medians are 39.2 for long-acting beta blocker treatment and 37.3 for esmolol, with broad inter-quartile ranges in both arms. These statistics characterize the observed participants included in the primary calculations; they do not by themselves quantify a reliable treatment effect.

The record does not report a confidence interval, p-value, or other inferential result for the primary comparison. It also does not report numerical results for the listed secondary blood-pressure outcomes. Consequently, the record does not establish whether the groups differed statistically, how precise a comparison would be, or whether any observed difference is clinically important. Statistical significance and clinical importance are distinct questions, and neither can be resolved from the posted medians alone.

The study's status is terminated, but a reason is not reported in the registry record. The trial enrolled 76 participants, and three cases were excluded from the primary outcome calculations after receiving diltiazem before surgery. These features should be kept in mind when considering how well the posted primary summaries represent the enrolled trial population.

In general, randomized comparisons can help estimate the effects of treatment strategies when allocation, follow-up, outcome measurement, and analysis are adequately described. The available registry entries provide the group summaries and some design information, but not the detailed analysis needed to establish a comparative effect. The findings should therefore be read as descriptive trial results rather than as a definitive estimate of the relative efficacy or safety of the two strategies. They do not support advice for an individual patient or a conclusion that either treatment works or does not work.

13. Why This Trial Matters Statistically

This trial illustrates why a randomized design and descriptive outcome summaries are not the same as a complete statistical comparison. Random allocation is an important design feature, but interpretation also depends on how participants were analyzed, how outcomes were measured, and how uncertainty around the treatment contrast was reported. The registry identifies randomization and posts medians by arm, yet does not report an inferential analysis for the primary outcome.

The endpoint also makes a useful statistical distinction visible: it combines low and high excursions into one measure of time outside a target. That produces a concise summary of overall out-of-range duration, but it can conceal whether the two directions contribute differently. Separate results would answer a different, more specific question; they are not reported for the primary outcome.

The primary calculations excluded three enrolled cases after preoperative diltiazem exposure. Their exclusion is described, making it possible to recognize that the outcome summaries do not use all enrolled cases. However, the record does not report sensitivity analyses or a complete account of the analysis population. This emphasizes the importance of transparent reporting of exclusions and analysis rules in randomized studies.

Finally, the record lists several outcome measures but posts only a limited set of numerical results and no analyses. Without outcome-specific estimates and methods, readers cannot assess precision, multiplicity, or the consistency of findings across outcomes. The trial is therefore a practical example of how the registry's design information, outcome definitions, and result summaries each contribute different pieces of evidence, while gaps in analysis reporting constrain what can be concluded.

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 record gives limited information for interpreting the primary comparison. It reports medians and inter-quartile ranges by arm but no treatment-effect estimate, confidence interval, or p-value. The registry lists zero analyses, and the statistical method used for the primary outcome is not reported in the registry record. The precision and inferential meaning of the between-group comparison therefore cannot be assessed.

Three enrolled cases were excluded from the primary calculations because they received diltiazem before the operation. Although the registry identifies the numbers excluded from each arm and the stated reason, it does not report sensitivity analyses or the full analysis population. The handling of incomplete monitoring data and any other exclusions is also not reported in the registry record.

The outcome aggregates time below and above the heart-rate target, so the primary summaries do not distinguish low-heart-rate excursions from high-heart-rate excursions. The registry describes measurements at intervals of 5 minutes or less but does not report case-level measurements or details of how irregular or missing readings were handled. It gives an average case duration of 245 minutes but does not describe variation in duration.

The trial was terminated, and the reason is not reported in the registry record. The record does not report a sample-size justification, detailed analysis plan, who was masked, or methods of randomization and allocation concealment. It lists secondary blood-pressure outcomes, but their numerical results are not reported in the registry record. These gaps limit assessment of the completeness and robustness of the posted findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Esmolol for Treatment of Perioperative Tachycardia — NCT01208402.
• Registry record last updated 2014-12-12; status last verified 2014-11.
• Results first posted 2014-11-19.
• 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

NCT01208402 is a randomized, single-masked, parallel-group phase 3 trial sponsored by Duke University. It enrolled 76 participants undergoing high-risk, non-cardiovascular surgery and compared an esmolol infusion with oral long-acting beta blocker treatment. The study began in 2010-09, reached primary completion in 2013-07, and is listed as terminated.

The primary outcome was the percentage of intraoperative case time with heart rate below 60 bpm or above 80 bpm. The posted medians were 39.2 for the long-acting beta blocker group and 37.3 for the esmolol group. The primary calculations excluded three cases that received diltiazem before surgery. The registry lists six outcome measures and three secondary blood-pressure outcomes, but reports zero analyses. A reason for termination, a detailed statistical plan, and inferential results for the primary comparison are not reported in the registry record.