Esmolol or Nitroglycerin Infusion for Blood Pressure Control Prior to Cardiopulmonary Bypass (CPB) in Cardiac Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Esmolol or Nitroglycerin Infusion for Blood Pressure Control Prior to Cardiopulmonary Bypass (CPB) in Cardiac Surgery (NCT01212874), a randomized na study. The primary outcome is Diastolic Blood Pressure Excursions Beyond Predetermined Lower Limits, Normalized Per Hour.

2. Clinical Question

The clinical question concerns blood pressure control during a defined phase of cardiac surgery, not blood pressure across the entire operation or after cardiopulmonary bypass begins. Both groups received an infusion intended to control hypertension in that interval. The registry describes the study as a randomized, controlled trial and identifies hypertension as the condition of interest.

The endpoint focuses on excursions below predetermined lower limits, rather than simply reporting a blood pressure at a particular time. Its description is based on the area under the curve for those excursions, normalized by prebypass hour. The registry record does not state the lower limits themselves, how they were selected, or what magnitude of difference would be considered clinically important. Those omissions limit how specifically the research question can be interpreted.

3. Trial Design

The registry record describes a randomized, controlled, open-label, prospective trial with a parallel design. Participants were assigned to esmolol or nitroglycerin infusion for control of hypertension during cardiac surgery, from anesthesia induction until initiation of cardiopulmonary bypass. Because masking was listed as none, treatment assignment was not masked. The record does not describe the randomization sequence or allocation-concealment procedures.

The listed enrollment is 70. The primary-outcome results include 11 participants in the esmolol group and 10 in the nitroglycerin group. The endpoint description states that data capture failure lost data from 2 treated patients in each group, who were excluded from analysis. These outcome counts should not be treated as the full enrollment or as a complete account of participant flow: a detailed flow of enrollment, assignment, follow-up, and analysis is not reported in the registry record.

The registry lists the study status as completed, with a start date of 2010-12 and a primary completion date of 2014-06. The phase is recorded as NA. The sponsor is Loma Linda University. The record describes the trial as investigator initiated and sponsored, but does not give further details about conduct or oversight.

The posted primary outcome is diastolic blood pressure excursions beyond predetermined lower limits, normalized per hour. Its stated timeframe runs from anesthesia induction to initiation of cardiopulmonary bypass, described as an average of 5 hours. The record also lists systolic hypertension as a secondary outcome. It does not provide enough information to reconstruct the full protocol or to determine whether other outcomes were measured but not posted.

The safety results list 35 participants at risk in each group. Those safety counts differ from the participant counts listed for the primary outcome, and the registry record does not explain how the analysis populations relate to one another. No explanation should be inferred from the difference in those counts 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: Data capture failure lost data from 2 treated patients in each group; these were thus excluded from analysis.

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 Diastolic Blood Pressure Excursions Beyond Predetermined Lower Limits, Normalized Per Hour, measured over Participants were followed from Anesthesia Induction to Initiation of Cardiopulmonary Bypass, an average of 5 hours.

The primary endpoint is the area under the curve of diastolic blood pressure excursions beyond predetermined lower limits, normalized per prebypass hour. It is expressed in mmHg*min/prebypass hour. The measurement period begins at anesthesia induction and ends at initiation of cardiopulmonary bypass; the record describes this as an average of 5 hours.

An area-under-the-curve measure can combine the depth and duration of excursions rather than capturing only a reading at a single time. Normalizing by prebypass hour expresses the recorded burden relative to the time in that period. General: such an endpoint can be useful when the duration of observation varies, because a per-time measure may make exposure over different observation intervals more comparable. The registry does not describe whether or how the actual observation duration varied among participants.

The record summarizes the endpoint using a median and a 95% confidence interval for each treatment group. It does not specify the predetermined lower limits, the detailed calculation procedure, or whether any other data processing was applied. Those details matter for reproducing the endpoint and understanding exactly which blood pressure readings contribute to it.

Using excursions beyond lower limits makes the outcome a measure of a particular pattern of blood pressure, rather than a general measure of hypertension. The registry does not state why this endpoint was chosen, whether it was designated as the primary endpoint before enrollment, or what difference would be clinically meaningful. The results therefore describe this recorded measure but do not, by themselves, establish how it relates to broader clinical outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a median and a 95% confidence interval for the primary endpoint in each group, together with a two-sided t-test p-value for the comparison. It does not report the test statistic, degrees of freedom, a contrast estimate, or a confidence interval for the contrast. Those omissions constrain what can be reconstructed about the analysis.

What does a median describe?

General: the median is a measure of the center of a distribution. It is the value at the midpoint when observations are ordered, and it is less directly influenced by extreme observations than the arithmetic mean. A median describes the distribution's center; it does not convey how widely individual observations vary. The registry record does not provide participant-level outcome data or a separate measure of spread for the primary endpoint.

The reported group medians are 97.9 for esmolol and 45.6 for nitroglycerin, in mmHg*min/prebypass hour. These summaries describe each group's endpoint values. A difference between the reported medians is not the same thing as a reported median treatment effect, and no such treatment-effect estimate is posted.

What does a confidence interval express?

General: a confidence interval gives a range of values compatible with the data under a specified statistical procedure and its assumptions. Its width reflects statistical uncertainty in the estimate, while its interpretation depends on the interval method and the target quantity being estimated. A 95% confidence interval around a group summary is not automatically an interval for a contrast between groups.

The registry gives 95% confidence intervals for the group summaries: 47.7 to 181.4 for esmolol and 21.0 to 93.9 for nitroglycerin. It does not identify the method used to calculate these intervals. Nor does it report a confidence interval for the treatment contrast. The intervals should therefore be read as uncertainty ranges attached to the posted group summaries, not as a direct estimate of the uncertainty in the comparison.

How should the t-test be read?

The reported method is a two-sided t-test, with p=0.21. General: a two-sided test considers departures from the null in either direction. A t-test is commonly used to compare means under assumptions about the sampling distribution and, depending on the version, variance structure. The registry does not state which version was used, whether assumptions were assessed, or how the test was reconciled with the displayed median summaries.

A p-value is conditional on the null hypothesis and statistical model used for the test. General: it is not a measure of the probability that a treatment has no effect, nor is it a measure of the probability that the result occurred by chance in an unrestricted sense. It also does not indicate the magnitude of a difference. A numerical estimate and its uncertainty are needed to describe the size and precision of a contrast.

The listed outcome distributions may be important to method choice, but the registry does not report participant-level data or distributional diagnostics. General: skewness, outliers, and unequal variability can affect how well some methods describe or compare data. A median may be useful when a distribution is asymmetric, but the appropriate comparison method depends on the analysis question and assumptions. No conclusion about the actual distribution or test adequacy can be drawn from the record alone.

Why can over-dispersion matter?

General: over-dispersion occurs when observed variability is greater than a statistical model expects. If a method assumes less variability than the data actually contain, standard errors can be too small and confidence intervals too narrow, which may make evidence appear more precise than it is. Conversely, methods that account for additional variability can produce wider uncertainty estimates. The registry record does not report a model for the endpoint, a dispersion assessment, or an over-dispersion adjustment. There is no basis to claim that over-dispersion was present or that any particular correction was used.

What does normalization by time contribute?

The endpoint is normalized per prebypass hour and the observation period is described as an average of 5 hours. General: a rate-like measure can account for differing exposure durations when the amount accumulated depends on time at risk or time under observation. That interpretation depends on how the measure was constructed and on whether a per-time rate is appropriate for the underlying process. The registry describes the endpoint as normalized per hour but does not provide the detailed computation or participant-specific observation times.

How do planning calculations differ from trial results?

The sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration considers effects expressed as fractions of the observed effect. General: planning calculations ask how many participants might be needed under specified assumptions to detect a target effect with a chosen power. They are conditional on those assumptions and are not a description of what was observed in the trial.

Such planning illustrations are not observed power. Observed power is not a substitute for an effect estimate and its confidence interval, and calculations based on an observed effect can be especially dependent on the estimate used. The registry record does not state that these planning assumptions were the trial's original design assumptions. It does not report the protocol's sample-size justification or planned power.

The analysis details beyond the named test are not reported in the registry record. The record does not give an analysis population definition beyond the stated exclusions for data capture failure, a missing-data method, a prespecified model, or a description of any interim analysis. Those methods cannot be inferred from the group summaries or p-value.

10. Analyses Reported by the Sponsor

The registry reports the sponsor's comparison as a two-sided t-test with p=0.21. It gives group medians and 95% confidence intervals, but no numerical estimate or confidence interval for the between-group contrast. The registry record does not provide enough information to independently reproduce that test from the posted summaries: medians and their confidence intervals do not contain all the participant-level information needed to reconstruct a t-test.

No recalculated comparison is available in the record for this endpoint. In particular, no unadjusted re-calculation of the contrast or its uncertainty is reported. The sponsor's result should therefore be presented as the reported analysis, not replaced with a derived estimate from the group summaries. The registry does not identify the t-test variant or explain how the method relates to reporting medians.

No discrepancy is flagged in the registry record. That does not add information about the analysis assumptions or resolve the absence of a contrast estimate. The reported p-value remains a test result, not an effect size, and it does not show the magnitude or precision of the difference between groups. A fuller reading would require the contrast estimate, its confidence interval, and enough methodological detail to understand how they were obtained.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists systolic hypertension as a secondary outcome and reports 2 outcome measures and 2 analyses. It does not explain how those entries correspond to particular endpoints or comparisons. The record does not describe a prespecified hierarchy of outcomes, an adjustment for multiple comparisons, or a plan for controlling the chance of false-positive findings across analyses. Whether multiplicity was addressed is therefore not reported in the registry record.

General: when several outcomes or comparisons are examined, the chance of observing an apparently unusual result can increase if each is assessed without accounting for the others. Adjustment methods and prespecified outcome hierarchies are ways to address that issue, but they involve choices about which results are confirmatory and how to interpret them. The record does not contain enough information to determine whether such choices were made in this trial.

For the primary endpoint, data capture failure lost data from 2 treated patients in each group; the record says these patients were excluded from analysis. The analyzed counts were 11 for esmolol and 10 for nitroglycerin. The registry does not report the reasons for data capture failure in more detail, whether the missing outcome information was related to blood pressure values, or whether missingness differed in relevant ways between participants.

The record does not describe imputation, sensitivity analyses, or another method for addressing missing primary-outcome data. General: excluding participants with missing outcomes can be unbiased under some conditions, but can distort a comparison if the chance of missingness is related to treatment or outcome. The registry does not provide information to assess those conditions.

The safety results list 35 participants at risk in each group, whereas the primary-outcome analysis counts are smaller. The registry record does not explain these analysis populations or give a participant-flow account that would reconcile them. It also does not state whether the primary analysis followed an intention-to-treat principle, whether participants were analyzed as randomized, or whether any per-protocol analysis was conducted. These analysis-population details are not reported in the registry record.

12. 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.

The registry lists 35 participants at risk for serious adverse events in each group. It reports 0 affected participants in the esmolol group and 0 in the nitroglycerin group. For other adverse events, the record also lists 35 participants at risk in each group and 0 affected participants in each group. No top serious adverse event terms are listed.

These figures describe the posted safety counts; they do not establish that no adverse events occurred outside the categories or reporting period represented by these entries. The record does not explain the adverse-event collection method, the observation period for safety, or how events were attributed to treatment. It also does not give event-level details.

Deaths are recorded as null for both groups, so death counts are not reported in the registry record. Null should not be read as zero. The safety counts should also be kept distinct from the primary-outcome analysis counts, because the registry does not explain the relationship between those populations. These entries do not provide a basis for concluding that one infusion is safer than the other.

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

The primary-outcome results describe diastolic blood pressure excursions beyond predetermined lower limits during the period from anesthesia induction to initiation of cardiopulmonary bypass. The posted medians were 97.9 mmHg*min/prebypass hour for esmolol and 45.6 mmHg*min/prebypass hour for nitroglycerin. The registry also reports a two-sided t-test p-value of 0.21. Together, these registry entries describe the reported group summaries and test result, but not the magnitude and precision of a treatment contrast.

The record does not report a numerical contrast estimate or a confidence interval for that estimate. Without those quantities, readers cannot directly assess the range of treatment differences compatible with the analysis. The p-value alone cannot tell whether a difference is large or small, nor can it establish clinical importance. The registry does not state a threshold for a clinically meaningful change in the endpoint.

The endpoint is a measure of excursions below predetermined lower limits, normalized per prebypass hour. It is not a direct report of all blood pressure behavior during surgery, and it is not itself a patient-centered clinical outcome. The record does not report how the endpoint relates to later complications or other outcomes that might matter to patients.

The primary analysis excluded data from 2 treated patients in each group because of data capture failure. That loss of outcome data and the limited analyzed counts should inform interpretation. The registry does not describe whether missingness could have affected the results, or whether sensitivity analyses were performed.

The results do not establish a general conclusion about blood pressure control in other surgical settings, other populations, or periods outside the specified prebypass interval. The record describes a particular randomized trial and treatment comparison, but does not provide enough protocol detail to assess every design and analysis decision. These limitations apply alongside the fact that treatment assignment was open label and the reported comparison does not include a contrast confidence interval.

General: a randomized comparison can help assess differences between assigned groups, but its interpretation still depends on outcome measurement, missing data, analysis choices, and precision. The posted findings should therefore be read as a report of the measured endpoint in the analyzed participants, not as a definitive estimate of broader clinical benefit or harm.

14. Why This Trial Matters Statistically

This trial is statistically informative because its primary endpoint is not a single blood pressure reading. It is based on the area under the curve for diastolic excursions beyond predetermined lower limits and is normalized per prebypass hour. That structure raises practical questions about how repeated measurements were combined, how the lower limits were defined, and how observation time was handled. The registry gives the broad endpoint description but not the detailed calculation procedure.

The record also illustrates why group summaries and comparison estimates serve different purposes. Medians with confidence intervals describe each group's endpoint summary. A test p-value addresses a statistical comparison under a test's assumptions. A contrast estimate with its own confidence interval would directly describe the size and precision of the difference, but the registry does not report one.

The analysis population merits attention. Data capture failure led to exclusion of 2 treated patients from each group, while the reported primary-outcome counts are 11 and 10. The safety counts are 35 per group, and the registry does not explain how these populations relate. Making those distinctions explicit is important when assessing what data underpin each result.

The record names a t-test while presenting medians as the primary summaries. That combination does not by itself show that an error occurred, but it leaves the relationship between the displayed summaries and the test unclear. Details of the test variant, assumptions, and analysis plan would help readers understand the comparison.

Finally, the record lists a secondary outcome but does not describe multiplicity handling or broader analysis plans. These absences do not negate the posted results; they define the limits of what can be inferred from the registry entry. General: careful interpretation depends not only on the p-value, but also on the endpoint definition, data completeness, analysis populations, effect estimate, and uncertainty.

15. 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 registry does not define the predetermined lower limits used in the primary endpoint or state how those limits were selected. It describes an area-under-the-curve measure normalized per prebypass hour, but does not detail the computation, the blood pressure measurement schedule, or any data-processing rules. These omissions limit reproducibility and make it harder to assess exactly what the endpoint represents.

The primary outcome is reported as a median with a 95% confidence interval for each group, while the comparison method is identified as a two-sided t-test. The record does not explain the test variant, the estimand tested, or the relation between that test and the median summaries. It also does not post a contrast estimate or confidence interval for the comparison, limiting assessment of effect size and precision.

Data capture failure resulted in the exclusion of 2 treated patients in each group from the primary-outcome analysis. The registry does not report further details about the missing data, how missingness was assessed, or whether sensitivity analyses were done. The record also does not provide a participant flow that explains the primary-outcome counts in relation to enrollment or the safety counts.

The trial was open label. The registry does not describe any procedures intended to reduce the influence of unmasked treatment assignment on measurement or analysis. It also does not report the randomization sequence, allocation-concealment methods, sample-size justification, interim analyses, detailed analysis plan, or multiplicity approach. These items are not reported in the registry record and should not be inferred.

Finally, the listed primary endpoint is specific to blood pressure excursions before cardiopulmonary bypass. The record does not report a clinically meaningful threshold or provide a result for the listed systolic hypertension secondary outcome in the registry record recorded for this analysis. The posted information therefore supports a focused description of the primary endpoint, but not a broader account of clinical outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Esmolol or Nitroglycerin Infusion for Blood Pressure Control Prior to Cardiopulmonary Bypass (CPB) in Cardiac Surgery — NCT01212874.
• Registry record last updated 2019-03-01; status last verified 2019-02.
• Results first posted 2016-08-17.
• 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.

19. Record Summary

The registry record describes a completed, randomized, controlled, open-label, parallel-group trial of esmolol versus nitroglycerin infusion for control of hypertension between anesthesia induction and initiation of cardiopulmonary bypass during scheduled cardiac surgery. Listed enrollment is 70; the study start date is 2010-12, and the primary completion date is 2014-06. The phase is listed as NA.

The primary endpoint was diastolic blood pressure excursions beyond predetermined lower limits, measured as an area under the curve and normalized per prebypass hour. The group medians were 97.9 for esmolol and 45.6 for nitroglycerin, in mmHg*min/prebypass hour, with respective 95% confidence intervals of 47.7 to 181.4 and 21.0 to 93.9. The reported two-sided t-test p-value was 0.21.

Data capture failure led to the exclusion of 2 treated patients in each group from the primary-outcome analysis. The registry does not report a contrast estimate or confidence interval, detailed missing-data methods, or a full account of analysis populations. It lists systolic hypertension as a secondary outcome and reports 0 affected participants for serious and other adverse events in groups of 35 at risk; death counts are not reported.