This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Esmolol Infusion for Patients With Septic Shock and Persistent Tachycardia (NCT02841241), a na phase 2 study. The primary outcome is Organ-failure-free Days.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02841241 |
| Phase | Phase 2 |
| Condition | Septic Shock |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 7 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Intermountain Health Care, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with septic shock and persistent tachycardia after adequate intravenous volume expansion. The registry record reports enrollment of 7.
Intervention
Esmolol infusion, started without a bolus and slowly titrated upward under a protocol, with a target heart rate of 80-90/min.
Comparator
There was no concurrent control group. The study is registered as single group, and allocation is listed as NA; it is not a randomized comparison.
Primary question
At day 28, what was the distribution of organ-failure-free days, a score that combines survival with days without vasopressor therapy, mechanical ventilation, or renal replacement therapy?
This was a prospective roll-in study, not a trial designed to estimate a treatment contrast against another assigned group. Its stated purpose was to assess the adequacy and efficiency of study protocols for an anticipated main ECASSS study, which has a separate ClinicalTrials.gov entry. The registry record does not report numerical results for the primary outcome, so the distribution of day-28 scores cannot be described from this record.
Secondary outcomes named in the record are all-cause mortality, peak serum high-sensitivity troponin, left ventricular global longitudinal strain at 24 hours, and development of heart block. Their registered presence identifies outcomes of interest, but does not establish what was observed. Numerical results and analysis details for these outcomes are not reported in the registry record.
3. Trial Design
The registry identifies NCT02841241 as a phase 2, completed, prospective, single-group roll-in study sponsored by Intermountain Health Care, Inc. Its recorded start was 2016-04 and its primary completion was 2017-03. Enrollment was 7. The study title concerns esmolol infusion in patients with septic shock and persistent tachycardia; the official title describes it as a roll-in study of esmolol to control adrenergic storm in septic shock.
All participants were assigned to the Esmolol group as described in the registry. The infusion was started without a bolus, slowly titrated upward according to protocol, and had a target heart rate of 80-90/min. Allocation is listed as NA, masking as none, and the model as single group. Thus, the record does not describe random assignment, blinding, or a concurrent control arm. The study should be read as a protocol roll-in rather than a like-for-like comparison of treatment groups.
The stated purpose was to assess whether study protocols were adequate and efficient for an anticipated main ECASSS study. That main study was to have a separate registry entry. This context matters: the roll-in's stated objective is about protocol preparation, not a definitive estimate of comparative treatment effects.
The registry lists eight outcome measures and zero analyses. The primary outcome is organ-failure-free days at day 28; the listed secondary outcomes include mortality, a cardiac biomarker, a cardiac imaging measure at 24 hours, and heart block. Numerical outcome results and details of the statistical analysis are not reported in the registry record. The protocol, eligibility criteria, treatment adherence, and study-specific sample-size justification are also not reported in the registry record.
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
| Stage | Esmolol |
|---|---|
| STARTED | 7 |
| COMPLETED | 7 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | Esmolol |
|---|---|---|
| Participants analysed | 7 | |
| Age, Continuous | years | 46 (SD 19) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 6 |
| Race (NIH/OMB): More than one race | Participants | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 7 |
| Admission APACHE (Acute Physiologic Assessment and Chronic Health Evaluation) II | Units on a scale (0-100) | 28 (SD 8) |
6. Primary Endpoint
The registry lists the primary outcome as Organ-failure-free Days, measured over Day 28.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | units on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is organ-failure-free days at day 28, reported as a median with an interquartile range. It counts calendar days on which a patient receives none of vasopressor therapy, mechanical ventilation, or renal replacement therapy. The score also incorporates death: death on or before day 28 is assigned -1, while a score of 28 represents reaching day 28 without any of those forms of organ support.
This scoring approach combines two clinically important dimensions: survival and time without specified organ support. It is not simply a count of days free from organ failure among survivors, because death receives the lowest score. That feature makes interpretation dependent on the full distribution of scores, including how many patients die and how many remain free of support. The record describes the scale endpoints as -1 for death before day 28 and 28 for the highest score.
Using a median and interquartile range is a way to describe the center and spread of a distribution without assuming that its values are symmetrically distributed. The registry record specifies that summary format but does not report the observed median or interquartile range. It also does not report a confidence interval or other estimate of uncertainty for the primary outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that this was a small, single-group roll-in study of protocolized esmolol infusion, with enrollment of 7. It does not provide numerical results for organ-failure-free days or the named secondary outcomes. Consequently, the posted record cannot show the observed day-28 score distribution, its precision, or how participants' outcomes varied. A result should not be inferred from the study's completed status or from the protocol description.
There is no concurrent comparator in the registered design. Even if an outcome estimate were available, a single-group result would describe what occurred in this group under the study conditions; by itself, it would not establish what would have occurred without esmolol or under another treatment strategy. Differences in baseline illness, supportive care, and other factors cannot be separated from an intervention effect through a randomized, controlled contrast in this design.
The primary endpoint's scoring rule combines survival and days without specified organ support. That can capture more than one aspect of the clinical course, but it also means the distribution needs careful reading: death is assigned -1, and the highest possible score is 28. The record does not report how participants' scores were distributed, so it is not possible to tell whether any hypothetical central value would reflect a concentration of scores, a mixture of very different outcomes, or another pattern.
The record lists all-cause mortality, peak serum high-sensitivity troponin, left ventricular global longitudinal strain at 24 hours, and development of heart block as secondary outcomes. Their inclusion is not evidence that any particular value or event occurred. Numerical results for these outcomes are not reported in the registry record. The record also lists zero analyses, so no analysis results or inferential estimates are available there.
The safety record lists zero participants affected by serious adverse events and zero participants affected by other adverse events in the Esmolol group, with 7 at risk in each category; deaths are listed as 0. These figures describe the registry's recorded safety counts. They do not establish that the intervention has no safety risks, particularly given the limited enrollment and the absence of additional detail about event collection and follow-up in the registry record.
Overall, the record supports a description of the study's design, intended protocol role, and registered outcomes. It does not support a numerical conclusion about the primary endpoint, a comparative treatment effect, or the statistical uncertainty around an effect. The protocol-development purpose and the absence of a control group should guide any interpretation of the study's role.
9. Statistical Methods Explained
The registered design is single group, with allocation listed as NA and masking listed as none. In a single-group study, outcomes are described within the enrolled group rather than contrasted with outcomes from a concurrently assigned control group. That distinction is fundamental: within-group outcome summaries do not isolate the effect of an intervention from the course of illness, usual care, or other influences. The registry explicitly identifies this study as a roll-in intended to assess protocols for a future main study.
What does a median and interquartile range describe?
The primary outcome is specified as a median with an interquartile range. In general, the median is the middle of an ordered set of observations. The interquartile range describes the span containing the central half of those observations. These summaries can be useful when data are skewed or when a scale has limits or unusual values. They describe the observed distribution, not the precision of an estimated treatment effect. A confidence interval would address uncertainty in an estimate, but one is not reported for the primary outcome in the registry record.
The endpoint's scale runs from -1 for death on or before day 28 to 28 for a patient with 28 days without vasopressor therapy, mechanical ventilation, or renal replacement therapy. Because the score combines death and days without organ support, the median alone would not fully describe the pattern of outcomes. The spread and the score definition are relevant to interpretation. The registry record does not provide the observed median, interquartile range, or individual-level distribution.
Why is a control group important?
A concurrent control group provides a reference for what happened under a different assigned strategy during the same trial. Random assignment can help balance measured and unmeasured prognostic factors across groups, while masking can reduce some forms of bias in care or outcome assessment. Neither a randomized comparison nor masking is described for this study: allocation is NA, masking is none, and the model is single group. The result is not a direct estimate of a treatment contrast.
Without a comparator, observed changes or outcomes cannot be attributed to esmolol alone. Patients with septic shock may have changing illness severity and receive other care; the registry record does not supply details that would permit those influences to be disentangled. This is especially relevant for a roll-in study whose stated purpose was to evaluate protocol adequacy and efficiency before a separate main study.
What do the sample-size assumptions mean?
The registry's planning framework describes a sample-size illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes detecting stated fractions of the observed effect. Such calculations are planning illustrations, not observed power, and they are not evidence that the current single-group roll-in was designed as a two-arm comparison. The record does not report the study's own sample-size justification. Any estimate based on an observed effect should not be read as a guarantee that a future study will reproduce that effect.
In general, a planning calculation depends on assumptions about the effect to detect, variability, allocation, and the analysis. Departures from those assumptions can change the required sample size. The registry record does not report the detailed inputs or a protocol-based justification for enrollment of 7. Because this study is single group, a two-arm planning framework should be kept distinct from its registered design.
What can be concluded from the analysis record?
The registry lists zero analyses and does not report numerical results for the primary or secondary outcomes. Thus, it supplies no inferential analysis to evaluate, such as an adjusted estimate, a test statistic, or a p-value. Those details are not reported in the registry record. It would be inappropriate to infer a statistical result from the registered outcome definitions, the completed status, or the safety counts.
For general statistical interpretation, estimates and uncertainty intervals help distinguish a plausible range of effects from a single point estimate. In a controlled trial, an interval for a between-group contrast can indicate both the direction and precision of that contrast. Here, there is no reported contrast or uncertainty interval, and no comparator group in the design. The statistical record therefore supports no estimate of comparative efficacy or precision.
The endpoint is a bounded score with a special value assigned to death. In general, such distributions may be non-normal or concentrated at particular values. A summary method should reflect the scale and distribution; the registry specifies a median and interquartile range, but does not report further modeling choices. The choice of a median is descriptive and does not, by itself, account for confounding or make a causal comparison possible.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures, including organ-failure-free days as the primary outcome and named secondary outcomes of all-cause mortality, peak serum high-sensitivity troponin, left ventricular global longitudinal strain at 24 hours, and development of heart block. It does not report a multiplicity strategy, such as how interpretation would account for examining more than one outcome. The handling of multiplicity is not reported in the registry record.
In general, testing multiple outcomes can increase the chance of observing a seemingly notable result by chance if each is interpreted independently. A prespecified hierarchy or adjustment can help address that issue. No such plan is described in the registry record, and there are no reported analysis results from which to assess how outcomes were handled.
Methods for missing data, including whether any primary-outcome observations were missing and how missingness would be addressed, are not reported in the registry record. The record also does not state which analysis population was intended, such as whether analyses would include all enrolled participants or only those meeting particular treatment or follow-up criteria. No assumptions about missingness or analysis populations should therefore be attributed to this study on the basis of the registry record.
These omissions limit reproducibility and make it difficult to assess whether the planned analyses were followed. The record does not provide enough information to determine how incomplete follow-up, deviations from the infusion protocol, or the set of participants included in an analysis might affect the results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Esmolol | 0 | 7 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Esmolol | 0 of 7 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Esmolol | 0 of 7 |
For the Esmolol group, the registry lists 7 at risk for serious adverse events and 0 affected. It also lists 7 at risk for other adverse events and 0 affected. Deaths are listed as 0. No serious adverse-event terms are listed in the record.
These counts are descriptive registry entries, not proof that adverse events cannot occur. With enrollment of 7, a count of zero affected participants has limited ability to characterize uncommon or delayed harms. The record does not report further details about the adverse-event collection period, event definitions, severity grading, or how events were assessed; those details are not reported in the registry record.
At-risk counts and affected counts should be read separately: the former identify the group included in each safety category, while the latter record how many were reported as affected. The registry's zero counts do not establish a comparison with another treatment, since no control group is registered. They also do not support a broad safety conclusion beyond the recorded observations in this study.
12. What the Result Does, and Does Not, Mean
This study's registry record describes a prospective, phase 2, single-group roll-in of esmolol infusion in patients with septic shock and persistent tachycardia after adequate intravenous volume expansion. Its stated role was to assess the adequacy and efficiency of protocols for an anticipated main study. Enrollment was 7, and the study is recorded as completed.
The record does not report numerical results for organ-failure-free days or for the named secondary outcomes. It therefore does not establish the observed primary-outcome distribution, the precision of an outcome estimate, or a comparative effect. The single-group design also means there is no concurrent control result against which to compare outcomes. A conclusion that esmolol caused a particular outcome would go beyond the registered design and the results available in the record.
The primary score has a meaningful but composite interpretation: it assigns -1 to death on or before day 28 and 28 to reaching day 28 without vasopressor therapy, mechanical ventilation, or renal replacement therapy. If numerical results were available, interpretation would need to consider both survival and freedom from those forms of organ support, as well as the score's distribution. The registry record does not provide those data.
The safety entries record zero participants affected by serious adverse events, zero affected by other adverse events, and zero deaths, among the listed Esmolol safety group. These observations should not be taken as evidence of absence of risk or as a comparative safety finding. The limited enrollment and lack of a control group constrain what the safety counts can establish.
The appropriate interpretation is therefore narrow: the registry documents a completed protocol roll-in and its planned outcomes, but it does not provide the results needed to assess the primary endpoint or estimate treatment effects. The study's stated protocol-development purpose is distinct from confirming a clinical benefit or harm.
13. Why This Trial Matters Statistically
This trial matters statistically because its purpose and design shape what its data can answer. A roll-in study can provide experience with study procedures before a larger, separate study, and the registry explicitly describes protocol adequacy and efficiency as its objective. That is different from estimating a comparative treatment effect. Reading the study as though it were a randomized efficacy trial would misrepresent its structure.
The single-group design makes descriptive summaries central. It can characterize what was recorded in the enrolled group, but it cannot provide a concurrent counterfactual for what would have happened under another strategy. Allocation is listed as NA, masking as none, and no control arm is registered. These features should remain visible when considering any interpretation of outcomes.
The primary endpoint also illustrates an important measurement choice. Organ-failure-free days is not just a count of days without organ support: the registered score assigns a value of -1 for death on or before day 28 and a value of 28 for the highest score. A measure that integrates survival and days without support can represent several dimensions of a clinical course, but readers need the score definition and distribution to understand what a summary means. The registry record specifies a median and interquartile range but does not report those values.
Finally, statistical conclusions depend on outcome data and analysis details, not only on a registered design. The record lists eight outcome measures and zero analyses, and numerical outcome results are not reported. This leaves no basis in the registry record for estimating the primary result's precision, assessing multiplicity handling, or comparing outcomes between groups. The case underscores why protocol-development studies, outcome definitions, and complete reporting of results each have distinct roles in clinical research.
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 for interpretation is the absence of numerical outcome results in the registry record. Although the primary endpoint and secondary outcomes are identified, the record does not report the primary median or interquartile range, numerical secondary outcomes, or inferential analyses. The study's completed status does not fill this gap.
Enrollment was 7, and the study had a single group. This limits the descriptive information available and leaves no randomized concurrent comparator for estimating a treatment contrast. The registered design does not support separating an intervention effect from the natural course of illness, other care, or differences among patients.
The stated objective was to evaluate protocols for an anticipated main ECASSS study. As a roll-in, the study's purpose differs from a definitive comparative evaluation. The record does not report its protocol, eligibility criteria, adherence to the infusion procedure, handling of protocol deviations, or study-specific sample-size justification. These omissions limit assessment of implementation and reproducibility.
Several analysis details are also not reported in the registry record: the statistical plan, missing-data methods, analysis population, multiplicity approach, and uncertainty estimates. The safety record lists zero affected participants in its adverse-event categories, but event-collection details are not reported. These limitations mean that the available registry information is insufficient for a complete assessment of outcome reliability, safety follow-up, or treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Esmolol Infusion for Patients With Septic Shock and Persistent Tachycardia — NCT02841241.
- Registry record last updated 2019-01-09; status last verified 2018-12.
- Results first posted 2019-01-09.
- 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.
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18. Record Summary
NCT02841241 is a completed phase 2, prospective, single-group roll-in study sponsored by Intermountain Health Care, Inc. The registry records a start of 2016-04, primary completion of 2017-03, and enrollment of 7. The study examined protocolized esmolol infusion for patients with septic shock and persistent tachycardia after adequate intravenous volume expansion, with the stated aim of assessing protocols for an anticipated main ECASSS study.
The primary endpoint was organ-failure-free days at day 28, summarized by median and interquartile range. The registry also names secondary outcomes concerning mortality, high-sensitivity troponin, cardiac strain at 24 hours, and heart block. It lists eight outcome measures and zero analyses, but numerical outcome results are not reported in the registry record. The design has no concurrent control group, and the registered safety counts list zero participants affected by serious or other adverse events and zero deaths.