Use of Amiodarone in Atrial Fibrillation Associated With Severe Sepsis or Septic Shock: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of Amiodarone in Atrial Fibrillation Associated With Severe Sepsis or Septic Shock (NCT02668432), a randomized phase 4 study. The primary outcome is Mean HR Every 6 Hours Within the First 7 Days.

2. Clinical Question

3. Trial Design

This was a phase 4, randomized, open-label, parallel-group clinical trial comparing full and partial amiodarone loading strategies. Randomization means that assignment was intended to occur by chance, but the registry record does not report the sequence-generation method, allocation concealment, or the procedure used to implement assignment. Open-label means masking was not used; the record does not describe whether any particular outcome assessment was conducted without knowledge of assignment.

The intended setting was a medical or cardiac intensive care unit at University Hospital. The study description identifies adults with new-onset atrial fibrillation during severe sepsis or septic shock, when the treating medical team considered amiodarone appropriate. The registry lists an enrollment of 9. It does not report how many participants were assigned to each strategy in the posted outcome analyses, nor does it provide participant flow, exclusions after randomization, or reasons for withdrawal.

The study began in 2016-05, had a primary completion date of 2018-09-20, and is listed as terminated. The registry does not state why the study was terminated or whether termination affected recruitment, follow-up, or analysis. It also does not report the planned enrollment target or a sample-size justification. Those details cannot be inferred from the enrollment figure alone.

The primary endpoint was mean heart rate measured every 6 hours within the first 7 days after initiation of amiodarone. The record also lists outcomes involving hemodynamic instability, rhythm conversion, time in atrial fibrillation, blood pressure, heart rate, and vasopressor use. The primary endpoint is described as a least-squares mean with standard error, but the model used to produce that measure is not reported in the registry record. No primary outcome estimates or statistical comparisons are posted.

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 Mean HR Every 6 Hours Within the First 7 Days, measured over 7 days.

The primary endpoint concerns mean heart rate, measured every 6 hours within the first 7 days following initiation of amiodarone. The registry gives beats per minute as the unit and describes the summary as a least-squares mean with standard error. The study description frames this repeated measurement as a way to compare heart-rate patterns under a full versus partial loading strategy. The brief summary states that assessment was to continue to day 7 or death.

Heart rate is a continuous measure, so a mean can describe the average level across observations or participants, depending on the analysis. The registry does not specify the precise averaging procedure, the statistical model, or how repeated measurements from the same participant were handled. A least-squares mean is generally a model-based mean; without the model specification, it is not possible to determine what adjustments or assumptions shaped the registry’s intended estimate.

The standard error describes the precision of an estimated mean, not the spread of individual heart-rate readings. The registry record does not report the least-squares means, standard errors, confidence intervals, or a comparison between groups. As a result, the endpoint definition can be described, but the posted record does not permit an assessment of the observed heart-rate pattern or the precision of any group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, open-label, parallel-group design and identifies a continuous primary endpoint. The following statistical concepts explain how such a comparison is commonly approached in general; they should not be read as a description of methods confirmed for this trial. The analysis plan and model details are not reported in the registry record.

What does randomization contribute?

In general, random assignment is intended to make the treatment groups comparable with respect to measured and unmeasured characteristics, on average. It does not guarantee that small groups will be balanced on every characteristic. Allocation concealment is a separate feature that concerns whether upcoming assignments could be anticipated before enrollment; that procedure is not reported in the registry record. The record identifies the study as randomized but does not describe the randomization sequence or its implementation.

What does a least-squares mean represent?

In general, a least-squares mean is an estimate derived from a statistical model. It can represent an adjusted group mean under the model’s assumptions and covariate structure. The estimate may differ from a simple arithmetic average if the model includes adjustments or handles the data structure in a particular way. The registry identifies the primary summary as a least-squares mean but does not identify the model, covariates, link or covariance structure, or estimation procedure. It is therefore not possible to tell which adjustments, if any, were used.

The standard error accompanying a mean describes the estimated precision of that mean. It is distinct from the standard deviation, which describes variation among observations. A confidence interval uses an estimate and its uncertainty to express a range of values compatible with the data under specified assumptions. No standard errors or confidence intervals for the primary endpoint are reported in the registry record.

Why does repeated measurement matter?

Heart rate was intended to be assessed every 6 hours within the first 7 days. Measurements from the same participant are generally correlated: a participant’s reading at one time can be related to that participant’s readings at other times. General analyses of repeated measurements account for this dependence rather than treating every reading as independent. Treating correlated readings as independent can understate uncertainty and distort statistical tests. The registry does not report how repeated observations were modeled or whether a single overall contrast, time-specific contrasts, or a trajectory summary was planned.

In general, repeated-measures methods also need to specify what happens when observations are missing. Some models can use incomplete measurement sequences under stated assumptions, but those assumptions matter, especially when missingness may be related to the participant’s condition or outcome. The registry record does not state how missing heart-rate assessments were handled, whether measurements after treatment changes were included, or how death affected the analysis. Because the study summary says follow-up continued to day 7 or death, death may limit the period in which measurements exist; the analytic treatment of that situation is not reported.

How should an arm comparison be read?

In general, a comparison of group means needs an estimate of the difference and an uncertainty measure. The estimate describes the observed contrast under the chosen analysis; the uncertainty indicates how much the estimate may vary across comparable studies under the model. A p-value, if reported, addresses compatibility with a specified null hypothesis and model assumptions; it does not quantify clinical importance or prove that a hypothesis is true. No contrast estimate, confidence interval, or p-value is posted for this primary endpoint.

Statistical significance and practical importance are separate questions. A precise estimate can still represent a small difference, while an imprecise estimate can leave a range of materially different possibilities. Without an estimate and its uncertainty, neither question can be addressed for this trial’s primary endpoint. The registry record also does not provide a threshold for a clinically meaningful heart-rate difference.

What does the registry say about the analysis?

The record identifies the outcome as a continuous measure and names a least-squares mean and standard error. It does not provide a statistical analysis plan, named analysis population, adjustment strategy, handling of multiple outcomes, or primary outcome results. The study description mentions JMP 12.0 and SPSS for analysis, but software names do not establish which procedures were used or which model assumptions were applied. No calculation or inference beyond the registry’s the registry entries can fill those gaps.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary heart-rate endpoint and additional outcomes involving hemodynamic instability, sinus-rhythm conversion, time in atrial fibrillation, mean arterial pressure, systolic blood pressure, heart rate, and vasopressor use. Considering multiple outcomes or multiple time-specific comparisons can increase the chance of finding an apparently notable result by chance. In general, investigators may address this through a prespecified hierarchy, adjusted significance thresholds, or an explicitly exploratory interpretation. The registry record does not report whether any multiplicity strategy was planned or used.

The primary endpoint itself includes repeated measurements every 6 hours within the first 7 days. The record does not clarify whether the intended primary inference was about a single summary across time, separate time-specific means, or another contrast. It also does not report whether repeated time points were treated as a family of tests. Without that information, the intended inferential target cannot be reconstructed.

Missing data are also relevant because the study summary describes follow-up to day 7 or death. The registry does not state how missing readings, early discontinuation, death, or other incomplete observations were handled. It does not identify an intention-to-treat, per-protocol, or other analysis population, and it does not report participant flow or the number contributing to each endpoint.

The registry lists 16 outcome measures and no analyses. The absence of posted analyses means that there is no reported multiplicity adjustment, missing-data method, or analysis population to evaluate. Those details are not reported in the registry record; they should not be inferred from the endpoint description or the software named in the study summary.

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 adverse-event record lists 0 serious adverse events affected among 5 at risk in the Partial Load group and 0 among 4 at risk in the Full Load group. It also lists deaths of 4 in the Partial Load group and 1 in the Full Load group. These are the registry’s recorded counts; they should be read as descriptive figures, not as an estimate of comparative risk.

The record does not explain the causes or timing of the deaths, whether they were considered related to amiodarone, or how deaths were classified relative to serious adverse events. The event counts do not establish that a treatment strategy caused an outcome. The record also does not list serious adverse-event terms. A count of 0 recorded affected participants does not establish that no clinically important events occurred outside the registry’s reported categories or observation procedures.

The at-risk counts are those listed for the adverse-event record, and should not be assumed to be the number analyzed for the primary heart-rate endpoint. The registry does not provide event-level descriptions, follow-up completeness, or a statistical comparison of the safety counts. No conclusion about relative safety can be drawn from these figures alone.

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

The record establishes that investigators planned a randomized comparison of full and partial amiodarone loading strategies in adults with new-onset atrial fibrillation associated with severe sepsis or septic shock. It identifies mean heart rate measured every 6 hours within the first 7 days as the primary endpoint and lists several additional clinical outcomes. It also records enrollment of 9 and a terminated status.

What the record does not establish is the result of the primary comparison. No group-specific heart-rate estimates, between-group contrast, confidence interval, or p-value is reported. The information therefore cannot show whether the observed heart-rate measurements differed, how large any difference was, or how precisely it was estimated. A missing analysis should not be interpreted as evidence of no difference.

The safety counts are also limited. The registry records 0 serious adverse events affected in each group and deaths of 4 in Partial Load and 1 in Full Load, but does not explain causes, timing, attribution, or comparative analysis. Those figures do not demonstrate that a loading strategy caused or prevented an event.

More broadly, a randomized design can support a comparison when assignment, follow-up, outcome measurement, and analysis are adequately documented. Here, key analysis details—including the model, handling of repeated measurements and missing data, and analysis population—are not reported in the registry record. The trial’s termination reason and planned enrollment are also not reported. These gaps limit what can be learned from the posted information, independently of the clinical question’s importance.

The defensible interpretation is therefore descriptive: the registry records the study design, intended endpoint, enrollment, status, and selected adverse-event counts, but does not post results for the principal heart-rate comparison. No statement that either strategy is superior, equivalent, effective, or ineffective follows from this record.

13. Why This Trial Matters Statistically

This trial addresses a statistical challenge common to intensive-care research: measuring a continuous outcome repeatedly in a population whose clinical course may change quickly. Heart rate was intended to be assessed every 6 hours, with follow-up to day 7 or death. Such data can describe both average levels and changes over time, but the analysis needs to account for correlation among measurements from the same participant and for incomplete follow-up.

The randomized comparison is conceptually useful because it asks about two dosing strategies within a defined clinical setting. However, randomization alone does not provide a result. Interpretation also depends on transparent reporting of group allocation, outcome data, estimates, uncertainty, and analysis choices. The registry record does not report the primary estimates or analysis, so the planned statistical comparison cannot be evaluated from the posted information.

The trial also illustrates why enrollment and endpoint data should not be conflated. The record lists enrollment of 9, but does not report the number contributing measurements at each time point or the analysis population. Repeated-measures outcomes may have different amounts of information at different times, particularly when observation ends at death. Without participant flow and an explicit missing-data approach, the extent and pattern of available data remain unclear.

Finally, the registry lists several outcomes in addition to the primary endpoint. Multiple outcomes and time-specific assessments raise questions about which comparisons were prespecified and how interpretation was protected from selective emphasis. The record does not report a multiplicity strategy. These are not merely technical details: they determine what an estimate means and how confidently it can be interpreted. The study is statistically informative as an example of a clinically focused design whose posted record leaves its central outcome analysis unreported.

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 primary limitation of the posted record is the absence of outcome estimates and statistical comparisons. Although mean heart rate is identified as the primary endpoint, the registry does not report group means, a group contrast, standard errors, confidence intervals, or p-values. The record therefore cannot answer the trial’s primary comparative question.

The registry lists enrollment of 9 and a terminated status but does not explain why the study was terminated, whether recruitment ended as planned, or whether follow-up was completed. It does not report the planned enrollment, sample-size justification, participant flow, group-specific primary-outcome data, or the number of observations available at each assessment. These omissions prevent assessment of how much information was available for the intended analysis.

Methods needed to interpret the repeated heart-rate endpoint are not reported. These include the statistical model, handling of within-participant correlation, any covariate adjustment, the definition of the main contrast, missing-data procedures, and the analysis population. The role of death in the endpoint analysis is also unclear, although the summary describes follow-up to day 7 or death.

The intervention descriptions are incomplete. The brief summary gives a full-loading description beginning with at least 5g IV, while the arm descriptions include shared initial infusion details; the complete quantitative distinction between the strategies is not available in the registry record. The record also does not report treatment adherence, crossover, or changes in therapy.

Safety reporting is limited to the listed counts. Causes, timing, attribution, and event-level details are not reported. These limitations concern the registry information available for interpretation and should not be mistaken for findings about the underlying study data.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Use of Amiodarone in Atrial Fibrillation Associated With Severe Sepsis or Septic Shock — NCT02668432.
• Registry record last updated 2019-04-02; status last verified 2018-11.
• Results first posted 2019-04-02.
• 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

NCT02668432 is a phase 4, randomized, open-label, parallel-group trial of full versus partial amiodarone loading strategies for new-onset atrial fibrillation associated with severe sepsis or septic shock. The intended primary endpoint was mean heart rate every 6 hours within the first 7 days after amiodarone initiation, with the summary describing follow-up to day 7 or death. The registry lists enrollment of 9, a start date of 2016-05, a primary completion date of 2018-09-20, and a terminated status.

The registry record does not report the primary outcome estimates or analyses, the statistical model, the analysis population, missing-data methods, or the reason for termination. It records 0 serious adverse events affected in each arm and deaths of 4 in Partial Load and 1 in Full Load, without event attribution or comparative analysis. The posted record describes the intended comparison but does not establish its heart-rate result.