Repeated Amiodarone Dosing In Cardiac surgicaL Procedures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Repeated Amiodarone Dosing In Cardiac surgicaL Procedures (NCT05004077), a randomized phase 4 study. The primary outcome is Normal Sinus Rhythm -24 HRS.

2. Clinical Question

The question is a comparison of two treatment strategies in a specific postoperative setting, not a comparison of amiodarone with no treatment. The registered primary outcome is normal sinus rhythm at 24 hours after the amiodarone bolus. Its description frames the outcome as the percentage of patients who converted to normal sinus rhythm under the repeated-bolus regimen compared with the percentage under the conventional intravenous loading regimen.

The registry describes the trial as prospective, randomized, open-label, and single-center. The enrollment was three participants, and the record says outcome data were not released because one group had a single participant and disclosure could affect confidentiality. Accordingly, the registered question is clear, but the posted record does not provide the outcome values needed to estimate the comparison or its uncertainty.

3. Trial Design

This was a phase 4, randomized, open-label, parallel-group trial. The study summary describes it as prospective and single-center, at the University of Kentucky Chandler Medical Center. It enrolled patients who developed atrial fibrillation after non-emergent cardiac surgery. The two groups were assigned to conventional amiodarone dosing or repeated amiodarone bolus dosing.

The recorded enrollment was three participants. The adverse-event record shows two participants at risk in the conventional-dosing group and one in the repeated-bolus group. This is a very small enrollment for comparing outcomes between groups, and the unequal group counts leave very little information for estimating a treatment contrast. The registry reports that the primary outcome data were withheld because one group had only one participant and displaying its outcome could affect confidentiality.

The conventional regimen description specifies an initial 150 mg intravenous bolus over 10 minutes, then a 24-hour loading infusion of 1 mg/min for 6 hours followed by 0.5 mg/min for 18 hours, followed by enteral dosing. The repeated-bolus description also specifies an initial 150 mg intravenous bolus over 10 minutes, then infusions of 1.0 mg/min for 6 hours and 0.5 mg/min for 18 hours, followed by enteral dosing. The registry’s arm descriptions stop before all enteral regimen details are complete; additional details are not reported in the registry record.

The recorded start date was 2021-11-02, and the primary completion date was 2022-10-10. The study status is terminated. The reason for termination is not reported in the registry record. The sponsor is Kevin W Hatton, MD, PhD. The record lists four secondary outcomes: total target heart rate time, time to target heart rate, normal sinus rhythm at hospital index, and recurrent atrial fibrillation. It lists five outcome measures in total and zero analyses.

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: No data released because enrollment was three participants, and one group had a singular participant. Therefore, confidentiality of the participant's health information could be impacted if the outcome measures were displayed.for that group with only one participant. Additionally, the other group only had two participants, again, release of this information could impact their right to confidentiality.

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 Normal Sinus Rhythm -24 HRS, measured over 24-hours after receiving amiodarone bolus.

The primary endpoint is normal sinus rhythm at 24 hours after receiving the amiodarone bolus. Its registry description defines the comparison in terms of the percentage of patients who converted to normal sinus rhythm after the repeated amiodarone bolus and loading regimen versus the percentage who converted after the conventional intravenous loading regimen. The stated timeframe is 24 hours after receiving the amiodarone bolus.

This endpoint is intended to describe rhythm status at a specified time after dosing. In general, a binary endpoint such as being in normal sinus rhythm or not can be summarized as a proportion in each treatment group, then compared between groups. That comparison would depend on the outcome definition, the number of participants with an observed status, and the method chosen for estimating uncertainty. Those group-specific counts and estimates are not reported in the registry record.

The registry does not report a unit, statistical parameter, or dispersion measure for this outcome. It also does not provide the underlying categories or group-level values. The record states that outcome data were not released because enrollment was three participants and one group contained a single participant; displaying the outcome could risk participant confidentiality. As a result, the intended endpoint can be described, but the posted record cannot establish the observed proportion in either group or the size and precision of any difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is a way to assign participants to treatment groups using a chance-based process. In general, random allocation is intended to reduce systematic differences between groups at the time of assignment. It does not guarantee that groups will be similar in every characteristic, particularly when enrollment is very small. This trial is described as randomized and parallel-group, with participants assigned to one of two amiodarone dosing regimens. The registry does not report the randomization sequence method, allocation concealment, or procedures used to implement assignment.

What would a group comparison estimate?

For the primary endpoint, a direct descriptive summary would be the proportion in each group who were in normal sinus rhythm at 24 hours after the amiodarone bolus. A comparative analysis could then express how those proportions differ under a specified statistical measure. The choice of measure matters: a difference in proportions and a ratio of proportions answer related but distinct questions. The registry record does not report a statistical parameter or an analysis method for this outcome, and the outcome data themselves are not released.

In general, an estimate is a sample-based value used to describe a quantity of interest in a wider population. A confidence interval gives a range of values compatible with the observed data under a specified model and procedure. With sparse data, such an interval can be wide, and conventional methods may behave poorly when event counts are very low or a group has only one participant. No confidence interval is reported for this trial’s primary outcome, so there is no interval whose width or compatibility with possible effects can be assessed.

Why is precision important?

Precision describes how much uncertainty surrounds an estimate. A point estimate alone can give an incomplete picture because different samples could produce substantially different estimates. Larger amounts of information generally allow more precise estimates, while very small samples provide little ability to distinguish a real group difference from chance variation. Here, only three participants were enrolled, and the registry withheld primary outcome values for confidentiality. Thus neither the estimate nor its precision is available for interpretation.

A p-value, when reported, is a measure calculated under a statistical model that addresses how compatible the observed data are with a specified null hypothesis. It is not the probability that the null hypothesis is true, and it does not by itself convey the size or clinical importance of an effect. No p-value or inferential analysis is reported for the outcomes in this record. It would not be appropriate to infer statistical significance or lack of significance from the absence of released results.

What do the design assumptions mean?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. Such illustrations are hypothetical calculations about the sample size that might be needed under stated assumptions. They are not observed power and are not evidence that a study was adequately powered. The registry record does not report a sample-size justification from the trial’s own design. No numerical sample-size illustration values are included in the record used for this analysis, and the primary outcome data needed to assess an observed effect are not released.

Equal allocation is an assumption in those planning illustrations, not a description of the observed enrollment: the adverse-event denominators are two participants in the conventional group and one in the repeated-bolus group. Planning calculations also depend on assumptions about the effect to detect, the outcome distribution, and the analysis method. If those assumptions do not match the study or the target question, the resulting illustration may not apply. The registry does not report further details about how its planning calculations were constructed.

How can unequal follow-up or event rates matter?

For a binary endpoint such as normal sinus rhythm at the stated time, each participant’s outcome must be classified according to the endpoint definition. If outcome status is unavailable for some participants, the analysis needs a rule for how to handle that missing information. Different rules can affect the estimate and its uncertainty. The registry does not report the number of missing primary outcomes, the outcome status for individual participants, or a missing-data method.

For count outcomes or event rates, general statistical methods may need to account for over-dispersion. Over-dispersion means that the observed variability is greater than a chosen probability model would expect. Ignoring it can make uncertainty appear smaller than it is. The registry lists outcomes involving time and recurrence, but it does not report the statistical models used or enough outcome data to assess whether over-dispersion or another modeling issue was relevant.

For time-to-event outcomes, general methods often distinguish the time until an event from whether an event occurred, and may account for participants who leave follow-up before an event is observed. The listed outcomes include time to target heart rate, but the registry does not report an analysis method, event-time results, censoring information, or analysis population. Consequently, it is not possible to determine whether a time-to-event method was used or to assess its assumptions.

What cannot be inferred from the record?

The registry lists zero analyses. It does not report interim analyses, a statistical analysis plan, prespecified covariate adjustment, an intention-to-treat or per-protocol population, or methods for multiplicity. Those features should not be assumed. A randomized design describes how treatment assignment was intended to occur; it does not, by itself, specify the statistical analysis or establish that the groups are comparable in a sample this small. Since the primary outcome values are withheld, and the other outcome results are not reported, no recalculated estimates can be made from posted summary statistics.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, normal sinus rhythm at 24 hours after the amiodarone bolus, and four secondary outcomes: total target heart rate time, time to target heart rate, normal sinus rhythm at hospital index, and recurrent atrial fibrillation. It reports five outcome measures in total and zero analyses. The registry record does not report a multiplicity procedure, such as an adjustment to account for evaluating several outcomes, nor does it explain how primary and secondary findings would be interpreted together.

In general, testing multiple outcomes can increase the chance of at least one apparently notable result arising by chance. A prespecified hierarchy or statistical adjustment can address that issue, but neither approach is reported in the registry record. Because outcome data and analyses are not posted, there are no reported results to assess for multiplicity or selective emphasis.

The registry does not report how missing outcome data were handled, whether any participants lacked a measured endpoint, or which analysis populations were used. It also does not report an intention-to-treat, per-protocol, or other analysis definition. These are important distinctions: the assigned-treatment population and the participants with observed outcomes may not be identical, and analysis choices can affect estimates. The primary outcome results were withheld for confidentiality, but that reason does not establish how missing data were handled in any analysis.

The record does not report interim analyses, stopping rules, or a statistical analysis plan. The study is marked terminated, but the reason for termination and whether it related to the planned analysis are not reported in the registry record. Without these details and without posted results, the analysis process cannot be reconstructed.

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 two participants at risk in the conventional amiodarone dosing group and one in the repeated amiodarone bolus dosing group. It reports zero serious adverse events, zero other adverse events, and zero deaths in each group. No serious adverse-event terms are listed.

These are small group counts, not estimates of the frequency of adverse events in a broader population. A zero count in a group with only a few participants does not establish that an event cannot occur or that the treatment has no safety risks. It means only that the registry reports no events of the listed types among the participants recorded at risk.

The record does not provide additional detail about the adverse-event definitions, the period of observation, event ascertainment, or whether all participants completed the same duration of follow-up. It also does not provide individual-level data. The figures should therefore be read as limited descriptive counts. They do not support a reliable comparison of safety between dosing groups.

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

The registry record documents a randomized, open-label comparison of conventional and repeated-bolus amiodarone dosing for patients who developed atrial fibrillation after non-emergent cardiac surgery. Its primary question concerns normal sinus rhythm 24 hours after the amiodarone bolus. The record also lists four secondary outcomes related to heart rate, rhythm, and recurrence. This identifies the intended clinical and statistical questions, but it does not provide the results needed to answer them.

Three participants were enrolled. The primary outcome values were not released because the registry states that one group had a singular participant and disclosure could affect confidentiality. No group-specific conversion percentages, effect estimate, confidence interval, or p-value are reported. It is therefore not possible to determine from the posted results whether the groups differed, how large a difference might have been, or how uncertain an estimate would be.

The adverse-event record reports no serious events, other events, or deaths in either group. In a study with three participants, these counts provide very limited information about safety and should not be interpreted as evidence that adverse events are absent in general. The registry also does not report the reason for termination, the analysis methods, missing-data handling, or analysis populations.

These findings do not establish that either regimen is better, worse, equivalent, or safe for a broader population. They describe what is available in a small registry record with withheld primary outcome data and no posted analyses. The planned randomized comparison and the observed enrollment are informative about the study’s scope, but the outcome comparison remains unresolved in the posted record.

13. Why This Trial Matters Statistically

This trial illustrates a basic distinction between a research question and an answer to that question. A randomized design can specify a comparison, an endpoint, and treatment groups, but it cannot yield an interpretable treatment estimate when outcome results are not available. Here, the primary question is defined around normal sinus rhythm 24 hours after amiodarone dosing, yet the registry reports that the outcome data were withheld for confidentiality reasons.

The record also demonstrates why enrollment matters for statistical interpretation. With three participants overall and only one in one group, a group comparison would be highly sensitive to individual outcomes. Even if the primary outcome values were displayed, the small amount of information would constrain precision and generalizability. The confidentiality rationale means those values cannot be used in the posted record, so there is no effect estimate to qualify with an interval or other uncertainty measure.

Another statistical lesson is that an endpoint list is not a results report. The registry identifies a primary outcome and four secondary outcomes, but lists zero analyses. Without reported estimates and methods, readers cannot assess the magnitude of effects, uncertainty, multiplicity, missingness, or consistency across outcomes. A stated planning approach does not substitute for outcome data, and planning illustrations are not observed power or evidence of an effect.

Finally, the safety counts require the same attention to denominators and study size as efficacy outcomes. Zero recorded events among a few participants is a descriptive observation, not a precise estimate of risk. This record is useful as an example of how design information, enrollment, privacy protection, and incomplete reporting shape what statistical conclusions can responsibly be drawn.

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 principal limitation is that the primary outcome values were not released. The registry explains that enrollment was three participants and that one group had a singular participant, so displaying outcome measures could affect confidentiality. This prevents estimation of the group-specific percentages and any direct comparison for normal sinus rhythm at 24 hours.

Enrollment was three, with two participants listed at risk in the conventional group and one in the repeated-bolus group. Such a small study cannot provide stable estimates of treatment differences or adverse-event frequencies. The unequal group counts also mean that the groups contribute very different amounts of information. No results are posted for the four secondary outcomes, so they cannot provide an alternate basis for assessing the comparison.

The study is marked terminated, but the reason is not reported in the registry record. The record does not report a statistical analysis plan, group-comparison method, analysis populations, missing-data handling, interim analyses, or multiplicity procedures. The arm descriptions do not include all enteral regimen details, and the duration and completeness of outcome follow-up are not reported. These omissions make it difficult to determine the exact treatment contrast and how outcomes would have been analyzed.

The record describes a single-center study at the University of Kentucky Chandler Medical Center and does not provide a broader account of participant characteristics or eligibility criteria. With no released outcome data and no analyses, there is no basis for judging whether the results would generalize beyond the enrolled participants. The zero adverse-event counts are also limited by the very small denominators and the absence of further follow-up detail.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Repeated Amiodarone Dosing In Cardiac surgicaL Procedures — NCT05004077.
• Registry record last updated 2023-11-18; status last verified 2023-10.
• Results first posted 2023-11-18.
• 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

This phase 4 study was a prospective, randomized, open-label, parallel-group trial at the University of Kentucky Chandler Medical Center. It compared conventional amiodarone dosing with a repeated-bolus dosing regimen in patients who developed atrial fibrillation after non-emergent cardiac surgery. The primary outcome was normal sinus rhythm 24 hours after receiving the amiodarone bolus.

Enrollment was three. The record lists four secondary outcomes and five outcome measures in total, with zero analyses. Primary outcome data were not released because one group contained a single participant and disclosure could affect confidentiality. The study status is terminated; the reason is not reported. The adverse-event record reports zero serious adverse events, zero other adverse events, and zero deaths in both groups, with two participants at risk in the conventional group and one in the repeated-bolus group.

Without posted outcome data or analyses, the registry record does not support an estimate of the primary treatment comparison or its precision.