Human Amniotic Membrane to Decrease Post Operative Atrial Fibrillation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Human Amniotic Membrane to Decrease Post Operative Atrial Fibrillation (NCT04130061), a randomized early/phase 1 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

The study asks whether applying human amniotic membrane (hAM) during coronary artery bypass grafting can be evaluated for safety and feasibility in relation to postoperative atrial fibrillation. The registry summary describes an aim of reducing inflammation and the subsequent substrate associated with postoperative atrial fibrillation. The primary posted outcome, however, is the number of participants with adverse events over 1 month, rather than a posted count of atrial fibrillation events.

3. Trial Design

This was a randomized, parallel-group, open-label study listed as EARLY PHASE1. The registry record says participants would be randomized 1:1 to receive hAM application or standard of care. Masking is listed as none, so the record does not describe blinding of participants or study personnel. The study status is COMPLETED.

The record gives enrollment as 27. For the posted primary outcome, the group labelled Randomized has 12 participants and the group labelled Control has 14. These outcome-group counts do not account for the enrollment figure on their own; how participant accounting relates to the posted outcome groups is not reported in the registry record. The Randomized and Control arm descriptions are blank, so the posted arm labels do not provide additional detail about treatment assignment.

The study start date is 2019-10-11, and the primary completion date is 2021-06-01. The sponsor is the University of Utah. The official title identifies the study as an evaluation of safety and feasibility of human amniotic membrane to decrease postoperative atrial fibrillation after coronary artery bypass grafting. The listed intervention is Human Amniotic Membrane, classified as biological.

The record does not report the detailed randomization sequence, allocation concealment, eligibility criteria, participant flow, or baseline characteristics. It also does not report a statistical analysis plan beyond the description attached to the adverse-event outcome. The designation early phase and the safety focus describe the trial’s registry classification and primary outcome; they do not, by themselves, establish the extent of evidence about efficacy or feasibility.

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.

Before assignment: One participant was enrolled and randomized to receive the intervention, but they ultimately did not have the membrane placed due to a miscommunication in the OR. This is the reason that 27 participants were enrolled but the total number for analysis was 26.

Overall Study

Reasons for not completing this period:

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 Number of Participants With Adverse Events, measured over 1 month.

The primary endpoint is the number of participants with adverse events during 1 month. It is a participant count: each group’s result records how many participants experienced an event, rather than the total number of separate event episodes. The posted results report 0 participants with adverse events in the Randomized group and 0 in the Control group.

The registry description identifies the safety issues to be assessed after epicardial application of amniotic membrane: a change in membrane color as a sign of hyperacute rejection, cardiac tamponade or constriction assessed by echocardiogram, and transmission of infectious diseases. The record does not give separate numerical results for these event types. It also does not provide a detailed operational definition of every adverse event included in the participant count.

A safety endpoint is relevant in a study introducing a biological material during cardiac surgery because it focuses on observed complications over the stated follow-up period. The registry description says adverse-event incidence would be reported as percentages with two-sided 95% confidence intervals, and that comparisons would use a chi-square or Fisher’s exact test as appropriate. General statistical context: counts and incidence estimates describe what was observed in the study groups, while intervals convey uncertainty about the underlying event rates. The primary outcome is not itself a direct measure of postoperative atrial fibrillation; a numerical atrial fibrillation outcome is not reported among the posted results.

7. Results Posted in the Registry

• Randomized: 0.0% (0/12) versus 0.0% (0/14) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry description gives a limited outline of the intended statistical approach for the primary adverse-event endpoint. It says adverse-event incidence would be reported as percentages with two-sided 95% confidence intervals. It also says comparisons between the amniotic-membrane treatment and control groups would use a chi-square test or Fisher’s exact test, depending on minimum expected cell frequencies. The record does not report which test was applied, and it contains no posted analysis record.

What does a participant count represent?

General statistical context: a binary outcome records whether each participant did or did not experience the event of interest. A participant count states how many people in a group had at least one such event. It differs from a count of event episodes, because one participant could experience more than one event while still being counted once for a participant-based endpoint. The primary endpoint is explicitly a count of participants with adverse events. The registry record does not say how recurrent events were handled beyond that participant-based measure.

For this endpoint, the posted counts are 0 in the Randomized group and 0 in the Control group. Group sizes are 12 and 14, respectively. General statistical context: an incidence percentage expresses the event count relative to the group size. The registry description says such percentages and two-sided 95% confidence intervals were intended, but numerical arm-specific incidence percentages and confidence intervals are not reported in the registry record.

Why might a chi-square or Fisher’s exact test be used?

General statistical context: a chi-square test evaluates whether the distribution of a categorical outcome differs between groups using an approximation that works best when expected cell counts are sufficiently large. With sparse data, an approximation may be unreliable. Fisher’s exact test instead calculates probabilities under the null hypothesis using the observed margins, and is commonly considered when expected cell frequencies are small. The registry description explicitly makes the choice depend on minimum expected cell frequencies. It does not state which method was used, provide a test statistic, or report a p-value.

With no events recorded in either group, the posted data are especially sparse for a comparison of event risk. General statistical context: absence of observed events does not demonstrate absence of risk, and a test of group differences cannot by itself establish equivalence. Equivalence requires a prespecified margin and an analysis designed to assess whether uncertainty lies within that margin; such a margin or analysis is not reported in the registry record. The posted risk difference is 0.0, with an interval from 0.0 to 0.0, but the interval method is not specified. The interval should therefore be interpreted as the posted estimate, not as a complete account of uncertainty about rare events.

What does the randomization contribute?

General statistical context: random allocation is intended to make treatment assignment independent of participant characteristics on average, which can support a fair comparison between groups. The registry describes randomized allocation with a 1:1 ratio and a parallel design. The record does not describe the sequence generation method, concealment of assignment, or any adjustments in analysis. Masking is listed as none. These omissions do not establish that a particular procedure was or was not used; the details are simply not reported in the registry record.

The record’s sample-size assumptions describe a planning illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such illustrations are planning scenarios, not observed power and not evidence that the trial was designed to detect a particular clinical effect. The trial’s own sample-size justification is not reported in the registry record. No numerical planning targets are included in the record.

What analysis details remain unclear?

The record lists 38 outcome measures overall, but no secondary results are posted. The primary endpoint description does not specify a statistical analysis population, the handling of missing outcome observations, or whether any covariates were considered. There is no report of interim analyses or multiplicity procedures. These details are not reported in the registry record. General statistical context: with multiple outcomes or repeated testing, multiplicity procedures may be used to manage the chance of false-positive findings; without a documented plan, readers cannot establish how such issues were addressed. For this result, the absence of a posted inferential analysis means interpretation should remain descriptive and focused on the event counts and posted risk difference.

10. Confidence Intervals and Precision

The posted primary outcome contains 0 adverse-event participants in each group, with 12 participants in the Randomized group and 14 in Control. Its risk-difference estimate is 0.0, and the posted interval runs from 0.0 to 0.0. The registry record does not state the confidence level or calculation method for this comparison interval. The primary outcome description does state that adverse-event percentages were to be reported with two-sided 95% confidence intervals, but numerical group-specific intervals are not reported in the registry record.

General statistical context: a confidence interval is a range of values generated by a method intended to reflect uncertainty in an estimate. Its width depends on the data and the method; a narrow interval is not automatically informative if the method or assumptions are unclear. In particular, observing no events in small groups does not imply that the underlying event rate has been measured with certainty. Methods designed for sparse binary outcomes can yield uncertainty bounds that remain above zero even when the observed count is zero.

The interval attached to the risk difference should therefore be read in context rather than as proof of identical risks. The record does not report how that interval was calculated, and it does not provide a p-value. The small outcome groups, unreported participant accounting, and absence of group-specific uncertainty intervals limit the precision that can be assessed from the posted information. The record also limits the primary safety observation to 1 month, so it cannot describe the precision of longer-term risks.

Planning illustrations based on an observed effect are not a substitute for an uncertainty interval around the event rates and should not be interpreted as observed power. In this study, the planning assumptions are described, but the trial’s own sample-size justification is not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 38 outcome measures overall, while no secondary outcome results are posted. It identifies adverse events as the primary outcome and describes a planned comparison between the amniotic-membrane and control groups. A multiplicity strategy for handling several outcomes or analyses is not reported in the registry record. It is not possible to determine from the posted information whether other outcomes were analyzed but not reported, or whether the listed outcomes were all intended for inferential testing.

Missing outcome information is also not described. The primary result groups include 12 participants in the Randomized group and 14 in Control, while enrollment is listed as 27. The registry record does not explain the relationship between enrollment and these endpoint-specific group counts, identify any participants without outcome data, or state how missing values were handled. The analysis population is not reported in the registry record, so it is unclear whether the result represents all randomized participants, participants with available outcome data, or another population.

General statistical context: missing data can affect an estimate when the probability of being observed is related to participant characteristics or outcomes. The extent and direction of any effect depend on why data are missing and how the analysis handles them. Multiplicity can also affect interpretation when many outcomes or comparisons are considered, because repeated testing can increase the chance of at least one apparently unusual result. Neither issue can be resolved from the posted counts alone.

The registry describes chi-square or Fisher’s exact testing for the adverse-event comparison, but it does not report which test was used, a p-value, or any analysis record. Interim analyses, adjustments for multiple testing, and prespecified analysis populations are not reported in the registry record. These omissions mean the available information supports a focused descriptive reading of the primary counts, not reconstruction of the complete analysis plan.

12. 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 serious adverse-event information reports 0 serious events among 12 participants at risk in the Randomized group and 0 among 14 participants at risk in Control. Other adverse events are also reported as 0 in both groups, and deaths are reported as 0 in both groups. No leading serious-event terms are listed.

These figures describe what was recorded for the posted safety categories; they do not prove that the true risk of serious events is zero. General statistical context: rare events may not appear in a small study even when a risk exists, and an absence of events in a limited follow-up period gives only limited information about event frequency. The primary outcome timeframe is 1 month. The record does not give additional follow-up duration for the serious-event figures or separate event-level descriptions.

The registry’s adverse-event description names membrane color change, cardiac tamponade or constriction assessed by echocardiogram, and transmission of infectious diseases. The posted results do not provide separate counts for these concerns. The record also does not explain participant accounting between the enrollment figure and the safety groups. Accordingly, the safety figures are best read as zero recorded events in the stated groups, not as a guarantee of safety or a complete characterization of longer-term risks.

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

The posted result establishes a narrow descriptive finding: no participants were recorded as having an adverse event in either outcome group during the stated 1-month timeframe. The group labelled Randomized included 12 participants and Control included 14. The posted risk difference is 0.0, with an interval from 0.0 to 0.0. These figures do not establish that the underlying event risk is zero or that the groups have identical risks.

The study’s registry summary describes a goal of evaluating hAM application during cardiac surgery in relation to inflammation and postoperative atrial fibrillation. The primary posted outcome is adverse events, rather than a numerical comparison of postoperative atrial fibrillation. Atrial fibrillation results are not reported in the registry record. Therefore, the posted primary safety result does not answer whether the intervention changes the incidence of postoperative atrial fibrillation.

The study is listed as early phase, randomized, parallel, and open-label. Its enrollment is reported as 27, but the primary outcome groups account for 12 and 14 participants, and that relationship is not explained. Further details about eligibility, baseline characteristics, missing data, analysis populations, and the statistical method actually used are not reported. These gaps make it difficult to assess how representative the outcome groups are or how uncertainty should be quantified.

General statistical context: a small study can identify common or immediate problems, but is usually limited in its ability to characterize uncommon events. Zero observed events are therefore not equivalent to evidence that no risk exists. The result also cannot be extended beyond the recorded timeframe without longer-term data. The registry record does not report a prespecified equivalence margin, a trial-specific sample-size justification, or a posted inferential test result.

The appropriate interpretation is that the registry records no adverse events in the reported groups over 1 month, while leaving substantial questions about precision, participant accounting, and the atrial fibrillation objective unresolved. The result should not be treated as proof of efficacy, absence of risk, or a definitive comparison between treatment strategies.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary safety outcome has no recorded events in either group, while the outcome groups are small. Such data make clear why an observed count and an estimate of underlying risk are different things. Zero events are a valid description of what was recorded, but they do not alone establish that the risk is absent or precisely known.

The registry includes a planned approach that recognizes sparse-event concerns: it proposes chi-square or Fisher’s exact testing depending on minimum expected cell frequencies. This distinction matters because general large-sample approximations may not work well when expected counts are small. However, the record does not say which test was used or post a p-value. It also reports a risk-difference interval from 0.0 to 0.0 without identifying the calculation method. That combination illustrates why transparent reporting of methods is important when event counts are very low.

The study also separates its broader scientific aim from its primary endpoint. The stated aim concerns postoperative atrial fibrillation, but the primary posted result concerns adverse events. Keeping the endpoint distinction clear prevents safety counts from being mistaken for evidence about an atrial fibrillation outcome that is not numerically reported.

Finally, the reported enrollment and endpoint group counts are not reconciled in the registry record. Missing-data handling and analysis populations are also not reported. These are central details for interpreting who contributed to an estimate and how representative that estimate may be. The trial’s statistical value therefore lies not only in the observed zero counts, but also in showing how sparse outcomes, incomplete analysis reporting, and endpoint distinctions shape the limits of conclusions from early-phase clinical research.

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 primary limitation is the small number of participants represented in the posted outcome groups: 12 in the Randomized group and 14 in Control. With no events recorded, the data provide limited information about the frequency of uncommon adverse events. The 1-month primary timeframe also restricts the safety observation to that period; longer-term event results are not reported in the registry record.

Participant accounting is unclear. Enrollment is listed as 27, but the record does not explain how this figure relates to the two primary outcome groups. It does not report whether any participants lacked outcome data, how missing information was handled, or which analysis population was used. Baseline characteristics and detailed eligibility criteria are also not reported, limiting assessment of the study groups and the population to which the results might apply.

The registry describes a possible chi-square or Fisher’s exact comparison but does not identify the method actually used or report a p-value. It posts a risk difference of 0.0 with an interval from 0.0 to 0.0, without specifying the interval method. Numerical group-specific confidence intervals for adverse-event incidence are not reported. The trial’s own sample-size justification, interim analyses, and multiplicity procedures are not reported in the registry record.

The endpoint also differs from the study’s stated objective concerning postoperative atrial fibrillation. The primary posted result measures adverse events, and no numerical atrial fibrillation result is reported. Separate event counts for the safety concerns named in the endpoint description are not posted. These limitations mean the result is a limited descriptive safety observation, not a comprehensive evaluation of all stated objectives or a precise account of rare and longer-term risks.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Human Amniotic Membrane to Decrease Post Operative Atrial Fibrillation — NCT04130061.
• Registry record last updated 2026-04-09; status last verified 2024-12.
• Results first posted 2024-12-06.
• 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 identifies NCT04130061 as a completed, randomized, parallel, open-label, early-phase study sponsored by the University of Utah. Its title concerns human amniotic membrane to decrease postoperative atrial fibrillation after coronary artery bypass grafting. The study start date is 2019-10-11, the primary completion date is 2021-06-01, and enrollment is listed as 27.

The registry summary describes 1:1 allocation to hAM application or standard of care. The primary endpoint is the number of participants with adverse events over 1 month. The posted outcome groups report 0 participants with adverse events in the Randomized group and 0 in Control; their group sizes are 12 and 14. The posted risk difference is 0.0, with an interval from 0.0 to 0.0. A p-value and numerical atrial fibrillation outcome are not reported in the registry record.

The record lists 38 outcome measures overall but posts no secondary results. It does not explain the relation between enrollment and endpoint group counts, or report missing-data handling, the analysis population, or which statistical test was used.