Left Atrial Imaging Prior to Cardioversion: Leveraging Computed Tomography to Rule Out Thrombus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Left Atrial Imaging Prior to Cardioversion: Leveraging Computed Tomography to Rule Out Thrombus (NCT04223505), a randomized na study. The primary outcome is Time to Imaging.

2. Clinical Question

The clinical rationale described in the registry is to evaluate CCT as an alternative to TEE before cardioversion, with the aim of expediting cardioversion and reducing hospital admissions for atrial fibrillation and atrial flutter. Those aims are the stated rationale, not separate conclusions established by the primary time-to-imaging result. The registry identifies time to cardioversion as a secondary outcome, allowing a related but distinct timing question to be examined.

3. Trial Design

This was a randomized, parallel-group trial with no masking. It compared two diagnostic strategies: contrast-enhanced ECG-gated cardiac CT and transesophageal echocardiography. The condition listed in the registry is atrial fibrillation. The registry lists the trial phase as not applicable and reports an enrollment of 102.

The study status is completed. The recorded start date is 2020-06-26, and the primary completion date is 2023-11-21. Ottawa Heart Institute Research Corporation is listed as the sponsor. These administrative details describe the registered study; they do not provide information about how participants were recruited or how the random assignment sequence was generated.

The trial's primary outcome was time to imaging, expressed in hours and defined as the time between admission and imaging. The stated timeframe extends from admission to imaging or spontaneous cardioversion, up to approximately 30 days. Time to cardioversion, measured in days from admission, is listed as a secondary outcome. The registry lists four outcome measures, but details for additional outcomes beyond the primary measure and the posted secondary outcome are not reported in the registry record.

Random allocation supports a comparative design, but the registry record does not describe allocation concealment, the method used to generate the sequence, or whether any stratification was used. Masking is listed as none; further details about which staff or participants knew the assigned imaging strategy are not reported in the registry record. The study's original sample-size rationale and its full analysis plan are also not reported in the registry record. These gaps limit assessment of design details beyond the randomized, parallel-group structure.

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 Time to Imaging, measured over From admission to imaging/spontaneous cardioversion, up to approximately 30 days..

The primary endpoint is time to imaging, measured in hours from admission to imaging. The registry states that the outcome was calculated as the time between admission and imaging, with a timeframe from admission to imaging or spontaneous cardioversion, up to approximately 30 days. The reported summary is a mean with a standard deviation for each group.

This endpoint addresses the operational timing question underlying the comparison: how long it takes for patients assigned to each diagnostic approach to reach imaging. In a pathway where imaging informs decisions about cardioversion, time to imaging can describe one step in the care process. It is not a direct measure of diagnostic accuracy, the presence or absence of thrombus, or the clinical outcome of cardioversion. Nor does a group mean reveal every participant's experience; individual times may vary around the average.

The registry separately lists time to cardioversion as a secondary endpoint. That measure is related to, but not interchangeable with, time to imaging: it captures the interval to cardioversion rather than the interval to imaging. The distinction matters because a difference in the timing of imaging need not translate into the same difference in the timing of cardioversion. The registry record does not report additional endpoint definitions beyond those described for these measures.

7. Results Posted in the Registry

• CCT Arm: mean 7.10 versus 28.10 on control; difference -21.00 (95% CI -31.25 to -10.75), standardized effect d = -0.81; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Time to Cardioversion

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • CCT Arm: mean 1.70 versus 4.60 on control; difference -2.90 (95% CI -6.02 to 0.22), standardized effect d = -0.37; z-test p = 0.068.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CCT Arm and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists time to cardioversion as a secondary outcome, measured in days from admission. Its group means are lower in the CCT arm than in the TEE arm, matching the direction of the primary time-to-imaging comparison. However, the secondary interval includes zero, and its unadjusted p-value is 0.068. The pattern is therefore directionally consistent with the primary timing result but less conclusive in the posted comparison.

Time to cardioversion and time to imaging are related process measures, but they are not the same endpoint. Imaging is one step in the pathway; cardioversion is a later outcome. The registry's stated timeframes extend up to approximately 30 days for both measures. A pattern across these two measures can be informative descriptively, but it does not establish that the difference in time to imaging caused a difference in time to cardioversion.

Secondary results generally carry less weight than a primary result because they may be less central to the trial's main question and may be among several comparisons. When multiple outcomes are examined, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity plan or analyses. This limits how strongly the secondary comparison can be treated as confirmatory. The registry also lists four outcome measures, while details for only one secondary outcome are posted in the information; other outcome details are not reported in the registry record.

The secondary finding should thus be considered alongside, but not used to replace or amplify, the primary endpoint. It adds a related description of timing while leaving uncertainty about the exact mean difference and about how that measure relates to the primary result. It does not provide evidence about diagnostic accuracy, and it does not establish an effect on outcomes beyond the timing measures reported.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Time to Cardioversion

9. Statistical Interpretation

10. Statistical Methods Explained

What does a group mean describe?

The primary outcome is continuous: it records time on a scale measured in hours. A mean is the arithmetic average of the recorded times in a group. It offers a compact description of the group's central level, but it does not describe all individual values. The standard deviation describes how spread out observations are around the mean. A larger standard deviation indicates greater variation among observed times, but does not show the shape of that variation.

Here, the mean and standard deviation are reported separately for the TEE and CCT arms. The mean difference compares the CCT mean with the TEE mean using the direction stated in the posted comparison. A negative value indicates a smaller mean in CCT for this comparison. This is a difference in group averages, not a percentage change or an estimate of an individual's expected wait.

How should the confidence interval be read?

A confidence interval expresses uncertainty around an estimated effect. In general, it gives a range of values compatible with the observed data and the method used to construct the interval. A narrower interval indicates greater precision than a wider interval, all else being equal. The interval does not guarantee that the true value lies within its endpoints, and it does not show the range of individual participant times.

For the primary comparison, the confidence interval runs from -31.25 to -10.75 hours. Both endpoints are below zero, so the interval excludes no mean difference. For the secondary comparison, the interval runs from -6.015 to 0.215 days and includes zero. These intervals express uncertainty about the between-group mean differences, not uncertainty about whether an individual will experience a particular timing outcome.

What does the p-value add?

In general, a p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions are correct. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The primary comparison has an unadjusted p-value of <0.001; the secondary comparison has an unadjusted p-value of 0.068. The p-values should be read alongside the estimated differences and confidence intervals, rather than as stand-alone conclusions.

“Unadjusted” indicates that the reported p-values have not been adjusted for multiple comparisons. The registry record reports no analyses, and it does not report a multiplicity procedure. Thus, the results do not establish that the probability of a false-positive finding across all outcomes was controlled at a particular level. The number of outcome measures listed in the record is not, by itself, a description of which comparisons were prespecified or how they were prioritized.

Why does variation matter?

When observations vary widely, a group mean may conceal a broad range of experiences. The primary outcome's standard deviations are 34.9 hours for TEE and 12.5 hours for CCT. The standard deviation in the TEE arm is large relative to its mean. This cautions against interpreting the group average as typical for every participant or assuming that timing follows a symmetric distribution.

As a general statistical point, strong skew or a long tail can make a mean sensitive to a small number of long observations. Over-dispersion means that observed variation is larger than a model assumes; if an analysis does not account for that extra variation, standard errors and intervals may be too optimistic. The registry record does not describe a distributional assessment or a method addressing skewness or over-dispersion. No conclusion about the actual distribution of participant times can be drawn from means and standard deviations alone.

What is and is not documented about the analysis?

The registry record lists no reported analyses. The posted group summaries and comparison estimates allow a descriptive reading of the primary and secondary outcomes, but they do not document the full statistical analysis plan. The analysis population, treatment of missing data, adjustment variables, and rules for handling protocol deviations are not reported in the registry record. It is also not reported in the registry record whether the comparison used an intention-to-treat, per-protocol, or other population.

Randomization is intended, in general, to support a fair comparison by assigning participants to groups without choosing the group based on measured or unmeasured characteristics. It does not ensure that the groups are identical, especially in a trial of this size, and it does not remove the need to describe who was analyzed. The record does not provide enough detail to evaluate the randomization implementation or the balance of baseline characteristics.

What do planning calculations mean?

The planning figures are illustrations based on fractions of the observed effect, not a reconstruction of the trial's original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For these continuous outcomes, the figures refer to participants per arm. In general, a power calculation estimates how often a specified analysis would detect a particular effect under its assumptions, if the effect were present.

Planning for a smaller effect requires more participants than planning for a larger effect, because a smaller difference is harder to distinguish from random variation. Such calculations depend on assumptions about the effect, variability, allocation, and analysis. The trial's original sample-size justification, original target, and original design assumptions are not reported in the registry record. These planning illustrations should therefore be interpreted only according to their stated assumptions, not as evidence about the trial's design decisions.

11. Confidence Intervals and Precision

The primary mean difference is -21.0 hours, and its 95% confidence interval extends from -31.25 to -10.75 hours. The interval is entirely below zero, which indicates that the posted estimate is more precise about the direction of the mean contrast than an interval spanning both negative and positive values would be. It nevertheless covers a range of possible mean differences, so the precise size of the contrast remains uncertain.

The endpoint's observed variability is relevant to precision. The TEE arm has a standard deviation of 34.9 hours, compared with 12.5 hours for CCT. Standard deviations describe variation among observations, whereas the confidence interval describes uncertainty in the estimated group contrast. They answer different questions: a group may have considerable individual variation while still having an estimated mean difference with a confidence interval that excludes zero.

For the secondary mean difference of -2.9 days, the 95% confidence interval ranges from -6.015 to 0.215 days. Its inclusion of zero means the data do not pin down the direction of the mean difference as clearly as the primary interval does. The interval also allows for a small positive difference under the posted analysis. The unadjusted p-value of 0.068 is consistent with this uncertainty; neither the p-value nor the interval determines clinical importance.

Confidence intervals do not address all sources of uncertainty. They depend on the analysis method and assumptions, and they do not account automatically for unreported missing-data procedures, selection of outcomes, or multiplicity. The registry record does not provide the analysis details needed to assess those issues. No interval for diagnostic accuracy or patient-level outcome is reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures for these continuous outcomes are expressed as participants per arm, not as a total across both arms and not as total events. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect: 100%, 75%, or 50%. These are planning assumptions for an illustration, not the trial's documented original design assumptions; the original design rationale is not reported in the registry record.

The 80% power column gives the number of participants per arm estimated to yield an 80% chance of detecting the specified effect under the listed assumptions. The 90% power column gives the corresponding estimate for a higher chance of detection, which requires more participants under the same assumptions. These are not guarantees: actual power depends on the true effect, variability, analysis method, and other conditions. The planning figures are not observed power.

For the primary endpoint, planning for 100% of the observed effect gives 25 participants per arm for 80% power and 33 participants per arm for 90% power. At 75% of the observed effect, the figures are 43 and 58 participants per arm; at 50%, they are 97 and 129 participants per arm. The general pattern is that smaller effects need more participants to detect. A sample-size curve should be read as illustrating that relationship across effect assumptions, not as a record of what the trial originally planned or achieved.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -21.000; pooled standard deviation σ = 26.010.
2. n = 2 × (1.96 + 0.842)² × 26.010² / -21.000² = 24.1, rounded up to 25 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -21                      # observed difference in means
sigma <- 26.0098519795865                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4223505)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 25 (80% power), 33 (90% power)
 75% of observed effect: n per arm = 43 (80% power), 58 (90% power)
 50% of observed effect: n per arm = 97 (80% power), 129 (90% power)
power.t.test: 25.1 
Simulated power at n = 25 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or analyses are tested. In general, as more tests are conducted, the probability of at least one result appearing notable by chance can rise. Prespecifying a primary endpoint and using an appropriate adjustment or hierarchy can help define how results should be interpreted. The registry identifies time to imaging as the primary outcome and lists time to cardioversion as a secondary outcome, but a multiplicity plan is not reported in the registry record. The posted p-values are unadjusted.

The registry record lists four outcome measures but provides details for the primary outcome and one secondary outcome. The remaining outcome definitions, results, and analysis choices are not reported in the registry record. It is also not reported in the registry record whether the secondary outcome was prespecified in the same way as the primary outcome, whether any outcomes were omitted from reporting, or whether additional comparisons were conducted. These uncertainties mean that the posted secondary p-value should not be read as if it came from a single, isolated test.

Missing-data methods and analysis populations are also not reported in the registry record. It is not stated how incomplete timing records were handled, whether participants who did not undergo imaging were included, or whether all randomized participants were analyzed in their assigned groups. The registry does not describe exclusions, protocol deviations, or sensitivity analyses. Those details are important because the estimated mean and its uncertainty can depend on which observations contribute to the analysis and how missing outcomes are treated.

The registry record reports no analyses. Accordingly, the available summaries do not establish the full analysis plan or show whether assumptions were checked. No adjustment for baseline characteristics is described, and no subgroup analyses are reported. These absences do not change the arithmetic of the posted summaries, but they limit independent assessment of analysis choices, robustness, and the scope of inference.

15. 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.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in the TEE arm among 50 at risk and zero in the CCT arm among 52 at risk. It also reports other adverse events in 14 participants in the TEE arm and 17 participants in the CCT arm, with the at-risk groups listed as 50 and 52, respectively. Deaths are listed as 1 in each arm.

These figures are counts as recorded in the registry and should be read separately by event category. The record does not report serious adverse-event terms, since no serious terms are listed. It does not state whether the deaths were considered serious adverse events, whether events were judged related to an imaging procedure, or the timing, severity, and definitions used for the other adverse events. The at-risk counts do not establish how the registry handled missing safety information.

Small event counts and limited detail make it difficult to compare safety patterns or attribute events to a diagnostic approach. These registry figures describe reported events; they do not establish that either test caused or prevented an event.

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

The primary posted result is a lower average time to imaging in the CCT arm than in the TEE arm, with a mean difference of -21.0 hours and a 95% confidence interval from -31.25 to -10.75 hours. This is evidence of a difference in the recorded timing outcome under the posted comparison. It describes the groups' averages and the uncertainty around their contrast.

The result does not show whether CCT and TEE are equally accurate for detecting left atrial or left atrial appendage thrombus. No diagnostic-accuracy estimates are reported in the registry information. The timing result also does not establish that a particular participant will be imaged sooner, that cardioversion will occur sooner for every participant, or that hospital admissions are reduced. Those aims appear in the registry's rationale, but are not themselves demonstrated by the primary endpoint.

The secondary time-to-cardioversion comparison has a confidence interval that includes zero. It should therefore be interpreted as uncertain about the direction and size of the average difference, rather than as a definitive confirmation of the primary timing result. Neither endpoint establishes effects on longer-term outcomes or clinical benefit beyond the measured timing intervals.

The findings also have limits as a basis for broader conclusions. The registry record does not report detailed eligibility criteria, baseline characteristics, the full analysis plan, missing-data handling, or the population included in each analysis. The record does not report a multiplicity approach or detailed results for all listed outcome measures. These gaps make it difficult to assess representativeness, robustness, and the extent to which the posted estimates reflect all randomized participants.

In general, statistical evidence about a difference is not the same as evidence that a difference is clinically important. Clinical importance depends on context not quantified by these timing summaries. The results should be understood as comparisons of the reported time measures, with their stated uncertainty and the limitations of the registry entries.

17. Why This Trial Matters Statistically

This trial addresses an important statistical distinction between a diagnostic test's accuracy and the efficiency of a care pathway in which the test is used. Its primary endpoint is time from admission to imaging, so the comparison speaks directly to process timing. The registry's rationale connects that process to cardioversion and hospital admissions, but the primary endpoint alone does not measure those broader outcomes.

The randomized parallel-group design makes a direct comparison of two imaging strategies possible. Randomization can support causal comparisons when implemented and analyzed appropriately, but the registry record does not describe the sequence generation, concealment, analysis population, or missing-data procedures. Recognizing what the design can support—and what the record does not document—is part of sound interpretation.

The primary estimate and its confidence interval communicate both direction and precision. The secondary result illustrates why related outcomes should not simply be treated as interchangeable: the group means follow a similar direction, while the secondary interval remains compatible with no mean difference. The unadjusted nature of the comparisons and the absence of a reported multiplicity plan further emphasize the need to distinguish a primary finding from secondary, potentially exploratory evidence.

Finally, the planning illustrations show how assumptions about the size of an effect influence the number of participants needed for a study. They can clarify the role of precision and detectability, but they are not a substitute for the trial's original sample-size rationale, which is not reported in the registry record. Together, these features make the trial a useful example of interpreting a process endpoint, uncertainty, secondary outcomes, and planning assumptions without extending conclusions beyond the registered measures.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry information leaves important trial and analysis details unspecified. Eligibility criteria and baseline characteristics are not reported in the registry record, so it is not possible to assess how closely the enrolled population represents other people with atrial fibrillation who are considered for cardioversion. The method of random sequence generation and allocation concealment is also not reported. Masking is listed as none, but the record does not further identify which participants or study personnel knew the assigned strategy.

The intervention descriptions are incomplete in the registry record. The TEE description includes standard tomographic planes and additional echocardiographic assessments, while the CCT description mentions non-contrast and contrast-enhanced acquisition; the full procedural details are not reported in the registry record. This limits assessment of how consistently each strategy was delivered or whether local practices affected timing.

Although the registry lists four outcome measures, full details are not reported for all measures. The primary and secondary timing outcomes are described, but diagnostic accuracy results are not reported in the information available. Nor are the definitions and handling of spontaneous cardioversion, incomplete imaging, or other pathway events fully described. The analysis population, missing-data methods, protocol deviations, and sensitivity analyses are not reported.

The record reports no analyses and does not state the original sample-size assumptions or justification. It also does not report a multiplicity plan. Consequently, the posted comparisons cannot be fully evaluated against a prespecified analysis strategy, and secondary findings require particular caution. The trial's registry status is completed, but completion status does not resolve these reporting limitations.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Left Atrial Imaging Prior to Cardioversion: Leveraging Computed Tomography to Rule Out Thrombus — NCT04223505.
• Registry record last updated 2025-03-12; status last verified 2024-09.
• Results first posted 2025-03-12.
• 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.

22. Record Summary

NCT04223505 is a completed, randomized, parallel-group trial with no masking, sponsored by Ottawa Heart Institute Research Corporation. It enrolled 102 people and compared contrast-enhanced ECG-gated cardiac CT with transesophageal echocardiography before cardioversion for atrial fibrillation. The recorded start date is 2020-06-26, and the primary completion date is 2023-11-21.

The primary outcome was time from admission to imaging, reported as a mean in hours. The posted mean was 28.1 hours for TEE and 7.1 hours for CCT; the mean difference was -21.0 hours, with a 95% confidence interval from -31.25 to -10.75 hours and an unadjusted p-value of <0.001. Time to cardioversion was listed as a secondary outcome, with a less conclusive posted comparison. The registry also reports adverse-event counts. Important details about analysis populations, missing data, multiplicity, and the original sample-size rationale are not reported in the registry record.