Cardiac Electrophysiological Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cardiac Electrophysiological Study (NCT00616629), a randomized phase 2 study. The primary outcome is LAERP (Left Atrial Effective Refractory Period (ie, the Longest S1-S2 Interval That Fails to Result in Atrial Depolarisation)).

2. Clinical Question

3. Trial Design

This is a Phase II, randomized, double-blind study of AZD1305 in participants undergoing an invasive electrophysiological procedure. The official title describes it as multi-centre, placebo-controlled, and single-dose. The trial status is completed. The record lists enrollment of 55, a start date of 2008-01, and primary completion in 2008-06.

The reported groups are AZD1305 Dose Group 1, AZD1305 Dose Group 2, AZD1305 Dose Group 3, AZD1305 Dose Group 4, and placebo. The primary endpoint results use group denominators of 11, 11, 13, 2, and 11, respectively. The registry's design metadata also classifies the model as single-group. That classification sits alongside the randomized, placebo-controlled title and the displayed results for multiple groups; the record does not explain this difference in classification.

The primary measurement was obtained before infusion and again 20 min (or more) after the start of administration. The record does not give a more exact measurement time for each participant. It identifies AZD1305 as the drug intervention but does not report dose amounts, a detailed allocation procedure, the randomization ratio, or further masking procedures. The listed study population is participants with atrial flutter undergoing an invasive electrophysiological procedure; eligibility criteria beyond this are not reported in the registry record.

The trial also lists electrocardiographic and electrophysiological variables, drug exposure measures, and adverse events among its outcomes. The registry record reports no analyses for the primary endpoint. Accordingly, the posted primary results describe group-level changes rather than a reported inferential comparison between AZD1305 and placebo.

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: At the pre-entry visit, which took place within 14 days before the planned catheter ablation (Study Day), patients underwent a full clinical assessment including a physical examination, ECG recording, Bood pressure(BP)/heart rate measurement, routine laboratory tests, and transthoracic echocardiography (TTE, if not done within the prior 6 months).

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 LAERP (Left Atrial Effective Refractory Period (ie, the Longest S1-S2 Interval That Fails to Result in Atrial Depolarisation)), measured over Measurements were obtained twice, from the invasive electrophysiological measurements made before and 20 min (or more) after the start of administration of the investigational product.

Left atrial effective refractory period, or LAERP, is defined in the registry as the longest S1-S2 interval that fails to result in atrial depolarisation. It is a measure of the timing properties of atrial tissue during electrophysiological testing. The endpoint is reported in milliseconds, with measurements made before and after infusion during the invasive procedure.

The primary outcome is the absolute change calculated as after minus before infusion. A positive change therefore represents a higher post-infusion value than the pre-infusion value; a negative change represents a lower value. This describes the direction of the measured change and does not, by itself, establish a treatment effect. Interpreting a treatment effect would require an appropriate comparison between randomized groups, with an estimate of uncertainty and an analysis approach.

The record reports the mean and full range for each group. A mean gives a measure of the group's average change, while the full range gives the lowest and highest reported changes. The range conveys how far apart the observed values extend, but it does not quantify the precision of the mean in the way a confidence interval would. The registry record does not report a confidence interval or a primary between-group analysis for LAERP.

LAERP is used as a physiological measurement relevant to the study's stated aim of assessing cardiac electrophysiological properties. It is not itself a patient-centred clinical outcome. The registry record does not establish how a change in this measure relates to symptoms or longer-term clinical outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome summaries describe changes in LAERP from before to after infusion. The registry defines the change as after minus before, so the sign indicates the direction of the within-participant change. The record reports a mean and full range by group. It does not report a standard deviation, standard error, confidence interval, or inferential analysis for this primary endpoint.

What does the mean describe?

General statistical explanation: the mean is the arithmetic average of the observed changes in a group. It condenses the results to one central value, but it can be influenced by unusually large or small observations. A group mean does not show whether most individuals changed by a similar amount, nor does it show the precision of that mean. The range gives the endpoints of the observed values, but not how observations are distributed between those endpoints.

In this record, the primary endpoint is measured in milliseconds, and the reported summaries use a full range. The range is not a confidence interval: it describes the observed spread of values rather than a range of plausible values for the underlying group mean. Because a confidence interval and a primary comparison are not reported, the primary summaries alone cannot support a formal conclusion about the difference between AZD1305 and placebo.

How should the secondary binary comparisons be read?

The secondary outcome “Number of Patients Who Had at Least One AE” is a binary outcome: each participant either had at least one adverse event during the active treatment period or did not. The posted comparisons use risk differences for Dose Group 1 versus placebo and Dose Group 2 versus placebo. A risk difference expresses the difference between the observed proportions in the two groups. General statistical explanation: unlike a ratio measure, a risk difference is expressed on an absolute scale, making its direction and magnitude tied to the difference in event frequency between groups.

The registry also posts unadjusted p-values of 0.484 and 0.537 for these comparisons. A p-value describes how compatible the observed data are with a specified null hypothesis under the test's assumptions; it is not the probability that the null hypothesis is true. These p-values do not by themselves express the size or precision of an effect. The posted intervals for the risk differences include zero, so they do not rule out no difference. The registry record does not report a multiplicity adjustment or a reported analysis plan for these secondary comparisons.

What do the planning illustrations mean?

The sample-size illustrations are based on the observed effect, not on the trial's original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations consider planning for 100%, 75%, or 50% of the observed effect. For the comparison of Dose Group 1 with placebo, the listed values are 185 and 248 participants per arm for 80% and 90% power when planning for 100% of the observed effect; 304 and 406 for 75%; and 623 and 833 for 50%. For Dose Group 2 versus placebo, the corresponding figures are 247 and 329 for 100%, 407 and 544 for 75%, and 843 and 1,128 for 50%.

These are planning illustrations, not observed enrollment targets or results from a power analysis conducted for the trial. They do not show that the original study had a particular power. General statistical explanation: planning calculations depend on assumptions about the effect to detect, the statistical test, and the design. Using a noisy observed effect as the starting point can make an illustration unstable, especially when group sizes are small. The registry record does not report the trial's own sample-size justification.

Why does group size matter?

General statistical explanation: smaller groups generally provide less information about the distribution of outcomes and can yield less precise estimates. That limitation is particularly important for Dose Group 4, whose primary endpoint denominator is 2. The group summaries remain descriptive, but they should not be treated as precise estimates of what would occur in a larger population. Differences between descriptive means also need to be considered in light of variability, which the primary record summarizes only through the full range.

The record's outcome summaries and analysis metadata do not identify a primary statistical model, covariate adjustment, handling of missing measurements, or analysis population. Those methods are not reported in the registry record, so no assumptions about them can be used to interpret the posted results.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcome domains and reports two unadjusted comparisons for the binary adverse-event outcome. It does not report a multiplicity strategy, such as an adjustment to account for testing several outcomes, a prespecified hierarchy, or a distinction between confirmatory and exploratory analyses. The record also lists zero analyses for the primary endpoint and no reported analyses for the secondary outcome comparisons. As a result, the posted p-values should not be treated as evidence from a fully described confirmatory testing program.

Missing-data procedures are not reported in the registry record. It does not explain whether all randomized participants were expected to contribute to each endpoint, how missing measurements were handled, or whether any imputation was used. The primary group denominators are reported, but the record does not explain why they differ across groups or how those denominators relate to the overall enrollment figure. The number of participants with outcome data may differ from enrollment, and the record does not provide enough detail to determine the reasons.

The analysis populations are also not reported in the registry record. There is no stated intention-to-treat, per-protocol, or other population definition for the primary endpoint or secondary comparisons. The record does not identify whether the analyses followed randomized assignment or whether participants were excluded from any outcome analysis.

These omissions limit reproducibility and interpretation. They do not show that a particular procedure was or was not used; they mean the registry record does not document it. Without a reported analysis population, missing-data approach, and multiplicity plan, the posted summaries and unadjusted comparisons should be treated as descriptive and interpreted cautiously.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bradycardia and hypotension (8.3%).

The serious adverse event record reports affected-participant counts by group. The counts are 0 of 11 in AZD1305 Dose Group 1, 1 of 12 in Dose Group 2, 1 of 13 in Dose Group 3, 0 of 2 in Dose Group 4, and 1 of 12 in placebo. These are group-level counts, not comparative estimates adjusted for differences in group size or uncertainty.

The registry identifies “Bradycardia And Hypotension” as a serious adverse event term and reports 8.3% for that term. The record does not give enough information to assign that term to a particular treatment group or to interpret the percentage's denominator. The number of deaths and the number at risk for other adverse events are not reported in the registry record.

General statistical explanation: serious adverse events are uncommon outcomes for which small group counts can be especially imprecise. A count of zero in a small group does not establish that the event cannot occur, and a count in one group does not establish a difference from another group. The registry record does not provide a formal comparative safety analysis or enough detail about event timing and attribution to support broader conclusions.

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

The primary outcome is a physiological measurement taken during an invasive electrophysiological procedure. The posted group summaries show the average change in LAERP after infusion and the full range of observed changes in each reported group. They provide a descriptive account of what was recorded in this trial, not a definitive estimate of a treatment effect.

The registry record does not report a primary comparison, confidence interval, or analysis method for LAERP. It therefore does not establish whether the observed group means differ beyond what could be expected from variability. A range of participant-level observations is not a substitute for an uncertainty interval around a group comparison. The small denominators, particularly the denominator of 2 in Dose Group 4, further constrain how broadly the summaries can be interpreted.

The study title and intervention description identify an investigation of AZD1305 given as a single intravenous infusion in participants undergoing a procedure. The outcome is a short-term electrophysiological measurement, obtained before and 20 min (or more) after administration. The registry record does not report longer-term clinical outcomes or establish how changes in LAERP relate to them.

The secondary adverse-event comparisons are unadjusted, and the record does not report a multiplicity strategy. Their p-values and intervals should not be read as evidence of equivalence or as a complete assessment of safety. Serious-event counts are also sparse, and key safety details are not reported in the registry record.

In practical statistical terms, the posted results are useful for understanding which measurements were collected and the observed group summaries. They do not, on their own, establish a clinically meaningful benefit, lack of benefit, or comparative safety profile. Such conclusions would require adequately described analyses, uncertainty estimates, and supporting clinical context that the registry record does not report.

13. Why This Trial Matters Statistically

This trial illustrates the difference between a randomized design and a fully reported comparative analysis. The official title describes randomization, masking, and placebo control, and the posted primary data include several AZD1305 dose groups plus placebo. Yet the registry reports group summaries for the primary endpoint without a primary between-group analysis. Randomization can support fair comparisons when analyzed and reported appropriately, but it does not make descriptive group means equivalent to an inferential comparison.

The outcome itself also highlights the distinction between measurement and clinical interpretation. LAERP is a defined electrophysiological measure, recorded before and after infusion. A change in that measure is not automatically a change in a clinical outcome. The record does not report how the observed changes relate to symptoms or longer-term outcomes, so the statistical meaning of the endpoint should be kept separate from claims about clinical consequences.

The different denominators and the very small Dose Group 4 provide a concrete reminder that group-level precision depends on the available information. The planning illustrations further show how assumed effect size affects hypothetical sample-size requirements. They should not be mistaken for observed power or for the trial's original design justification; that justification is not reported in the registry record.

Finally, several secondary outcomes are named, while numeric results and analyses are limited in the registry record. This underscores why complete outcome reporting, transparent analysis populations, missing-data methods, and multiplicity plans matter. Without those details, readers can describe the posted results but cannot reconstruct a comprehensive inferential analysis.

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.

Several limitations specific to this record affect interpretation. First, the primary endpoint is reported descriptively, with no statistical analysis, confidence interval, or between-group estimate. The reported means and full ranges therefore do not quantify the precision of the differences between AZD1305 and placebo.

Second, group sizes are small and unequal, and Dose Group 4 has a primary endpoint denominator of 2. Its mean and range are consequently especially limited as summaries of a wider population. The record does not provide standard deviations or other measures that would allow a fuller assessment of within-group variability.

Third, there is a mismatch between the registry's single-group model classification and the randomized, placebo-controlled title and displayed multiple-group results. The record does not explain the classification. Dose amounts, detailed eligibility criteria, randomization procedures, and further allocation information are also not reported in the registry record.

Fourth, the time window is described as before infusion and 20 min (or more) after the start of administration. The exact timing for each measurement is not specified. The primary endpoint is a short-term physiological measurement, and longer-term outcomes are not reported in the posted results.

Finally, the registry does not report the primary analysis method, analysis populations, missing-data procedures, or multiplicity plan. Numeric results for most listed secondary outcomes are not reported in the registry record, and the safety record leaves some details, including deaths and other-event denominators, unreported. These limits prevent a comprehensive assessment of efficacy, safety, or the robustness of the findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cardiac Electrophysiological Study — NCT00616629.
• Registry record last updated 2011-09-22; status last verified 2011-08.
• Results first posted 2011-09-22.
• 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

The registry record for NCT00616629 describes a completed Phase II study of AZD1305 in participants with atrial flutter undergoing an invasive electrophysiological procedure. The official title identifies a multi-centre, double-blind, randomized, placebo-controlled, single-dose study. The record lists enrollment of 55, a start date of 2008-01, and primary completion in 2008-06.

The primary endpoint is absolute change in left atrial effective refractory period, measured in milliseconds before and after infusion. Results are reported as group means and full ranges for four AZD1305 dose groups and placebo. The registry record does not report a primary statistical analysis. Secondary outcomes cover electrophysiology, electrocardiography, AZD1305 exposure, and adverse events; numeric reporting is limited, and the record lists no reported analyses.

The posted data support descriptive interpretation of the recorded measurements, not a definitive comparative conclusion. Analysis populations, missing-data procedures, multiplicity methods, and the trial's sample-size justification are not reported in the registry record.