Conduction System Pacing Optimized Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Conduction System Pacing Optimized Therapy (NCT04905290), a na na study. The primary outcome is Electrical Synchronization Response.

2. Clinical Question

The central statistical question is a comparison among pacing configurations, not a comparison between independently randomized groups. The registry describes each participant undergoing three pacing configurations during the acute protocol and reports that within each participant, differences were formed between CSPOT and CSP and between CSPOT and BiV. The mean of those differences was the intended primary summary.

SDAT, or Standard Deviation of Activation Times, is an ECG-belt measurement of electrical dyssynchrony. The registered primary endpoint is the difference in percent change in SDAT, with the percent change calculated from AV-only pacing across five AV delays. The endpoint therefore targets an acute electrical response, rather than a long-term clinical outcome.

The study also lists outcomes including left ventricular ejection fraction, left ventricular end systolic volume, a clinical composite score, and subgroup measures. The registry record does not report numerical results for the primary comparison, so the direction and size of any observed difference cannot be described from that record.

3. Trial Design

CSPOT (NCT04905290), the Conduction System Pacing Optimized Therapy Study, is recorded as a completed, single-group device study in people with heart failure. Enrollment was 60. The recorded start date was 2021-11-27, and primary completion was 2023-04-18. The listed phase and allocation are NA, and masking is listed as none.

The study purpose was to examine which mode of cardiac resynchronization therapy pacing might be appropriate for different populations of CRT patients, comparing traditional BiV pacing, CSP-only pacing, and CSPOT, which combines CSP and left ventricular pacing. The registry also states that system safety would be assessed. The interventions are described as device configurations: left ventricular coronary sinus (BiV), CSP-only, and CSPOT.

The single-arm description says participants underwent CSPOT lead placement, an acute pacing protocol, and then device implantation. During the acute protocol, participants underwent the three pacing configurations. The primary endpoint description further specifies that percent change in SDAT from AV-only pacing was calculated for each participant-configuration combination across five AV delays. The primary analysis definition then uses within-participant differences, comparing CSPOT with CSP and CSPOT with BiV.

This structure permits a paired, within-participant comparison of acute measurements. It does not create randomized parallel groups, and allocation is recorded as NA. The record specifically cautions that the arms are not a like-for-like control comparison. The registry record does not report details of sequence assignment, a randomization procedure, or whether configuration order was varied.

The registry lists eleven outcome measures, including electrical, cardiac-function, clinical-composite, and subgroup outcomes. It records zero analyses. The detailed statistical analysis plan, including any prespecified handling of missing measurements or multiplicity, is not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects with SDAT measurements available for each pacing configuration.

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 Electrical Synchronization Response, measured over At implant during acute protocol.

The primary endpoint is titled Electrical Synchronization Response and is expressed as a difference in percent change in SDAT. SDAT is the Standard Deviation of Activation Times measured by an ECG belt and described as a measure of dyssynchrony. For each participant and pacing configuration, percent change from AV-only pacing was calculated over five AV delays. The within-participant difference between CSPOT and CSP, and separately between CSPOT and BiV, was then calculated. The endpoint summary is the mean of these differences, with a 95% confidence interval.

This endpoint focuses on an acute electrical measurement during pacing, rather than a long-term health outcome. Comparing measurements within the same participant can account for stable characteristics shared across that participant’s measurements. The resulting mean describes the average paired difference in the analyzed participants; it does not by itself establish what caused the difference or what it means for longer-term clinical outcomes.

The endpoint is defined for participants with SDAT measurements available for each pacing configuration. The registry record does not report the number of participants with complete measurements, the mean paired differences, or their confidence intervals. It also does not report a threshold for interpreting a difference as clinically important. Consequently, the registry record alone does not show the magnitude or precision of the primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry’s primary endpoint is a continuous measure, and the parameter is the mean. The analysis begins with percent change in SDAT from AV-only pacing for each participant and pacing configuration, calculated over five AV delays. It then forms two participant-level contrasts: CSPOT versus CSP, and CSPOT versus BiV. The mean of each set of paired differences is the primary summary, with a 95% confidence interval specified for each comparison.

Why use within-participant differences?

In general, a paired analysis compares two measurements from the same participant rather than treating them as if they came from unrelated people. Measurements from one participant may be more alike because they share characteristics and circumstances. Taking the difference within each participant focuses the comparison on how the measured response varies between configurations for that participant. Averaging those differences estimates the mean paired contrast in the participants included in the analysis.

Pairing does not guarantee that all sources of bias are removed. For example, measurement order or protocol-related changes could matter if they influence the response. The registry record describes the pacing configurations and the paired calculation, but does not report whether configuration order was randomized or otherwise accounted for, or the exact statistical model used to calculate the confidence intervals.

What does the confidence interval convey?

In general, a confidence interval gives a range of values compatible with the estimate and the statistical method’s assumptions. It communicates precision: estimates with wider intervals are less precisely determined than estimates with narrower intervals. It is important to consider both the estimated contrast and the interval, rather than treating the interval as a yes-or-no test. The registry record specifies a 95% confidence interval but does not report its limits or the underlying mean differences.

The registry describes SDAT as a measure of dyssynchrony, but does not state a clinical threshold for the size of a meaningful change. Statistical precision and clinical importance are different questions. Even if an estimate and interval were available, interpretation would require context about meaningful differences; that context is not reported in the registry record.

What is known about the analysis population?

The primary population is defined as participants with SDAT measurements available for every pacing configuration. This complete-measurement requirement means the analysis population may not be identical to the enrolled population. The total enrollment is 60, but the number meeting this endpoint-specific requirement is not reported in the registry record. The record also does not describe reasons for missing measurements or how incomplete sets were handled.

In general, missing data can affect both precision and the interpretation of an estimate, particularly if the participants with observed measurements differ systematically from those without them. A complete-case analysis describes participants with the required measurements; its generalizability depends partly on why other measurements are unavailable. No missing-data assumptions or sensitivity analyses are reported in the registry record.

How should planning illustrations be read?

Sample-size illustrations use the observed effect as a planning reference and assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect to detect is expressed as a fraction of the observed effect. For non-time-to-event outcomes, the illustration is stated as participants per arm for a target power; time-to-event illustrations are stated as total events.

These are planning illustrations, not evidence of the study’s original design rationale, and not observed power. The registry record does not report the study’s own sample-size justification. Because the numerical illustrations and observed primary effect are not reported in the registry record, no specific planning sample size or effect magnitude can be stated. Moreover, the illustrations’ two-arm equal-allocation assumptions do not describe this single-group, within-participant acute protocol as recorded.

What statistical plan is recorded?

The record provides the primary endpoint definition and lists secondary outcomes, but does not provide a full statistical analysis plan. It records zero analyses. Details such as the exact confidence-interval procedure, model diagnostics, handling of multiple outcomes, subgroup analysis methods, and prespecified sensitivity analyses are not reported in the registry record. In general, these details help readers assess whether an analysis matches its intended question and how robust the conclusions may be; they should not be inferred from the endpoint definition alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eleven outcome measures, including SDAT-based subgroup outcomes, cardiac-function measures, and a clinical composite score. It does not report how the primary and secondary outcomes were prioritized for inference, whether any multiplicity adjustment was planned, or how subgroup analyses were to be interpreted. When several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. In general, a prespecified multiplicity strategy can help control that concern, but no such strategy is reported in the registry record.

The primary endpoint includes two contrasts: CSPOT versus CSP and CSPOT versus BiV. The registry describes the paired differences and their mean with 95% confidence intervals, but does not report whether the two contrasts were treated as co-primary, whether one was primary and the other supportive, or how their joint interpretation was planned.

The primary analysis population requires SDAT measurements for each pacing configuration. The registry record does not report the number of participants with complete measurements, the reasons for any missing measurements, or a missing-data method. It also does not describe whether all enrolled participants were included in safety summaries or how analysis populations were defined for other outcomes.

These omissions matter because an endpoint estimate depends on which observations are analyzed and how uncertainty is calculated. In general, incomplete data can reduce precision and can affect interpretation if availability is related to participant characteristics or response. Without a reported analysis population count, missing-data strategy, and multiplicity plan, the numerical inferential framework cannot be fully assessed. The registry lists zero analyses, so these details cannot be resolved from posted analysis results.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac perforation (3.3%), pericarditis (3.3%), vascular pseudoaneurysm (3.3%), thrombocytopenia (1.7%), acute myocardial infarction (1.7%).

The registry records a single arm with 60 participants at risk for serious adverse events and 20 affected, 60 at risk for other adverse events and 14 affected, and 2 deaths. The selected serious adverse-event terms and their recorded percentages are cardiac perforation, 3.3%; pericarditis, 3.3%; vascular pseudoaneurysm, 3.3%; thrombocytopenia, 1.7%; acute myocardial infarction, 1.7%; and arrhythmia, 1.7%.

These are descriptive figures for the study group. The serious and other adverse-event counts refer to affected participants in the registry’s single-arm summary; the selected terms are listed with percentages. The record does not establish whether events were caused by a device configuration, nor does it provide a randomized comparator for interpreting rates comparatively. It also does not give enough detail in the posted summary to determine event timing, duration, severity beyond the serious classification, or whether participants could contribute more than one event category.

Deaths are recorded separately as 2. The registry record does not provide further information about their causes or relationship to study participation. These safety data should therefore be read as counts and selected event terms recorded during the study, not as proof of causation or a comparative safety estimate.

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

The study is designed to characterize acute electrical synchronization during three pacing configurations. Its primary endpoint uses paired differences in percent change in SDAT, a measurement described as reflecting dyssynchrony. The registry record explains the intended comparison, but does not report the mean differences or their confidence intervals. Thus, the posted record does not establish the direction, size, or precision of the primary result.

Even with a numerical SDAT estimate, an acute electrical measure would answer a narrower question than whether a configuration changes longer-term health outcomes. The registry lists left ventricular ejection fraction, left ventricular end systolic volume, and a clinical composite score among the secondary outcomes, but numerical results for these outcomes are not reported in the registry record. The relationship between acute SDAT differences and those outcomes cannot be determined from the record.

The single-group structure is important to interpretation. Participants underwent multiple pacing configurations in an acute protocol, allowing within-participant measurement contrasts. This is not a randomized comparison of separate groups receiving different therapies. The registry record cautions that the arms are not like-for-like control comparisons; configuration contrasts should be understood as acute, paired measurements rather than independent-group treatment effects.

The recorded safety figures describe adverse events and deaths in the study group. Without a control group and additional causal information, they do not quantify whether an event was attributable to a particular configuration or estimate a comparative safety difference.

In short, the registry record documents the question, the measurement approach, and descriptive safety counts, but not the numerical primary efficacy result. It cannot support conclusions about the size or clinical importance of an acute difference, longer-term outcomes, or comparative safety.

13. Why This Trial Matters Statistically

This study raises a useful statistical design question: how to compare several acute measurements collected from the same participant. The registered primary analysis uses within-participant differences rather than treating each pacing configuration as an independent group. In general, this approach can account for shared participant characteristics and directly target the average contrast between configurations.

The endpoint also illustrates the distinction between a measurement and a clinical outcome. SDAT is described as an ECG-belt measure of dyssynchrony, while the listed secondary outcomes include cardiac-function measures and a clinical composite score. Those outcomes address different aspects of the study question. They should not be treated as interchangeable, and an acute electrical endpoint alone does not provide a numerical answer about longer-term clinical outcomes.

The registry record’s missing primary estimate and confidence interval are statistically consequential. Without them, readers cannot assess the observed direction, magnitude, or precision of the primary contrasts. The record also lists eleven outcome measures but does not describe a multiplicity strategy, analysis population counts, or missing-data methods. These details are relevant to judging how the analyses were defined and how uncertainty should be interpreted.

The study is single-group, with allocation listed as NA, and its comparisons are not like-for-like control comparisons. This makes it especially important to distinguish paired acute configuration contrasts from randomized between-group evidence. The design can address the registered acute measurement question, but it does not, on its own, supply a controlled comparison of long-term treatment effects.

Finally, the safety summary emphasizes the value of separating descriptive event reporting from causal or comparative claims. Counts and selected terms provide a record of events, but a single-arm summary cannot by itself estimate what would have occurred under a different configuration.

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 main limitation for statistical interpretation is that the registry record does not report the numerical primary endpoint estimates or their 95% confidence intervals. It also records zero analyses. Consequently, readers cannot assess the observed direction, magnitude, precision, or statistical compatibility of the primary comparisons from the registry record.

The study is recorded as single-group, with allocation listed as NA and no masking. Its primary comparisons are within-participant acute measurements across pacing configurations, rather than randomized comparisons between independent groups. The registry specifically notes that the arms are not like-for-like control comparisons. The record does not report whether the configuration sequence was randomized or how order-related effects were handled.

Although enrollment was 60, the endpoint population is restricted to participants with SDAT measurements available for every configuration. The number meeting that requirement, the completeness of measurements, and the reasons for missing data are not reported. The statistical analysis plan and details of the confidence-interval calculation are also not reported in the registry record.

The registry lists eleven outcomes, but does not state how multiplicity was handled or how subgroup analyses were prespecified. It does not provide a study-specific sample-size justification. The sample-size assumptions described for planning illustrations are not the same as the trial’s original design rationale, and the numerical illustration results are not reported in the registry record.

Finally, the primary endpoint is acute and electrical, while longer-term clinical interpretation would require outcome results and context not reported in the record. The safety information is descriptive and lacks a control-group comparison and further event-level context. These limitations restrict what can be concluded from the registry entry, independent of the intended study question.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Conduction System Pacing Optimized Therapy — NCT04905290.
• Registry record last updated 2025-04-15; status last verified 2023-10.
• Results first posted 2025-01-17.
• 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

NCT04905290 is the completed CSPOT single-group device study in people with heart failure. Enrollment was 60; the recorded start date was 2021-11-27 and primary completion was 2023-04-18. Masking is listed as none, and allocation and phase are listed as NA.

The primary endpoint is the mean paired difference in percent change in SDAT for CSPOT compared with CSP and with BiV during an acute pacing protocol, with a 95% confidence interval specified. The registry record does not report the numerical primary result or confidence interval and lists zero analyses.

The safety summary records 20 participants affected by serious adverse events, 14 by other adverse events, and 2 deaths in the single arm. The listed serious-event terms are descriptive and do not establish causation. The registry lists eleven outcome measures but does not report a complete statistical analysis plan, missing-data approach, or multiplicity strategy.