Arrythmia Burden in Cardiac Contractility Modulation (CCM): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Arrythmia Burden in Cardiac Contractility Modulation (CCM) (NCT05704426), a registered phase not stated study. The primary outcome is Change in Atrial Fibrillation (AF) Burden.

2. Clinical Question

The clinical question concerns a measured rhythm burden around implantation, rather than a comparison of the device against an alternative treatment. The registry notes that many device candidates already have an implanted defibrillator or permanent pacemaker, and that interrogation of such devices can provide episode data. The intended use of those records is to characterize atrial fibrillation burden before and after Optimizer implantation.

The stated objective includes evaluating atrial fibrillation episode data at least 8 months after implantation. The primary outcome description also refers to comparing the 6 months before implantation with post-implant months 3-8. These descriptions indicate the intended observation windows, but the registry does not provide participant-level timing or explain how observations were handled if follow-up differed from the described periods. The record does not report outcome values, so the clinical question cannot be answered from the posted results.

3. Trial Design

This is a retrospective and prospective evaluation of atrial fibrillation burden in relation to implantation of the Impulse Dynamics Optimizer cardiac contractility modulation device. The registry lists Hackensack Meridian Health as the sponsor, enrollment of 2, a start date of 2023-05-01, primary completion on 2023-07-18, and a status of terminated. It lists one device intervention and one primary outcome measure.

The retrospective description concerns patients with available data from the 6 months before implantation and at least 8 months after implantation when the study began. The registry's retrospective arm description is incomplete, so further eligibility details are not reported in the registry record. The prospective description concerns patients before Optimizer implantation, which would take place as part of standard care. The record does not report how many enrolled participants belonged to each group, whether any prospective participants completed post-implant follow-up, or how the two groups contributed to the primary outcome.

The planned endpoint compares each participant's pre-implant atrial fibrillation burden with post-implant burden, described as post-implant months 3-8 after a 2-month blanking period. The brief summary also describes evaluation at 8 months or greater after implantation. The registry does not clarify how those descriptions relate to the stated primary outcome timeframe of 8 months post-implantation.

The record does not describe a randomized allocation process. Its own summary identifies the study as not a randomized comparison and cautions that the arms are not a like-for-like control comparison. The retrospective and prospective groups therefore should not be read as treatment and control groups with equivalent assignment. A detailed protocol, statistical analysis plan, and reason for termination are 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

Analysis population for the primary outcome, as defined in the registry: AF burden was defined as the average minutes of AF/day. Outcome is reported at the pre implantation (pre-ccm) and at 6 months post (post ccm),

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 Change in Atrial Fibrillation (AF) Burden, measured over 8 months post optimizer implantation.

The primary endpoint is change in atrial fibrillation burden, defined as average minutes of atrial fibrillation per day. The registry describes comparing the 6 months before Optimizer implantation with post-implant months 3-8, following a 2-month blanking period. It also describes outcome reporting at pre-implantation and at 6 months post-implantation. The record does not provide the actual averages at either time or the estimated change.

As a general statistical concept, a duration-based burden measure represents how much time a rhythm is present over an observation period. It can describe more than whether an episode was recorded: the duration of episodes contributes to the average. An average expressed per day also gives a common scale for summarizing observations across a period. In this study, the stated data source is interrogation of an implanted cardiovascular device, which can record episode information.

The endpoint is relevant to the stated objective because the registry seeks to compare atrial fibrillation burden before and after Optimizer implantation. Its interpretation depends on consistent definitions of eligible episodes, observation windows, and handling of unavailable device data. Those operational details, along with any validation or quality checks, are not reported in the registry record. The endpoint definition alone does not establish what burden was observed or whether any apparent change was precise.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the outcome and intended time periods but does not report the statistical methods used to analyze participant data. In particular, the analysis model, handling of within-person measurements, assumptions, and inferential results are not reported in the registry record. The concepts below are general explanations of issues relevant to interpreting a before-and-after burden measure; they are not a description of methods confirmed for this study.

What does an average burden measure?

In general, an average is a way to summarize repeated or accumulated measurements with a single value. Here, the stated unit is average minutes of atrial fibrillation per day. That unit expresses duration on a daily scale, but the registry does not state the distribution of individual values, the number of days with usable recordings, or how days without recorded data were treated. An average alone can conceal variation: participants can have similar averages but different patterns of episodes, and a group average can differ from the experience of individual participants.

Why does the before-and-after structure matter?

As a general statistical concept, measurements from the same participant over time are related. A paired analysis can use the fact that each participant serves as their own reference, while accounting for the association between their pre- and post-period values. An analysis that treats those observations as independent would make a different assumption. The registry does not report whether the outcome was analyzed as paired participant-level data, whether the group summaries were instead compared, or whether another method was used.

Within-person comparisons can account for stable differences between participants, but they do not automatically separate an implantation-associated change from other changes over time. General threats to interpretation include changes in clinical status, concomitant care, recording duration, and availability of device data. A concurrent comparator group can sometimes help distinguish changes related to time from changes associated with an intervention, but the registry cautions that its arms are not a like-for-like control comparison. It does not report adjustment methods or a causal analysis plan.

What role do observation windows play?

The record refers to a 6-month pre-implant period and post-implant months 3-8 after a 2-month blanking period. It also describes evaluation at 8 months or greater after implantation and gives a timeframe of 8 months post-implantation. Aligning the observation windows is important in general because burden can depend on how long a participant is observed and which days are included. The registry does not explain how it handled participants with shorter or longer follow-up, incomplete recordings, or differences in the timing of interrogation.

A blanking period is a period excluded from the stated post-intervention comparison. In this record, the brief summary specifies a 2-month blanking period. As a general methodological point, excluding an initial period can define the clinical question more narrowly, but it also means the reported comparison would not describe that excluded time. The registry does not report the rationale for the blanking period or whether the exclusion was prespecified in a protocol.

How should uncertainty be considered?

In general, an estimate is more informative when accompanied by measures of uncertainty, such as a confidence interval, and by the number of observations contributing to it. A confidence interval describes uncertainty under the assumptions of the statistical method; it is not a guarantee that the true value lies within the interval. With enrollment of 2, the number of enrolled participants is limited, but the registry does not report the number with complete outcome data or any interval estimate. No uncertainty measure can be reconstructed from the record.

Over-dispersion is a general concern when observed variability is greater than a statistical model assumes. If individual burden values vary substantially, a model that assumes too little variability can overstate precision. The registry does not report a distributional model, variability estimate, or diagnostic assessment, so it is not possible to determine whether over-dispersion was considered or whether it applies to the data.

What can planning illustrations tell the reader?

The registry describes planning illustrations computed from an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event settings, the stated illustration uses a total number of events; other illustrations use participants per arm. These are planning assumptions, not a report of the study's own design, and the registry does not state the numerical planning results in the record.

In general, a sample-size calculation asks how much information would be needed to detect a specified effect under specified assumptions. Such a calculation depends on the assumed effect and variability, among other features. A planning illustration based on an observed effect is not independent confirmation of that effect and is not observed power. It does not reveal what the study actually observed, and it cannot resolve the absence of reported outcome values or analyses.

There is no reported analysis plan specifying a test, model, covariate adjustment, missing-data approach, or confidence-interval procedure. The registry also does not report interim analyses or a rationale for sample size. Without these details and without posted outcome results, the statistical methods cannot be evaluated for appropriateness or reproduced from the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, change in atrial fibrillation burden, and reports 0 analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or a multiplicity strategy. Multiplicity is a general concern when several outcomes, time points, subgroups, or statistical tests are examined: the chance of a false-positive finding can increase when many analyses are considered. The record does not establish that multiple tests were performed, so no multiplicity adjustment can be assumed or evaluated.

The registry describes pre-implant and post-implant periods, but does not report whether any additional time points or subgroup analyses were planned. Interim analyses are not reported in the registry record. It is therefore not possible to determine whether interim monitoring or any adjustment for repeated analyses was used.

Missing-data handling is also not reported. The retrospective group description requires available pre-implant and post-implant data, indicating that data availability is relevant to inclusion, but the registry does not give the number with complete measurements or the reasons data might be unavailable. It does not say whether incomplete records were excluded, imputed, or handled by another method. As a general statistical issue, missingness can affect estimates if availability is related to burden or participant characteristics; the direction and extent of any such effect cannot be determined without information about the missing observations.

The analysis populations are not reported in the registry record. There is no stated count of participants included in the primary outcome analysis, nor a description of whether the analysis used all enrolled participants, only those with complete paired data, or another population. The total enrollment of 2 does not establish the analyzed population. These omissions limit assessment of selection, attrition, and the relation between enrollment and any outcome estimate.

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

The registry record documents an intended evaluation of average atrial fibrillation burden before and after implantation of the Impulse Dynamics Optimizer device. It also documents enrollment of 2 and a terminated status. It does not report the outcome values or an analysis result. Consequently, the posted information does not show whether the measured burden increased, decreased, or remained similar, and it does not show how precise any estimated change would be.

This absence of a reported result should not be mistaken for a finding of no change. A missing estimate is different from an estimate near zero, and the record supplies no confidence interval or other uncertainty measure that could distinguish between those situations. Nor does the record establish that data were collected for every enrolled participant or that any particular analysis was completed.

The study design also does not support reading the prospective and retrospective arms as randomized treatment and control groups. The registry itself notes that the allocation is not stated and that the arms are not a like-for-like control comparison. General causal interpretation of an observed before-and-after difference would require attention to other changes over time and to who had usable records. The registry does not report methods that would address these issues.

The adverse-event entries list zero participants at risk in the Retrospective group, alongside zero recorded serious events, other events, and deaths. Because the listed at-risk count is zero, those entries cannot establish an absence of adverse events in the enrolled population or quantify safety. They are registry entries with no interpretable participant denominator in that group.

The most defensible conclusion is therefore limited: the record states a clinically defined measurement question and gives a basic description of the intended comparison, but it does not provide results that answer that question. No efficacy, lack-of-effect, precision, or safety conclusion should be inferred from the absence of posted estimates.

12. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in clinical device research: a data source may allow repeated measurement of a clinical feature, while the design and reporting still determine how confidently a change can be interpreted. Device interrogation can supply episode data, and average minutes of atrial fibrillation per day gives the intended outcome a duration-based scale. Those features make the endpoint understandable, but they do not by themselves establish completeness, comparability, or causal attribution.

For a before-and-after evaluation, the relationship between measurements from the same participant matters. General statistical methods can account for paired observations, but a credible interpretation also depends on well-defined observation periods and transparent reporting of participant-level availability. The registry describes a pre-implant window, a post-implant window, and a blanking period, but does not report the analysis details or outcome data needed to assess how those design features were implemented.

The enrollment of 2 and the terminated status underscore why reporting the number actually analyzed, the individual or group summaries, and uncertainty is important. Without those details, readers cannot distinguish a lack of information from a precisely estimated small change, and cannot assess whether the intended comparison was feasible. The planning assumptions described in the registry do not answer that question; planning illustrations are not observed findings.

The record is also a reminder that an adverse-event count needs a clear denominator. Zero events alongside zero participants at risk cannot be interpreted as a demonstrated absence of harm. Clear participant flow and outcome reporting are essential both for clinical interpretation and for statistical evaluation.

13. Limitations

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

The principal limitation for statistical interpretation is that the registry record does not report the primary outcome values or an analysis. It gives an endpoint definition and time period, but no pre-implant or post-implant averages, estimated change, uncertainty interval, or test result. There is consequently no quantitative result to interpret.

Enrollment is 2, and the study is listed as terminated. The record does not give the number of participants contributing usable paired outcome data, the distribution of enrollment across study groups, or participant flow. It is not possible to determine whether the outcome definition was applied to all enrollees or only to a subset. The reason for termination is not reported in the registry record.

The design is not a randomized comparison, and the registry cautions that the retrospective and prospective arms are not like-for-like control groups. The retrospective arm description is incomplete. The record does not report how differences in participant characteristics, follow-up, or clinical care were handled, or whether any adjustment was planned.

The timing descriptions do not fully explain how the stated post-implant outcome timeframe relates to the evaluation at 8 months or greater after implantation. The registry does not describe the handling of variable follow-up or incomplete device records. Definitions for episode processing, quality control, and missing data are also not reported in the registry record.

Finally, the adverse-event entry lists 0 participants at risk in the Retrospective group, so its zero event counts do not provide a meaningful safety denominator. Taken together, the limited enrollment, terminated status, missing outcome results, and absent analysis details sharply restrict what can be concluded from this record.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Arrythmia Burden in Cardiac Contractility Modulation (CCM) — NCT05704426.
• Registry record last updated 2024-08-19; status last verified 2024-03.
• Results first posted 2024-08-19.
• 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.

17. Record Summary

NCT05704426, titled Arrythmia Burden in Cardiac Contractility Modulation, is a retrospective and prospective evaluation sponsored by Hackensack Meridian Health. It lists enrollment of 2, a start date of 2023-05-01, primary completion on 2023-07-18, and a status of terminated.

The study concerns the Impulse Dynamics Optimizer cardiac contractility modulation device. Its primary outcome is change in atrial fibrillation burden, defined as average minutes of atrial fibrillation per day. The intended comparison is between the 6 months before implantation and post-implant months 3-8 after a 2-month blanking period. The record also describes evaluation at 8 months or greater after implantation.

The registry lists one outcome measure and 0 analyses. It does not report outcome values, an estimated change, or inferential results. It describes the comparison as nonrandomized and cautions that the arms are not a like-for-like control comparison. Group-specific enrollment, missing-data handling, analysis populations, and the reason for termination are not reported in the registry record.