Advance Cardiac Resynchronization Therapy (CRT) Registry: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Advance Cardiac Resynchronization Therapy (CRT) Registry (NCT01805154), a registered phase not stated study. The primary outcome is Number of Subjects Who Had an Improvement in NYHA Class Between Six Months and 12 Months.

2. Clinical Question

The registry concerns real-world care of cardiac resynchronization therapy (CRT) patients, with particular interest in how clinicians define and manage non-responders. Its primary outcome is a count of participants whose NYHA class improved by at least one class between six and 12 months. The record does not give the number who met that definition, so the amount of improvement cannot be stated from the primary outcome details available in the registry record.

The stated intent is descriptive: to understand CRT care strategies in clinical practice, especially for patients regarded as non-responders. The registry record does not define a separate non-responder subgroup for this outcome or report how clinicians applied that label. The question therefore concerns the recorded class-change outcome among evaluable participants, rather than the effectiveness of one treatment strategy relative to another.

3. Trial Design

NCT01805154, titled the Advance Cardiac Resynchronization Therapy (CRT) Registry, is listed as completed. The sponsor is Abbott Medical Devices. The record gives a start date of 2013-01 and a primary completion date of 2016-11. Enrollment is 1529. The brief description says the registry aimed to understand comprehensive clinical care strategies for CRT patients, particularly non-responders, in real-world practice.

The listed intervention is “CRT Patients,” classified as a device. The arm description specifies patients who had received any market-approved St Jude Medical CRT-D or CRT-P device. The record does not describe a randomized treatment assignment. Allocation is not stated, and the record does not identify a control group suitable for a like-for-like comparison. The registry should therefore be read as a description of patients and outcomes in clinical care, not as a randomized estimate of the effect of CRT versus another approach.

Four outcome measures are recorded, while the number of analyses is listed as zero. The primary outcome is the number of subjects with an improvement in NYHA class between six and 12 months, defined as an improvement by at least one class. The primary outcome’s analysis population is restricted to participants with evaluable data at both time points. The record notes that this population is smaller than the group that completed both visits, but does not state the analyzable count.

The registry record does not report a detailed statistical analysis plan, an allocation procedure, or how the clinical-care strategies were selected. It also does not report a sample-size justification. These omissions limit what can be inferred about planning and analysis. The status “completed” describes the registry’s recorded status; it does not by itself establish that every planned outcome was reported or that all enrolled participants contributed evaluable data to each outcome.

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: The analysis population included any subject who had a 6-month CRT evaluation or died due to a cardiovascular cause prior to 6 months. Subjects who withdrew prior to the 6-month visit, did not complete the 6-month visit or had relevant 6-month data missing were excluded from the analysis.

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.

Population: Of 1529 subjects enrolled, 5 were not included in baseline analyses (1 subject had incomplete informed consent and 4 did not have a device implant). Thus, only 1524 subjects were evaluable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Who Had an Improvement in NYHA Class Between Six Months and 12 Months, measured over Between 6 and 12 months.

The primary endpoint counts participants whose NYHA class improved by at least one class between six and 12 months. NYHA class is used to describe the degree of limitation associated with heart failure symptoms in ordinary activity. In this registry, the endpoint is defined as a change in class over a specified follow-up interval, rather than a measure of device use or a direct comparison between assigned treatments.

A class-based outcome can make a clinical change easier to describe than an unstructured impression because the endpoint specifies a threshold: improvement of at least one class. A count can also communicate how many people in the evaluable group met that threshold. General: any threshold-based outcome depends on the definition and assessment of the categories, so the interpretation is tied to the stated threshold and the quality and completeness of measurements at both time points.

The endpoint is limited to participants with evaluable data at both six and 12 months. The registry record explicitly notes that fewer participants were analyzable than completed the visits. It does not report the number with evaluable data, the number who improved, the number whose class was unchanged or worsened, or an uncertainty interval for the count. Thus, the endpoint definition is available, but its numerical result and precision are not reported in the registry record.

The outcome is descriptive in this setting. Without a comparable control group and an analysis that accounts for treatment assignment, the count cannot isolate a treatment effect. It records how often the defined class improvement was observed in the participants with evaluable measurements.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: statistical methods determine how observations are summarized, how uncertainty is represented, and whether comparisons can be interpreted as estimates of effects. The registry record gives a primary outcome definition and several safety counts, but it does not report a detailed statistical analysis plan or outcome analyses. The explanations below distinguish what the design and outcome definition imply from what is not reported in the registry record.

What does a participant count represent?

The primary outcome is a count of participants who improved by at least one NYHA class between six and 12 months. A count answers how many people met a definition; it does not, by itself, state the proportion of an analysis population, the size of a treatment effect, or the uncertainty around that effect. To interpret a count fully, readers need its denominator and the way participants with missing or unevaluable measurements were handled. The registry record restricts the endpoint to those with evaluable data at both time points, but the size of that group and the outcome count are not reported.

General: if an outcome is analyzed as a proportion, the denominator should correspond to the population from which the event count was obtained. If participants are excluded because measurements are missing, the resulting description applies directly to those analyzed. Whether it also represents all enrolled participants depends on why data are missing and on the analysis assumptions. The reasons for missing or unevaluable NYHA measurements are not reported in the registry record.

Why does the design matter?

Random assignment can help make groups comparable at the start of a study, on average, for measured and unmeasured factors. This registry is not described as a randomized comparison; its allocation is not stated, and the registry record cautions that the arms are not a like-for-like control comparison. A difference between groups in a nonrandomized setting can reflect differences in patient characteristics, clinical decisions, follow-up, or other factors, in addition to any treatment-related difference. No adjustment approach for such factors is reported in the registry record.

The registry’s stated purpose is to understand care strategies in real-world practice, especially for CRT non-responders. That descriptive purpose can be useful for documenting practice and observed outcomes. It does not establish that a specific care strategy caused an outcome. The record does not report how non-responders were defined for analysis or how particular clinical strategies were selected.

What can uncertainty measures add?

General: a confidence interval pairs an estimate with a range that reflects sampling uncertainty under a specified method. A narrow interval usually indicates greater statistical precision than a wide interval, but neither interval width nor statistical significance resolves bias from nonrandom allocation, incomplete follow-up, or outcome measurement. A p-value, when reported, evaluates the compatibility of data with a specified null hypothesis under the test assumptions; it does not measure the probability that a treatment works or that the null hypothesis is true.

No confidence interval, p-value, or test result for the primary endpoint is reported in the registry record. The record’s analysis count is zero. Consequently, there is no reported inferential result to interpret for the primary count. The absence of a reported test does not establish that there was no change; it means the registry record does not provide a numerical analysis from which to assess the result.

How should event counts be read?

The safety information lists participants at risk and affected for serious and other adverse events, as well as deaths. Such counts can describe what was recorded in the registry. General: event-count interpretation depends on whether the entry counts people with at least one event or total event occurrences, whether participants can contribute to more than one event category, and how long participants were observed. Those details are not reported in the registry record. The counts should therefore be treated as descriptive entries, not as rates or comparative risks.

The serious-event terms are accompanied by percentages in the record. The denominator and method underlying each listed percentage are not described in the registry record from the registry record. Their ranking or size should not be used to infer comparative safety without clear definitions, follow-up information, and an appropriate comparison. The record also does not report an analysis linking any adverse event to the device.

What do planning calculations mean?

General: sample-size planning asks how many participants a future study might need under specified assumptions about the effect to detect, the significance level, allocation, and statistical model. A planning illustration based on an observed effect is not the same as the design justification for the registry, and it is not observed power. The stated planning assumptions for this registry’s illustration include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The illustration distinguishes participants per arm for 80% power from total events for time-to-event outcomes.

Those assumptions describe a planning exercise, not a randomized design actually used by this registry. The registry record does not report its own sample-size justification. In particular, the presence of planning assumptions cannot establish that the registry enrolled a number chosen to detect a prespecified effect or that its descriptive outcomes have a particular power. Sample-size illustrations should be read as hypothetical planning aids, not as evidence about the certainty of the observed findings.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Site CRT Responders", "Site CRT Non-Responders")
n      <- c(559, 90)
events <- c(93, 34)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Site CRT Responders  559  93  16.6  13.6  20.0  13.8  19.9  13.8  20.0
ARM  Site CRT Non-Responders  90  34  37.8  27.8  48.6  28.5  48.1  28.4  48.1

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or statistical tests are examined. General: testing many hypotheses can increase the chance of at least one apparently notable result under a situation where none of the tested effects is real. Statistical plans may address this through a prespecified hierarchy, adjustment, or a clear distinction between primary and exploratory analyses. The registry record identifies a primary outcome and lists four outcome measures, but it does not report a multiplicity strategy, a hierarchy for testing, or results of analyses. The listed analysis count is zero, so no multiplicity-adjusted or unadjusted tests are available to interpret.

The primary outcome uses only participants with evaluable data at both six and 12 months. The record states that this population is smaller than the group that completed the two visits, but does not report the number analyzed, the number missing data, reasons for missingness, or how missing measurements were handled. It is therefore not possible to assess whether missingness might have affected the reported outcome count. General: complete-case summaries describe participants with observed data; their relevance to a broader enrolled population depends partly on why other participants lack measurements.

The safety counts use 1524 participants at risk in the serious and other adverse-event entries, while overall enrollment is 1529. The registry record does not explain the difference between these recorded populations. The counts should not be combined or treated as if all outcomes used the same analysis population. It also does not report the timing of safety follow-up, handling of incomplete safety information, or whether affected participants could appear in multiple event categories.

The analysis population definitions for the remaining outcome measures and any missing-data methods are not reported in the registry record. No assumptions about imputation, censoring, interim analyses, or adjusted analyses can be made from the available information.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute chf (4.6%), lead dislodgement or migration (2.7%), other general (2.4%), myocardial infarction (1.2%), other infections (0.9%).

For the CRT Patients group, the record lists 1524 participants at risk for serious adverse events and 226 affected. It also lists 1524 at risk for other adverse events and 403 affected. Deaths are reported as 132. These figures are descriptive safety entries, not estimates from a randomized comparison. The registry record does not report a control group suitable for comparing these counts or an analysis that attributes events to the device.

The serious-event terms listed include Acute CHF at 4.6%, LEAD DISLODGEMENT OR MIGRATION at 2.7%, OTHER General at 2.4%, MYOCARDIAL INFARCTION at 1.2%, OTHER Infections at 0.9%, and Atrial Arrythmia at 0.8%. The registry record does not explain the denominator or calculation method for these percentages. It also does not report the event-specific follow-up period, whether entries represent people or event occurrences, or whether one participant could contribute to multiple terms.

General: adverse-event counts describe events recorded during a study or registry and do not, by themselves, establish causation. Interpretation depends on event definitions, duration of observation, completeness of reporting, and a relevant comparison. Those details are not reported in the registry record. The listed counts and terms should therefore be read as descriptive information rather than comparative safety estimates.

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

The registry record defines a primary outcome that captures improvement of at least one NYHA class between six and 12 months among participants with evaluable data at both time points. That definition identifies what the registry intended to count. The record does not report the number who improved or the size of the primary analysis population, so it does not support a numerical statement about the observed improvement or its precision.

The result, if considered as a count, would describe the participants who met the outcome definition in the evaluable group. It would not automatically describe every enrolled participant, because the primary analysis excludes those without evaluable measurements at both time points. The registry record says that fewer participants were analyzable than completed both visits, but does not provide further details about missing data or the reasons for it.

The registry’s descriptive design also limits conclusions about cause and comparison. Allocation is not stated, the record does not describe a randomized comparison, and the arms are not a like-for-like control comparison. Therefore, the registry entries cannot establish that CRT or any particular clinical-care strategy caused an observed change in NYHA class. They cannot establish comparative effectiveness against an alternative treatment or no treatment.

The adverse-event counts and listed serious-event terms describe what the registry records, but they do not establish that the device caused an event, nor do they give a controlled comparison of safety. The record does not provide enough detail about event timing, denominators for the term-specific percentages, or overlap between categories to treat those entries as comparative risks.

These limitations do not erase the registry’s descriptive purpose. A real-world registry can record clinical outcomes and care patterns in a patient population. In this case, however, the available record does not provide the primary outcome result, detailed analyses, or the methods needed to quantify uncertainty and address possible differences among participants. The appropriate interpretation is therefore bounded: the endpoint and registry aims are described, and safety counts are listed, but comparative or causal conclusions are not supported by the reported information.

14. Why This Trial Matters Statistically

This registry is statistically relevant because it focuses on outcomes and care strategies in real-world CRT practice, including patients described as non-responders. Such settings raise questions that differ from those in randomized trials: clinicians make care decisions in context, patient groups may not be comparable, and observed changes may reflect several influences. The registry’s descriptive aim can document practice, but the design details reported do not support treating its groups as randomized alternatives.

The primary outcome also illustrates why an endpoint definition and an endpoint result are distinct. The registry specifies a threshold for improvement—at least one NYHA class between six and 12 months—and specifies that only participants with evaluable data at both visits are included. Yet the outcome count and the analysis denominator are not reported in the registry record. Without them, readers cannot assess the observed frequency, precision, or representativeness of the primary result.

Safety reporting presents another important statistical issue. Counts, affected participants, event terms, and percentages each need clear definitions and denominators for sound interpretation. The record supplies several counts and terms, but does not describe all the information needed to evaluate their timing, overlap, or comparison. This is a reminder that descriptive safety data should not be converted into causal or comparative claims without an appropriate design and analysis.

Finally, the registry record lists four outcome measures and zero analyses. Registration and completion status do not substitute for reporting estimates and uncertainty. A careful statistical reading distinguishes stated aims and definitions from results that are not reported. The record’s value lies in documenting the registry’s scope and selected measures, while its limitations show why design, analysis populations, missing data, and transparent reporting are essential to interpreting clinical evidence.

15. Limitations

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

Several limitations are specific to the information recorded for this registry. First, the primary endpoint’s numerical result is not reported in the registry record. The number of participants with evaluable NYHA class data at both time points is also not stated, even though the record notes that this analysis population is smaller than the group that completed both visits. Consequently, neither the primary count nor its precision can be assessed.

Second, the registry does not provide a randomized, like-for-like control comparison. Allocation is not stated, and the available arm information describes CRT patients rather than a clearly comparable control group. The registry’s focus on real-world care strategies is consistent with descriptive goals, but it limits causal interpretation of changes in NYHA class and of adverse events.

Third, the record does not define how non-responders were identified for analysis, describe which care strategies were used for them, or report how those strategies were chosen. It also does not report the statistical analysis plan, an analysis for the primary endpoint, confidence intervals, or the handling of missing measurements. Reasons for unevaluable data are not reported in the registry record.

Fourth, safety information is incomplete for detailed comparative interpretation. The at-risk counts and affected counts are listed, as are deaths and selected serious-event terms with percentages. However, the registry record does not explain the denominator for each term-specific percentage, event timing, possible overlap among categories, or whether entries count participants or events. No causal attribution or comparative safety analysis is reported.

Finally, although the record lists four outcome measures, the number of analyses is zero. It does not report multiplicity procedures, interim analyses, or a sample-size justification. These omissions mean that the descriptive details available do not provide a basis for assessing the registry’s statistical power, analysis choices, or the robustness of a treatment-effect claim.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Advance Cardiac Resynchronization Therapy (CRT) Registry — NCT01805154.
• Registry record last updated 2019-08-12; status last verified 2019-07.
• Results first posted 2019-08-12.
• 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.

19. Record Summary

NCT01805154, the Advance Cardiac Resynchronization Therapy (CRT) Registry, is listed as completed and sponsored by Abbott Medical Devices. The registry enrolled 1529 participants with heart failure who had received a market-approved St Jude Medical CRT-D or CRT-P device. Its stated purpose was to understand real-world CRT care strategies, particularly for non-responders.

The primary outcome counts participants with at least one NYHA class of improvement between six and 12 months. Only participants with evaluable data at both visits were included, and the analysis population was smaller than the group that completed both visits. The number analyzed and the primary outcome count are not reported in the registry record. Four outcome measures and zero analyses are listed.

The record reports serious adverse events for 1524 participants at risk, with 226 affected; other adverse events for 1524 at risk, with 403 affected; and 132 deaths. It lists selected serious-event terms with percentages. Allocation is not stated, and the registry does not offer a like-for-like control comparison. The record supports descriptive interpretation, not a causal or comparative estimate.