PEGASUS CRT Study: Atrial Support Study in Cardiac Resynchronization Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PEGASUS CRT Study: Atrial Support Study in Cardiac Resynchronization Therapy (NCT00146848), a randomized phase 4 study. The primary outcome is Clinical Composite Score.

2. Clinical Question

This is a question about an overall clinical classification rather than a single measurement. Its categories combine events and assessments that may reflect different aspects of participants’ status. The registry also lists change in quality of life and change in self-assessed physical activity as secondary outcomes, but their results are not reported in the registry record.

3. Trial Design

The PEGASUS CRT Study is recorded as a randomized, single-masked, parallel-group Phase 4 trial. The registry lists an enrollment of 1742 and heart failure as the condition. The sponsor is Boston Scientific Corporation. The recorded study start is 2004-12, primary completion is 2009-01, and status is completed.

The intervention was atrial support pacing through cardiac resynchronization therapy, using devices in the RENEWAL family of CRT-D devices. Participants were assigned to one of three programming strategies. In DDD-40, pacing was limited to situations in which the rate fell below 40 bpm. DDDR-40 used that threshold or initiated atrial support pacing when needed in response to increased activity. DDD-70 delivered atrial support pacing when the rate fell below 70 bpm. The DDD-40 arm is identified as the comparator.

Randomization assigns participants to study groups by chance; in general, this is intended to reduce systematic differences between groups at the point of assignment. A parallel-group design means participants are assigned to a study group rather than being described as cycling through each program. The record does not report the allocation ratio or the details of the randomization procedure. It identifies masking as single, but does not identify which people were masked or explain how masking was maintained.

The primary outcome was assessed from randomization at 6-weeks through the 12-month visit. The registry describes an intention-to-treat analysis, meaning participants were analyzed according to randomized group. It also states that last observation carried forward was used for missing NYHA and Global Assessment measures at 12 months. The registry record does not report the protocol, the sample-size justification, or further details of the statistical analysis plan.

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: All patients with successful system implants were programmed to DDD-40 (atrial rate support above 40 bpm; limited atrial pacing) for the first 6-weeks of the trial. Randomization (1:1:1 allocation) occurred after patients had reached the 6-week visit and continued to meet all of the eligibility criteria for the trial.

Pre-randomization

Reasons for not completing this period:

Post-randomization

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis is intention to treat (ITT) in terms of patient's being analyzed according to their randomized group. Last observation carried forward (LOCF) method was used for missing NYHA and global assessment measures at 12 months.

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 Clinical Composite Score, measured over From randomization (6-weeks) through 12-month visit.

The primary endpoint is the Clinical Composite Score, expressed as a classification of participants as improved, unchanged or worsened. It uses four components: death, heart failure hospitalization, NYHA class and the patient’s Global Assessment rating. The stated timeframe is from randomization at 6-weeks through the 12-month visit. The registry describes improved as the best value and worsened as the worst value.

A composite endpoint brings multiple measures into one overall classification. In general, this can represent several dimensions of clinical status within a single outcome, rather than focusing only on one event or assessment. It can also make the result harder to interpret: a participant’s category reflects a combination of components, and the record’s composite description does not show which component contributed most to a particular classification. The endpoint should therefore be understood as a grouped assessment, not as a direct measure of any one component.

The registry says that missing NYHA and Global Assessment measures at 12 months were handled using last observation carried forward. It does not report the numerical distribution across improved, unchanged and worsened, or an inferential comparison among the pacing groups. The result and its precision are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group comparison with single masking and an intention-to-treat primary analysis. The following statistical concepts are general explanations; the registry record does not report the full analysis plan or the specific tests used.

What does randomization contribute?

In general, randomization uses chance to allocate participants to groups. Its purpose is to reduce systematic differences at the start of a trial, including differences that researchers may not have measured. It does not guarantee that groups will be identical, and it does not replace clear reporting of group outcomes. The record identifies randomization but does not report the allocation procedure or allocation ratio.

What does an intention-to-treat analysis mean?

In general, intention-to-treat analysis compares participants according to their randomized assignment. This preserves the original group comparison and avoids redefining groups based on events after randomization, such as adherence or changes in treatment. The registry explicitly says the primary analysis used this approach. It does not provide further details on how every type of missing or unavailable outcome information was handled.

How should a three-category composite be read?

The Clinical Composite Score classifies participants as improved, unchanged or worsened, based on death, heart failure hospitalization, NYHA class and the patient’s Global Assessment rating. In general, combining components can capture several dimensions of outcome in one summary. However, components may differ in importance, frequency, and the way they are measured. An overall category cannot, by itself, show whether a pattern is mainly associated with one component or reflects several. The registry’s description calls improved the best value and worsened the worst value, but does not report a statistical model for the categories or a component-by-component breakdown.

For categorical outcomes, a statistical comparison may summarize how group distributions differ, but its interpretation depends on the analysis chosen and the outcome data. A confidence interval, when reported, describes uncertainty around an estimate under the assumptions of the method; it is not a guarantee about the true effect. A p-value, when reported, measures how compatible the observed data are with a specified statistical model under a null hypothesis. Neither quantity replaces the group counts and effect estimate needed to judge the scale and precision of a comparison. The registry record does not report these statistics for the primary endpoint.

What does last observation carried forward assume?

The record says last observation carried forward was used for missing NYHA and Global Assessment measures at 12 months. In general, this procedure substitutes a participant’s last observed value for a later missing measurement. It is a way of creating an analysis value, but it relies on an assumption that the carried-forward value is a reasonable representation of the missing value. If health status changes after the last observation, this assumption may not hold. The procedure does not recover the unobserved measurement. The number of missing assessments and sensitivity analyses are not reported in the registry record.

What can adverse-event counts tell us?

Counts of participants with an event are descriptive. Interpreting them comparatively also requires knowing which events are included, how events were collected and classified, the relevant analysis population, and the approach to comparing groups. The record lists affected and at-risk counts under an other adverse-event category, but does not identify event terms or report a comparative analysis. A zero at-risk count in the serious-event fields means those fields do not offer a usable denominator for interpreting serious-event frequency; it should not be read as proof that no events occurred.

General statistical practice also distinguishes a prespecified analysis from a post hoc one, and often considers whether multiple outcomes or comparisons affect interpretation. The registry lists three outcome measures and six analyses, but does not describe multiplicity procedures, an interim-analysis plan, or the statistical test for the primary comparison. Such details are not reported in the registry record, so they should not be inferred from the design label or endpoint description.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the Clinical Composite Score as the primary outcome and lists change in quality of life and change in self-assessed physical activity as secondary outcomes. It reports three outcome measures and six analyses, but does not explain how those analyses relate to particular outcomes or pacing-group comparisons. Any approach to controlling multiplicity, such as adjusting interpretation when several hypotheses are tested, is not reported in the registry record. An interim-analysis plan is also not reported.

For the primary outcome, the record states that the analysis was intention to treat. It further says last observation carried forward was used for missing NYHA and Global Assessment measures at 12 months. The amount and pattern of missing data are not reported in the registry record, nor are sensitivity analyses that might examine whether conclusions depend on the imputation approach. The missing-data handling for the other composite components is not described.

The registry record does not provide the numerical primary-outcome results or inferential statistics. Results for the listed secondary outcomes are not reported in the registry record either. It is therefore not possible to assess from the recorded information whether the primary comparison was statistically significant, how precise an estimated difference was, or whether interpretation was affected by multiple testing or missing information.

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

The record establishes that PEGASUS CRT was a randomized, single-masked, parallel-group Phase 4 trial of three pacing programs in people with heart failure. It describes a primary outcome that combines death, heart failure hospitalization, NYHA class and patient Global Assessment into improved, unchanged or worsened categories. It also states that the primary analysis followed intention-to-treat principles and used last observation carried forward for missing NYHA and Global Assessment measures at 12 months.

Those design and methods details do not disclose the primary outcome result. The registry record does not report the group distributions across the three composite categories, a treatment-effect estimate, a confidence interval or a p-value. It is therefore not possible to determine the observed direction, size or precision of a primary comparison from the recorded information. The record also does not report results for the listed secondary outcomes.

The adverse-event entries offer limited descriptive information. They list affected-participant counts and at-risk counts under an other adverse-event category, without event terms or comparative statistics. Serious-event fields have zero at-risk counts, so they do not support a conclusion about serious-event occurrence.

In general, a trial’s design can help explain how a comparison was intended to work, but design information alone is not evidence of the observed outcome. Likewise, a composite endpoint can summarize several dimensions, yet it does not reveal the contribution of each component without component-level reporting. The posted information does not support claims that one pacing strategy was better, worse or equivalent to another. It also does not establish what would happen in populations or settings beyond those described in the registry record.

12. Why This Trial Matters Statistically

This trial is statistically notable for contrasting three device-programming strategies while defining a primary outcome that combines event-based and assessment-based components. That combination raises an important interpretive issue: an overall classification may be concise, but readers need the category distributions and component results to understand what the comparison represents. Those numerical results are not reported in the registry record.

The record also illustrates why analysis-population and missing-data descriptions matter. It states that the primary analysis was intention to treat, preserving randomized group assignment for analysis, and specifies last observation carried forward for missing NYHA and Global Assessment measures at 12 months. Such details help identify the approach used, while the absence of missingness summaries and sensitivity analyses leaves uncertainty about the robustness of that approach.

Finally, the record distinguishes the existence of adverse-event fields from evidence that can support a safety comparison. Some affected and at-risk counts are listed for the other adverse-event category, while serious-event fields have no at-risk participants recorded. Without event descriptions and analyzable serious-event information, those fields cannot be treated as a full comparative safety analysis. These reporting features make the study useful for discussing what trial design and endpoint definitions can establish—and what outcome reporting is needed before statistical conclusions can be drawn.

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 central limitation for interpreting this trial from the registry record is that the primary endpoint’s group results are not reported. The record defines the composite and analysis population but does not give the counts in the improved, unchanged and worsened categories or a statistical comparison. The direction, magnitude and precision of the primary result therefore cannot be assessed from the recorded information.

The composite includes death, heart failure hospitalization, NYHA class and patient Global Assessment. Results for the individual components are not reported, so the contribution of each component to the overall classification is unknown. Secondary outcome results for quality of life and self-assessed physical activity are also not reported.

The record identifies single masking but does not state who was masked or how masking was maintained. It does not report the randomization procedure or allocation ratio. These omissions limit assessment of how assignment and masking were implemented, without indicating that either was inadequate.

For missing data, the record specifies last observation carried forward for missing NYHA and Global Assessment measures at 12 months, but does not report how much information was missing, its distribution across groups, or sensitivity analyses. It also does not describe missing-data handling for every component of the composite. The statistical analysis plan, any multiplicity procedure and any interim analyses are not reported in the registry record.

Adverse-event entries lack event terms and comparative statistics. The serious-event fields show zero at-risk counts, limiting their interpretation. These reporting gaps constrain statistical interpretation; they do not, by themselves, establish that the trial was poorly conducted or that any pacing strategy had a particular effect.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: PEGASUS CRT Study: Atrial Support Study in Cardiac Resynchronization Therapy — NCT00146848.
• Registry record last updated 2011-12-28; status last verified 2011-12.
• Results first posted 2010-09-23.
• 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

The PEGASUS CRT Study is recorded as a completed, randomized, single-masked, parallel-group Phase 4 trial sponsored by Boston Scientific Corporation. It enrolled 1742 participants with heart failure and compared DDD-40, DDD-70 and DDDR-40 pacing programs using CRT-D devices. The primary outcome was a clinical composite classifying participants as improved, unchanged or worsened based on death, heart failure hospitalization, NYHA class and patient Global Assessment, from randomization at 6-weeks through the 12-month visit.

The primary analysis is described as intention to treat, with last observation carried forward for missing NYHA and Global Assessment measures at 12 months. Numerical primary results and statistical comparisons are not reported in the registry record. Secondary outcome results and further details of multiplicity, allocation and masking are also not reported.