Optimized Biventricular Pacing Allograft Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optimized Biventricular Pacing Allograft Recipients (NCT01290822), a randomized phase 1, phase 2 study. The primary outcome is Cardiac Output.

2. Clinical Question

3. Trial Design

The registry describes a Phase 1 and Phase 2 study with randomized allocation, a parallel design, and no masking. Enrollment was 12. The listed conditions were dilated cardiomyopathy and ischemic cardiomyopathy, and the study concerned patients with advanced cardiac failure during cardiac transplantation. Its status is terminated; a reason for termination is not reported in the registry record.

The two listed interventions were BiVP and traditional AAI pacing. The BiVP description says that atrioventricular delay, interventricular delay, and left ventricular pacing site were optimized and their effect on cardiac output assessed. The study summary says BiVP results were compared with traditional AAI pacing at an identical heart rate. The primary-outcome description specifies separate comparisons for the dilated and ischemic cardiomyopathy groups.

The registry calls the design randomized and parallel, but the precise assignment procedure, the way participants were allocated to the pacing approaches, and the timing or sequence of pacing assessments are not reported in the registry record. No masking was used. The primary endpoint timeframe is 13 minutes of testing, performed before cardiopulmonary bypass (CPB) for allograft receipt.

The record lists six outcome measures, including the primary cardiac-output endpoint and secondary measures involving atrial latency, interatrial delay, peak left- and right-ventricular dP/dt, and interventricular synchrony. It reports no analyses for these outcomes. The sponsor is Henry M. Spotnitz. The study started in 2007-01, and primary completion was recorded as 2011-03.

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: Results could not be analyzed due to poor enrollment and lack of data.

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 Cardiac Output, measured over 13 minutes of testing; performed before CPB for allograft receipt.

The primary endpoint was cardiac output. The registry frames it as a comparison of cardiac output during AAI pacing and optimal BiVP, with the dilated and ischemic cardiomyopathy groups considered separately. Cardiac output is a measure of the volume of blood pumped by the heart over time. In general, it can be used to assess the immediate hemodynamic response to a pacing configuration. The registry does not report a unit or a more detailed measurement method.

The listed timeframe was 13 minutes of testing, performed before CPB for allograft receipt. The study summary indicates that pacing was compared at an identical heart rate, which is intended to make the pacing configuration the focus of the comparison rather than a difference in rate. That is a description of the intended comparison, not evidence that a complete comparative dataset was obtained.

The primary-outcome entry explicitly states that results could not be analyzed because of poor enrollment and lack of data. Consequently, the record contains no cardiac-output group estimates, uncertainty intervals, or statistical test results. It is not possible to determine from the registry results how large or precise any difference was, or whether the endpoint data supported a comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the registered design tell readers?

The study is recorded as randomized, parallel, and unmasked. In general, random allocation is intended to reduce systematic differences between comparison groups at the point of assignment. A parallel design generally means that participants are assigned to a study group rather than all participants necessarily receiving each intervention in a crossover sequence. These design labels describe the registered structure; they do not by themselves demonstrate that allocation was implemented as planned or that comparable outcome data were collected.

The registry separately describes comparisons of AAI pacing and optimal BiVP at an identical heart rate, and says the primary endpoint was considered separately for the dilated and ischemic cardiomyopathy groups. The exact assignment procedure and measurement sequence are not reported in the registry record. The specific relationship between the parallel design and the pacing assessments is therefore not fully described.

What would an estimate and confidence interval show?

In general, an estimate expresses the observed contrast between groups, while a confidence interval expresses the uncertainty around that estimate under the statistical method used. A narrow interval would indicate greater precision than a wide interval, assuming the method and data are appropriate. Neither can be interpreted without reported outcome data. The registry provides no cardiac-output estimate or confidence interval, so the size, direction, and precision of the primary comparison are unavailable.

A p-value, in general, summarizes how compatible the observed data are with a specified null hypothesis under a statistical model. It does not measure the size or importance of an effect, and it cannot replace an estimate with an uncertainty interval. No primary-outcome p-value is reported. Since the primary comparison could not be analyzed, there is no registered test result to interpret as evidence for or against a difference.

Why does missing outcome data matter?

When measurements are absent, the analyzed participants may not represent all enrolled participants. The potential impact depends on how much data are missing, why they are missing, and whether the probability of missingness is related to participant characteristics or outcomes. Those details are not reported in the registry record. The record identifies poor enrollment and lack of data as the reason the primary results could not be analyzed, but it does not provide a missing-data assessment or a method for handling missing values.

In general, an analysis population should be defined so readers can tell which randomized participants were included and how exclusions were handled. The registry does not report an intention-to-treat population, a per-protocol population, or another analysis population for the primary endpoint. Nor does it state whether any imputation or sensitivity analysis was planned or performed. No assumptions about those methods can be made from the registration.

What does the study's optimization question involve?

The BiVP intervention description identifies atrioventricular delay, interventricular delay (also called right-left delay in the summary), and left ventricular pacing site as settings to optimize. In general, changing device settings can affect measured cardiac performance, and an optimization study needs a defined rule for selecting settings if its results are to be reproduced. The optimization rule, candidate settings, and selection procedure are not reported in the registry record. The record does not establish which specific settings were selected for any participant.

The summary's reference to an identical heart rate states an intended feature of the AAI-versus-BiVP comparison. In general, holding a factor such as pacing rate constant can help isolate the factor of interest. However, the registry does not give the measurement protocol or confirm how this condition was implemented. It would be inappropriate to treat the intended comparison as a verified feature of a complete analyzed dataset.

What can be said about planning and statistical analysis?

The registry does not report a sample-size justification, a target effect used in planning, or a statistical analysis plan. It also does not report interim analyses, adjustment methods, or model specifications. The registration's zero reported analyses is consistent with the explicit statement that the primary outcome could not be analyzed, but it does not reveal whether any unregistered exploratory work occurred. Such work is not reported in the registry record.

General statistical planning should distinguish the number enrolled from the number needed to estimate an effect with useful precision. A small dataset can yield estimates with substantial uncertainty, but no precision calculation can be drawn from enrollment alone. No outcome variability or observed effect is reported for this study, so no numerical assessment of precision or power is possible from the recorded results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary cardiac-output outcome and secondary outcomes for atrial latency, interatrial delay between the right and left atria, peak LV dP/dt, peak RV dP/dt, and interventricular synchrony. Considering several outcomes can create a multiplicity issue: in general, the more statistical tests conducted, the greater the chance of obtaining a nominally notable result by chance if no adjustment or prespecified hierarchy is used. The registry does not report a multiplicity strategy, an outcome hierarchy beyond identifying cardiac output as primary, or any completed analyses.

Missingness is especially important because the registry says the primary results could not be analyzed owing to poor enrollment and lack of data. The number of participants with usable measurements for each outcome, reasons for missing measurements, and any analysis addressing missingness are not reported in the registry record. There is no reported imputation method or sensitivity analysis. Without these details, readers cannot assess whether missing observations might have affected a comparison.

The analysis populations are also not described. The registry does not state which randomized participants were included in an analysis, how withdrawals or incomplete measurements were handled, or whether an intention-to-treat approach was used. Although enrollment was 12, that figure should not be interpreted as the number analyzed for the primary endpoint or any secondary endpoint. The record reports zero analyses and no outcome estimates.

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 0% reporting threshold.

The registry reports that 12 participants were at risk in the serious-adverse-event summary and that zero were affected by serious adverse events. It also reports 12 at risk for other adverse events and zero affected. These are the counts recorded for the study; they do not describe the types, timing, or duration of adverse-event monitoring.

The deaths field is null, which means a death count is not reported in the registry record. It should not be read as a reported count of zero. No leading serious adverse-event terms are listed. The record does not provide further detail about adverse-event definitions, collection methods, or the completeness of safety reporting. In general, a zero count in a registry summary means no events were recorded in that category for the stated group; it does not establish that no unrecorded events occurred or characterize risk beyond the information recorded.

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

The registry establishes that a randomized, parallel, unmasked study of optimized BiVP and traditional AAI pacing was registered for patients with dilated or ischemic cardiomyopathy undergoing cardiac transplantation. The stated primary question concerned cardiac output, with the two cardiomyopathy groups considered separately. The pacing comparison was described as being made at an identical heart rate, and BiVP optimization included atrioventricular delay, interventricular delay, and left ventricular pacing site.

The registry does not establish the comparative result. It explicitly states that the cardiac-output results could not be analyzed because of poor enrollment and lack of data. No group-level results, effect estimate, confidence interval, or p-value is reported. The record therefore cannot show whether cardiac output was higher, lower, or similar under either pacing approach, or how precise a comparison might have been.

This absence of an estimate should not be described as evidence of no effect or equivalence. A finding of equivalence would require a defined margin and an analysis precise enough to assess whether the uncertainty interval lies within that margin. Neither is reported. Likewise, the lack of a reported statistical test does not imply that a test was nonsignificant; there is no reported test result to interpret.

The record also does not provide analyzed results for the secondary outcomes. It cannot support claims about atrial latency, interatrial delay, ventricular dP/dt, or interventricular synchrony. The registered enrollment is not the same as an analyzed sample size, and the available record does not say how many participants contributed data to any outcome.

The safety summary records zero participants affected by serious adverse events and zero affected by other adverse events among 12 at risk in each category. The death count is not reported. These entries should be read as registry safety counts, not as a complete account of all possible events or a comparison of safety between the pacing approaches.

13. Why This Trial Matters Statistically

This study poses a focused physiological question: whether optimized biventricular pacing, compared with traditional atrial pacing at an identical heart rate, is associated with a different cardiac-output measurement in the setting of cardiac transplantation. It also makes the distinct cardiomyopathy groups part of the stated primary comparison. The intervention description identifies several device settings that could affect the measurement, making the definition and reproducibility of optimization relevant to interpretation.

Statistically, the registry illustrates the difference between a planned comparison and an analyzable result. A randomized design can support a comparative question, but its value for inference depends on collected outcome data and a clearly described analysis. Here, the registry records enrollment of 12 and says the primary results could not be analyzed because of poor enrollment and lack of data. Without an estimated contrast and its uncertainty, the design cannot answer the registered primary question in the posted results.

The record also underscores why enrollment, analysis populations, missing-data handling, and precision are separate issues. Enrollment does not reveal how many participants contributed measurements, and an unavailable estimate cannot be rescued by interpretation of the design labels alone. For readers evaluating this trial statistically, the key conclusion is not a direction of effect but the absence of a reported primary comparison.

The secondary outcomes and safety entries provide additional registry information, but they do not replace the missing primary analysis. The record's value is therefore chiefly descriptive: it documents the intended pacing comparison, the outcome and timing, the design labels, and the limitation that prevented analysis. It offers no numerical efficacy estimate to weigh against uncertainty.

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 primary limitation specific to this study is explicit in the registry: results for cardiac output could not be analyzed because of poor enrollment and lack of data. Although enrollment was 12, the record does not identify the number with usable primary endpoint data or explain the missingness. No outcome estimate or measure of precision is available.

The registry's design labels do not resolve important procedural ambiguities. It describes randomized parallel allocation while also describing a comparison of pacing approaches at an identical heart rate and optimization of BiVP settings. The assignment details, pacing sequence, measurement protocol, and relationship between those features are not reported in the registry record. The optimization procedure for atrioventricular delay, interventricular delay, and left ventricular pacing site is also not specified.

The outcome entry gives a testing duration and setting, but no unit, measurement instrument, or detailed endpoint definition. The analysis plan, sample-size justification, statistical model, analysis populations, multiplicity approach, and methods for missing data are not reported. No secondary outcome analyses are available, despite six listed outcome measures.

The study is marked terminated, but the reason for termination is not reported in the registry record. Safety reporting is limited to the recorded counts; the death field is not reported, and event definitions and monitoring details are absent. These limitations prevent conclusions about comparative efficacy, precision, and the completeness of safety information from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Optimized Biventricular Pacing Allograft Recipients — NCT01290822.
• Registry record last updated 2016-10-06; status last verified 2016-08.
• Results first posted 2016-08-15.
• 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 describes a Phase 1 and Phase 2 randomized, parallel, unmasked study of optimized BiVP compared with traditional AAI pacing in patients with dilated or ischemic cardiomyopathy undergoing cardiac transplantation. Enrollment was 12. The listed primary endpoint was cardiac output, assessed during 13 minutes of testing before CPB for allograft receipt. The primary question concerned separate comparisons for the two cardiomyopathy groups.

The record states that the primary results could not be analyzed because of poor enrollment and lack of data. No primary or secondary outcome analyses are reported. The study status is terminated; the reason is not reported in the registry record. The safety summary lists zero participants affected by serious adverse events and zero affected by other adverse events among 12 at risk in each category; deaths are not reported.