Dual Site Left Ventricular (LV) Pacing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dual Site Left Ventricular (LV) Pacing (NCT00944125), a randomized na study. The primary outcome is Change in Left Ventricular End Systolic Volume (LVESV).

2. Clinical Question

The trial also listed broader aims involving heart function, heart-failure-related hospital and clinic visits, symptoms, and uncoordinated contractions. The registry record posts one outcome measure, the change in LVESV. It does not post secondary outcome results for those other aims. Accordingly, the principal statistical interpretation is limited to the posted LVESV summaries and their reported comparison, rather than to every question mentioned in the study summary.

3. Trial Design

This was a prospective, randomized, double-blind crossover study of patients meeting a CRT-D indication. The registered model is crossover, and the interventions were dual-site LV pacing and BiV pacing. In a crossover design, each participant can contribute information under alternate interventions, allowing comparisons to be made within participants. The registry description specifies that the baseline for the second phase was the end of phase one, rather than the baseline measured at randomization. It therefore frames the outcome as the incremental or decremental change during the alternate pacing configuration.

The registry lists planned enrollment of 50 and reports the study as terminated. The start is recorded as 2009-06, and primary completion as 2013-07. The posted primary outcome timeframe is “At 6 months to one year.” These details describe the registered study record; the reason for termination is not reported in the registry record.

The primary outcome analysis lists 17 participants in the dual-site LV pacing group and 14 in the BiV pacing group. The registry describes the analysis population as based on the two randomized groups per protocol. These posted arm counts do not establish how many participants completed both phases, whether all randomized participants had outcome data, or why the analysis counts differ from planned enrollment. Those details are not reported in the registry record.

The record lists no posted statistical analyses and no secondary outcome measures. It gives no reason for termination, detailed sequence or period information, washout procedures, or statistical plan for accounting for the paired nature of crossover observations. Those omissions limit how fully the design and analysis can be evaluated from the registry record alone.

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: Subjects are consented and randomized before the pacing prodecure. They may have been excluded (considered screen fails) if they end up not having the procedure or being identified as inappropriate once the procedure began. 50 Consented and 41 Randomized.

Baseline to 3 Months

3 to 6 Months

Reasons for not completing this period:

6 Months to Study Completion

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis population was based on the two randomized groups per the protocol.

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: Includes both randomized groups, Group A: Randomized to Dual LV pacing for three months then crossed over to Standard BiV pacing for three months, then programmed at the physician discretion. Group B: Randomized to Standard BiV pacing for three months then crossed over to Dual LV pacing for three months, then programmed to physician discretion.

6. Primary Endpoint

The registry lists the primary outcome as Change in Left Ventricular End Systolic Volume (LVESV), measured over At 6 months to one year.

The primary endpoint is change in left ventricular end-systolic volume (LVESV), measured in ml. LVESV is the volume of blood remaining in the left ventricle at the end of contraction. It is a continuous measure of ventricular size and is used in this study to describe changes in left ventricular function during the pacing phases. The registry identifies the endpoint as a mean with standard deviation.

The endpoint description specifies that change during the single-site and dual-site LV pacing phases was to be compared. For the second crossover phase, the baseline is the end of phase one, not the measurement at randomization. The stated aim is therefore to assess the incremental or decremental change associated with the alternate pacing configuration in each participant. This phase-specific baseline is important: it means the reported endpoint is not simply a comparison of two independent changes from one common starting value.

The posted timeframe is “At 6 months to one year.” The registry does not report a more specific measurement schedule, the exact assessment timing for each participant, or the clinical interpretation assigned to a given magnitude of LVESV change. The endpoint is a surrogate measurement of cardiac structure and function; it is not itself a count of hospital visits, symptoms, or other clinical events. The registry record posts no results for those other aims.

7. Results Posted in the Registry

• BiV Pacing: mean -25.91 versus -28.16 on control; difference 2.25 (95% CI -13.90 to 18.40), standardized effect d = 0.10; z-test p = 0.785.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s LVESV change is expressed in ml, and the registry reports a mean and standard deviation for each pacing group. A mean describes the arithmetic center of observed values. A standard deviation describes how dispersed individual measurements are around that mean. These summaries make the average change and the variability visible, but they do not show the full distribution of observations or the within-person relationship between crossover phases.

What does the mean difference represent?

The reported mean difference is 2.25 ml, calculated as the BiV pacing mean relative to the dual-site LV pacing mean. The arm means are -28.16 ml and -25.91 ml, respectively. A difference near zero would indicate similar average changes in the two reported summaries. The sign identifies the direction of the contrast as defined for the comparison; it does not by itself establish a clinically meaningful advantage. The registry does not give a threshold for clinical importance.

Because this is a crossover trial, observations from the two pacing conditions within the same participant are potentially related. A paired analysis uses that relationship and generally compares each participant’s outcome under one condition with that participant’s outcome under the other. The registry’s endpoint description emphasizes an incremental or decremental effect within each participant and defines the second-phase baseline as the end of phase one. However, the posted outcome summaries are organized by arm, and the record does not report the standard deviation of within-participant differences or enough detail to reconstruct a paired analysis. The exact method used for the posted comparison is not reported in the registry record.

How should the p-value be read?

The unadjusted p-value is 0.785. A p-value measures how incompatible the observed result is with a specified null hypothesis under the assumptions of a statistical procedure. It is not the probability that the null hypothesis is true, and it is not a measure of the size or importance of an effect. The record does not state the detailed test specification or analysis plan. A non-small p-value does not prove there is no difference, particularly when the estimate is imprecise.

What does the interval add?

The reported interval runs from -13.9 to 18.4 ml around the mean difference. A confidence interval is a way of expressing uncertainty about an estimated quantity: it identifies values compatible with the estimate under a particular method and its assumptions. Here, the interval includes zero and values on both sides of zero, so the posted result does not narrowly pin down the direction or size of the mean contrast. The confidence level and the method used to construct this interval are not reported in the registry record.

In general, wider intervals indicate less precision, while narrower intervals indicate more precision, provided the methods and assumptions are appropriate. Precision depends on factors such as the amount of information, variability, design, and analysis. For this trial, the available arm counts are 17 and 14, and the reported standard deviations are 14.62 ml and 27.84 ml. These summaries show that variation differs across the posted groups, but they do not supply the paired variability needed to fully assess the crossover comparison.

Why does crossover structure matter?

In general, a crossover design can control for stable differences between participants because each participant may receive both conditions. Its analysis must also account for the order and timing of conditions, possible period effects, and whether the effect of one condition persists into the next phase. The registry gives the phase-specific baseline rule but does not report sequence-specific results, period-effect analyses, or washout information. It is not possible to determine from the record whether these issues were assessed or how they were handled.

More generally, over-dispersion means that observed variability is greater than a model assumes. When present and ignored, uncertainty can be understated. This is a general statistical consideration rather than a reported feature of this continuous LVESV analysis; the registry does not report an over-dispersion assessment. For a continuous endpoint, the relevant concerns include the distribution of values, the paired differences, and the model’s assumptions.

What can the posted analysis establish?

The posted statistics describe the analyzed participants and the comparison as recorded. They do not establish a causal effect beyond the assumptions of the randomized crossover design and the analysis. The registry reports no analysis population details beyond its statement that the population was based on the two randomized groups per protocol. It does not report missing-data methods, adjustments, sensitivity analyses, or a prespecified statistical analysis plan. Consequently, the precision and robustness of the result cannot be fully evaluated from the registry record.

10. Confidence Intervals and Precision

The reported mean difference is 2.25 ml, and its interval extends from -13.9 to 18.4 ml. The interval is important because the point estimate alone can make an uncertain result seem more definite than it is. The lower endpoint is negative and the upper endpoint is positive, so the compatible values include differences in either numerical direction as well as zero.

The interval is broad, indicating limited precision for the mean contrast. It does not identify a narrow range of plausible values. The posted group summaries also show standard deviations of 14.62 ml for dual-site LV pacing and 27.84 ml for BiV pacing. The available record does not show the standard deviation of paired within-participant differences, which is especially relevant in a crossover design. Without that information and a reported analysis method, the uncertainty calculation cannot be fully checked.

The interval’s confidence level and construction method are not reported in the registry record. It is therefore appropriate to describe it as the reported interval without assigning an unstated confidence level. Its inclusion of zero is consistent with the unadjusted p-value of 0.785, but neither statistic demonstrates equivalence. Equivalence requires a defined margin and an analysis designed to assess whether the effect lies within that margin; no such margin or equivalence analysis is reported.

Precision is also distinct from clinical importance. The registry does not specify what range of LVESV change would be considered important. The interval therefore describes statistical uncertainty in the mean difference, not whether any value within it would matter clinically.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrative calculations based on the observed effect, not the trial’s original design assumptions. The listed values are participants per arm, not total participants or total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The trial’s own sample-size justification and original design assumptions are not reported in the registry record.

The 80% power column gives the planned number of participants per arm under those assumptions for a design with an 80% chance of detecting the specified effect if that effect is present. The 90% power column gives the corresponding number per arm for a design with a 90% chance. These are design-planning quantities, not probabilities that the trial result is correct and not evidence about the chance that the observed result represents a real effect.

At 100% of the observed effect, the illustration lists 1,444 participants per arm for 80% power and 1,932 participants per arm for 90% power. At 75% of the observed effect, the figures are 2,566 and 3,435 participants per arm. At 50% of the observed effect, they are 5,773 and 7,728 participants per arm. The pattern reflects a general statistical principle: smaller effects are harder to distinguish from random variation and require more participants for the same power target.

The curve should be read as a visual representation of how the planning requirement changes as the assumed effect changes; it does not add information about the trial’s observed outcome. These figures are not observed power. They use the observed effect as a planning input, so they are sensitive to uncertainty in that estimate and should not be interpreted as a retrospective score of the trial.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 2.250; pooled standard deviation σ = 21.572.
2. n = 2 × (1.96 + 0.842)² × 21.572² / 2.250² = 1,443.0, rounded up to 1,444 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 2.25                      # observed difference in means
sigma <- 21.5724626509721                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(944125)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,444 (80% power), 1,932 (90% power)
 75% of observed effect: n per arm = 2,566 (80% power), 3,435 (90% power)
 50% of observed effect: n per arm = 5,773 (80% power), 7,728 (90% power)
power.t.test: 1444 
Simulated power at n = 1,444 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no posted secondary outcome measures. The study summary nevertheless describes several broader aims, including left ventricular function, heart-failure-related hospital and clinic visits, symptoms, and uncoordinated heart contractions. Results for those other aims are not reported in the registry record. It also lists zero posted analyses, so the record does not give a detailed analysis plan for the primary outcome.

Multiplicity arises when a study evaluates multiple outcomes, timepoints, comparisons, or analyses. In general, the more statistical tests considered, the greater the chance that at least one appears unusual by chance. A planned strategy may address this through a prespecified primary endpoint or an adjustment approach. The record identifies LVESV change as the primary outcome but does not report a multiplicity adjustment or a plan for the several aims described in the summary. It is not possible to determine whether any such strategy was used.

Missing-data information is also limited. The primary outcome arm counts are 17 for dual-site LV pacing and 14 for BiV pacing, while planned enrollment was 50. The record does not provide participant flow, reasons for missing outcomes, phase-completion counts, or missing-data methods. It does not report whether missingness differed by treatment sequence or phase. No assumption about why data are absent can be made from the record.

The analysis population is described as based on the two randomized groups per protocol. The record does not explain the operational definition of that population, state whether an intention-to-treat analysis was performed, or describe how participants with incomplete crossover data were handled. It also does not report sensitivity analyses comparing alternative populations or missing-data assumptions. These omissions matter because exclusions or incomplete paired outcomes can affect both the estimated difference and its precision.

14. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: heart failure (4.9%), sepsis (4.9%), fall (4.9%), chest pain - cardiac (4.9%), syncope (2.4%).

The registry reports serious adverse events for 41 participants at risk in each pacing group. Three participants were affected in the dual-site LV pacing group, and three were affected in the BiV pacing group. These are participant counts, not counts of every serious event, and the record does not provide a detailed account of event timing or whether an event occurred during one or both crossover phases.

The listed serious-event terms include Heart failure, Sepsis, Fall, and Chest pain - cardiac, each recorded as 4.9%; Syncope and Dyspnea are each recorded as 2.4%. The registry does not specify in this record whether each term’s percentage is organized by treatment group or across the study, so those percentages should not be assigned to a specific arm. The figures should also not be added together: a participant may have more than one event, and the record does not give the overlap between terms.

Deaths are not reported in the registry record. Serious-event definitions, monitoring windows, adjudication procedures, and exposure duration by pacing condition are also not reported. The counts therefore describe the posted safety summary but do not establish comparative risk. The registry additionally lists other adverse events affecting 10 participants at risk in the dual-site group and 3 in the BiV group; event-specific details are not given in the record.

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

The posted primary outcome estimates mean LVESV changes of -28.16 ml with dual-site LV pacing and -25.91 ml with BiV pacing. The estimated mean difference is 2.25 ml, with a reported interval from -13.9 to 18.4 ml. This is a description of the observed analysis and its uncertainty. The interval includes zero and values in both directions, so the result does not precisely establish the direction or size of the mean difference.

The unadjusted p-value is 0.785. It does not provide strong evidence against a null difference under the analysis used, but it should not be treated as proof that the configurations are the same. A finding of no statistically clear difference is not the same as a finding of equivalence. The registry does not report an equivalence margin or a protocol designed to establish equivalence.

The result concerns a continuous measure, not the full range of outcomes described in the study summary. The registry record does not post outcome results for hospital or clinic visits, heart-failure symptoms, or uncoordinated contractions. The LVESV result alone cannot answer those questions. Nor does the record provide a threshold for judging whether a change in LVESV is clinically important.

Several design and reporting details constrain interpretation. The trial is recorded as terminated, but the reason is not reported. The analysis counts are 17 and 14 against planned enrollment of 50; participant flow, missing-data handling, and completion of both crossover phases are not reported. The record also lacks detail on the statistical method used for the crossover comparison. These gaps do not change the posted numbers, but they limit assessment of how representative and robust the analysis may be.

The most defensible reading is therefore a statistically uncertain estimate of the difference in mean LVESV change among the analyzed participants. It should not be extended to unreported outcomes, interpreted as evidence of equivalence, or treated as a definitive assessment of clinical benefit or harm.

16. Why This Trial Matters Statistically

This study illustrates why the design and the analysis need to be read together. In a crossover trial, each participant may contribute outcomes under alternate conditions, and the within-participant comparison can be central to the statistical question. The registry’s endpoint description explicitly defines the second-phase baseline as the end of phase one and frames the goal as an incremental or decremental change. Yet the posted numerical summaries are arm-level means and standard deviations. Without paired-difference summaries or a detailed analysis method, readers cannot fully assess whether the reported comparison reflects the crossover structure as intended.

The result also demonstrates the distinction between an estimate and its precision. The point estimate is 2.25 ml, while the reported interval ranges from -13.9 to 18.4 ml. A single mean difference can look conclusive when read alone; the interval makes clear that the estimate is compatible with a broad range of values. The unadjusted p-value of 0.785 does not resolve that uncertainty or demonstrate equivalence.

Finally, registry completeness affects statistical interpretation. Planned enrollment was 50, the study is marked terminated, and the primary outcome analysis counts are 17 and 14. The record does not explain the termination or report participant flow and missing-data procedures. Those omissions make it difficult to judge how the analyzed participants relate to the randomized cohort. This is a useful example of why transparent reporting of design, analysis populations, paired data, and missingness is essential when evaluating trial results.

17. 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 registry record provides limited detail for evaluating this particular crossover study. Although it identifies the design as randomized, double-blind, and crossover, it does not report the treatment sequence for each participant, period-specific results, washout procedures, or analyses of period or carryover effects. These details can matter when participants receive alternate pacing configurations over time.

The primary outcome description sets the baseline for the second phase at the end of phase one, but the posted summaries do not provide within-participant changes or the variability of paired differences. Arm-level means and standard deviations alone cannot show the correlation between a participant’s outcomes in the two phases. The record also does not describe the statistical model or test used for the posted comparison, so its handling of the paired crossover design cannot be confirmed from the registry record.

The study is marked terminated, but the reason is not reported. Planned enrollment was 50, while the outcome analysis lists 17 participants for dual-site LV pacing and 14 for BiV pacing. The record does not explain this difference, report how many participants completed both phases, or give reasons for missing outcome data. It also does not state whether the analysis included all randomized participants or how incomplete crossover records were treated.

Additional limitations include the absence of a reported clinical-importance threshold for LVESV change, no posted secondary outcome results, and no detailed safety-event timing by phase. The registry does not report the original sample-size justification, an analysis plan, or sensitivity analyses. These gaps restrict conclusions to the posted summaries and prevent a fuller assessment of robustness, generalizability, and the relationship between the primary measurement and the wider aims described for the study.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Dual Site Left Ventricular (LV) Pacing — NCT00944125.
• Registry record last updated 2024-10-21; status last verified 2016-03.
• Results first posted 2016-03-21.
• 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.

21. Record Summary

NCT00944125, “Dual Site Left Ventricular (LV) Pacing,” is registered as a randomized, double-blind crossover study sponsored by Wake Forest University Health Sciences. It enrolled 50 participants according to the registry, began in 2009-06, reached primary completion in 2013-07, and is listed as terminated. The reason for termination is not reported in the registry record.

The primary outcome is change in LVESV in ml at 6 months to one year. The posted means are -28.16 ml for dual-site LV pacing and -25.91 ml for BiV pacing, with a mean difference of 2.25 ml, an interval from -13.9 to 18.4 ml, and an unadjusted p-value of 0.785. The analysis counts are 17 and 14, respectively. The record lists one outcome measure, no posted secondary outcomes, and no posted analyses. The available result is uncertain and should be interpreted in light of the limited crossover-analysis and missing-data details.