Quartet Lead and Resynchronization Therapy Options III (QUARTO_III): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Quartet Lead and Resynchronization Therapy Options III (QUARTO_III) (NCT02476201), a na na study. The primary outcome is Number of CRT Responders.

2. Clinical Question

The clinical question is therefore about response within a treated group, not about whether MPP activation changes response relative to a control. Without a reported responder count, the registry record cannot quantify the observed response level or its precision. The stated endpoint also depends on having a 6-month echocardiographic evaluation; the record says that some subjects were not part of the analysis if they withdrew or did not complete that visit, and its population description ends before fully specifying another exclusion. The complete eligibility and analysis rules for the endpoint are not reported in the registry record.

3. Trial Design

This completed study, NCT02476201, is titled Quartet Lead and Resynchronization Therapy Options III (QUARTO III). Abbott Medical Devices is listed as the sponsor. The record gives a start date of 2016-02 and a primary completion date of 2019-02-13. Enrollment was 105, and the study status is COMPLETED. The condition listed is heart failure.

The design is recorded as single-group, with allocation listed as NA and masking as NONE. The intervention was MPP ON: the MPP feature was activated in all patients. All participants were intended to have a CRT-D device and a Quartet LV quadripolar lead. Because no concurrent comparison group is described, the design can describe outcomes among participants receiving the intervention but cannot isolate a contrast with another pacing approach.

The stated study purpose was to assess at 6 months the percentage of patients meeting the CRT responder definition. The registry outcome is labeled Number of CRT Responders and uses participants as its unit. The response definition is an improvement of >15 % in LVESV, assessed by echocardiography. The reported details do not include an observed count, a percentage, or an estimate of uncertainty for this outcome.

Secondary outcomes include changes in LV echocardiographic parameters, the number of CRT super-responders, hospitalization and mortality rates, and change in NYHA classification. The registry record lists five outcome measures and one analysis, but does not describe the statistical model or detailed analysis plan. It also does not report a phase beyond NA. The single-group structure and absence of a stated comparator are central to interpreting what the study can establish: it can describe outcomes in the enrolled group, but cannot provide a randomized estimate of a treatment difference.

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: The analysis population included subjects implanted with a Quartet LV quadripolar lead and with the MPP feature activated and who had a 6-month CRT response evaluation via echocardiography. 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of CRT Responders, measured over 6 months.

The primary endpoint is the number of participants classified as CRT responders at 6 months after implantation. The registry defines a responder as a patient with an improvement of >15 % in LVESV, measured by echocardiography. LVESV is a left-ventricular measure, and the endpoint uses its change to classify participants rather than reporting a continuous mean change as the primary outcome.

A responder definition turns a measured clinical or physiological change into a binary classification: each evaluated participant either meets the stated criterion or does not. This can make a result easier to describe as a count or proportion, but it also means the result depends on the chosen threshold and on obtaining the required measurement. The record identifies the threshold and assessment method, but does not report the number of participants who met the criterion, the analyzed denominator, or a confidence interval.

The study purpose refers to the percentage of responders, while the registry outcome is specified as a count of participants. A count alone does not establish the percentage unless the relevant denominator is also known. The analysis population was described as participants with an echocardiographic 6-month response evaluation, with some exclusions for missing or incomplete visits. The final analyzed population and the handling of participants without an evaluable assessment are not reported in the registry record. Consequently, the endpoint definition is available, but its observed result and precision are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome, a single-group study, and an analysis population based on evaluation at 6 months. It does not report the statistical methods used to analyze the primary outcome. The following concepts are general explanations of how such outcomes can be interpreted; they should not be read as a description of an unreported protocol.

What does a binary responder outcome represent?

General: A binary endpoint classifies each participant into one of two categories, such as meeting or not meeting a response definition. The responder count is the number meeting the criterion. A responder proportion relates that count to a defined denominator. The denominator must be specified because different populations, such as all enrolled participants or only participants with an evaluable 6-month assessment, can yield different interpretations. In this record, the outcome unit is participants, but the observed count and analysis denominator are not reported in the registry record.

The criterion is an improvement of >15 % in LVESV by echocardiography. A threshold converts a measured change into a category. This is useful for a responder-rate question, but it discards information about how far a participant's change lies above or below the cutoff. A continuous analysis of change could retain more detail, but the primary outcome described in the record is a participant count, not a reported continuous estimate. The registry does list changes in LV echocardiographic parameters as a secondary outcome, without reporting its numerical results or analysis method.

How should precision be understood?

General: An estimate from a sample is subject to sampling variability. A confidence interval expresses a range of values compatible with the observed data under a statistical method and its assumptions. Wider intervals indicate less precision than narrower intervals. The registry record does not report a confidence interval or the primary observed estimate, so neither the location nor the precision of the response result can be assessed.

A p-value addresses compatibility between data and a statistical null model; it does not state the probability that a treatment works, and it does not describe the size of an effect. The registry entries do not report a primary p-value, a null hypothesis, or a statistical test. Statistical significance should not be inferred from the study status or from the existence of a defined outcome.

What does the single-group structure allow?

General: A single-group outcome can describe what was observed among participants receiving the study intervention. A treatment effect, by contrast, is a difference between outcomes under alternative treatment conditions. A comparison group helps estimate such a contrast, while random assignment can help balance known and unknown factors on average. This study is listed as single-group, with allocation NA and masking NONE, and no comparator is reported. Thus, even if a response result were available, it would not be a randomized comparison of MPP ON against another strategy.

This distinction does not make a single-group description meaningless. It means the interpretation is narrower: it concerns the observed group and cannot separate intervention effects from natural change, background care, or other influences. The registry does not report a causal analysis designed to address those issues.

What do the planning illustrations mean?

General: A sample-size calculation asks how many participants a future or planned comparison might require under stated assumptions. It is not an observed result and is not evidence that a study had a particular probability of detecting an effect. The planning illustration associated with the record uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its target effect is a stated fraction of the observed effect. Those are illustrative calculation assumptions, not a reported justification for this trial's enrollment of 105.

The trial itself is single-group, whereas the planning illustration describes equal allocation between two arms. It should therefore not be mistaken for the design actually used. No trial-specific sample-size justification is reported in the registry record. The illustration is also not observed power: it does not tell whether the study detected an effect, and it does not compensate for the missing primary outcome estimate.

What can be said about over-dispersion?

General: Over-dispersion arises when variability in count data is greater than a chosen statistical model expects. A model that ignores extra variability can produce uncertainty estimates that are too small. This consideration may matter for some count outcomes, but the primary endpoint is a count of participants meeting a binary responder definition, and no model or dispersion estimate is reported. The record does not indicate that an over-dispersion adjustment was used or needed.

Overall, the statistical information reported is sufficient to identify the outcome definition, time point, study structure, and intended analysis population in part. It is insufficient to reconstruct the primary estimate, its uncertainty, or the inferential method. Those details are not reported in the registry record.

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("MPP ON")
n      <- c(79)
events <- c(53)
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  MPP ON  79  53  67.1  55.6  77.3  56.1  76.4  56.1  76.4

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies five outcome measures and one analysis. The primary outcome is the number of CRT responders at 6 months. The listed secondary outcomes concern changes in LV echocardiographic parameters, CRT super-responders, hospitalization and mortality, and NYHA classification. Their numerical results and the analyses used for them are not reported in the registry record.

When a study evaluates several outcomes or makes several statistical comparisons, the chance of at least one apparently unusual result can increase. General methods for addressing this include prespecifying a primary endpoint, adjusting for multiple comparisons, or treating secondary findings as exploratory. The registry record does not report whether any multiplicity adjustment was planned or applied, how outcomes were prioritized beyond identifying the primary outcome, or whether analyses were prespecified. No adjustment should be assumed.

The primary analysis population was described as subjects implanted with the Quartet LV quadripolar lead, with MPP activated, and with a 6-month CRT response evaluation by echocardiography. The description identifies withdrawal before the 6-month visit and failure to complete that visit as exclusions. The remaining population text is incomplete, so the full exclusion rule is not reported in the registry record. The number excluded and the number actually analyzed are also not reported.

Missing-data handling is important because participants without a 6-month assessment may not have the same outcomes as those who were evaluated. General approaches can include analyzing evaluable cases, imputing missing outcomes, or conducting sensitivity analyses under different assumptions. The registry record does not state which approach was used, whether any measurements were missing or unusable, or whether sensitivity analyses were performed. It also does not report how missing secondary outcome measurements were handled. Consequently, the representativeness of the evaluated population and the robustness of the primary result cannot be assessed from the registry record.

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: lead dislodgment (3.8%), atrial arrhytmia (1.9%), coronary artery disease (1.0%), encephalopathy (1.0%), exacerbation of heart failure (1.0%).

The safety information lists a total enrolled group of 105 participants. It records 16 participants affected by serious adverse events, 11 affected by other adverse events, and 2 deaths. These are distinct registry figures and should be read as recorded counts, not as a comparison between groups: the study has no comparator group. The registry record does not report an assessment attributing these events to MPP or to the implanted device.

The most frequent serious adverse event terms listed are Lead dislodgment at 3.8%, Atrial Arrhytmia at 1.9%, and Coronary Artery Disease, Encephalopathy, Exacerbation of Heart Failure, and Trauma at 1.0% each. The registry record does not provide additional detail on timing, severity beyond the serious-event classification, event resolution, or whether a participant could contribute more than one event term. These percentages should not be interpreted as treatment-attributable risks without information about attribution and the method used to calculate them.

Safety counts summarize what was recorded in this enrolled group. In a single-group study, they do not establish how event frequency compares with another treatment or with an untreated condition. The record does not report the relevant comparison or causal assessment, so the listed figures are descriptive.

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

The record establishes that QUARTO III was a completed study of MPP activated in patients implanted with a CRT-D device and a Quartet LV quadripolar lead. Its primary question concerned CRT response at 6 months, with response defined as an improvement of >15 % in LVESV measured by echocardiography. It also records enrollment of 105 participants and lists secondary outcomes and safety counts.

The record does not report the observed number or percentage of CRT responders, the analyzed denominator, or a confidence interval. It therefore does not establish how frequently participants met the response definition or how precise that estimate was. The listed enrollment count cannot be substituted for the endpoint denominator because the analysis population required a 6-month echocardiographic evaluation and included stated exclusions.

Even if a responder result were available, the single-group design would limit what it could mean. A response frequency among participants with MPP ON would describe the observed group; it would not show the difference that would have occurred under another pacing strategy. There is no comparator or randomized allocation reported, and the registry does not describe an adjustment intended to estimate a comparative treatment effect. The study structure therefore does not support attributing any within-group change solely to MPP activation.

The safety figures are likewise descriptive. They list affected participants and deaths in the enrolled group, along with serious event terms and percentages, but do not supply a comparison or event-attribution results. Secondary outcomes are identified, but their findings are not reported in the registry record. In short, the record describes what the study set out to evaluate and how some outcomes were defined, but it does not supply enough outcome results to determine the observed response magnitude, its uncertainty, or a comparative effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly stated research question and a quantitatively interpretable result. Its primary endpoint is defined by a thresholded echocardiographic measure at a specified follow-up time, and its intended analysis population is linked to completion of that assessment. Those details clarify what would count as a response and which participants were intended to contribute to the primary analysis.

The study structure is equally important. With a single group and no comparator, the central estimand is descriptive: the frequency of response among evaluated participants. This differs from a treatment contrast, which asks how outcomes differ between alternative strategies. Keeping that distinction clear prevents a within-group outcome from being misread as evidence of comparative benefit or harm.

The record also illustrates why an outcome definition alone is not enough for statistical interpretation. A responder threshold does not reveal how many participants met it, how many were assessed, or how uncertain the resulting estimate is. Without those results, readers cannot assess the scale or precision of the observed response. Missingness matters because the primary population depended on a completed echocardiographic evaluation, while the final denominator and handling of unavailable assessments are not reported.

Finally, the presence of multiple secondary outcome domains raises questions about prioritization and multiplicity, but the registry does not report the relevant analysis plan. These are not reasons to infer a particular analysis; they are reminders that interpreting a trial requires both outcome values and transparent methods. Here, the design and endpoint are described, while the primary numerical finding and key analysis details remain unreported in the registry record.

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.

The most immediate limitation for statistical interpretation is that the primary responder result is not reported in the registry record. No observed count, percentage, analysis denominator, or uncertainty interval is available. As a result, the planned primary question cannot be answered quantitatively from the record.

The single-group design is a further limitation for causal interpretation. The registry reports no comparator and lists allocation as NA. Outcomes in participants receiving MPP ON cannot, from this design alone, establish how outcomes would differ under another pacing approach. Masking is recorded as NONE, and the record does not describe other design features that might address measurement or expectation effects.

The primary population depends on having a 6-month echocardiographic assessment. The record identifies withdrawal and non-completion of that visit as exclusions, but its population description is incomplete. It does not state the number excluded, the final number analyzed, or how missing or unsuitable echocardiographic measurements were handled. This prevents assessment of potential selection effects from unavailable follow-up.

The registry lists secondary outcome domains and five outcome measures, but their results and statistical methods are not reported. It does not describe multiplicity control, interim analyses, or a trial-specific sample-size justification. The available planning illustration is not a report of the trial's own design justification or observed power. Safety information is descriptive and lacks a reported comparator or event-attribution assessment. These gaps limit evaluation of the outcome estimates, their robustness, and their comparative meaning; they do not establish that any unreported method was or was not used.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Quartet Lead and Resynchronization Therapy Options III (QUARTO_III) — NCT02476201.
• Registry record last updated 2022-03-02; status last verified 2022-02.
• Results first posted 2020-08-03.
• 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

NCT02476201, Quartet Lead and Resynchronization Therapy Options III (QUARTO III), is recorded as a completed single-group study sponsored by Abbott Medical Devices. The condition is heart failure, enrollment is 105, and the intervention is MPP ON in patients implanted with a CRT-D device and a Quartet LV quadripolar lead. The record gives a start date of 2016-02 and a primary completion date of 2019-02-13.

The primary outcome is the number of CRT responders at 6 months, defined by an improvement of >15 % in LVESV on echocardiography. The observed responder count, percentage, analyzed denominator, and precision estimate are not reported in the registry record. Secondary outcomes include echocardiographic changes, super-response, hospitalization and mortality, and NYHA classification; their results are not reported.

The study has no comparator listed, and allocation is NA. Safety figures include 16 participants with serious adverse events, 11 with other adverse events, and 2 deaths among the total enrolled group. The registry record does not report comparative or causal attribution for these figures.