Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients (NCT01648205), a non-randomized phase 2 study. The primary outcome is Change in QTc Duration at 2 Months.

2. Clinical Question

The study’s stated purpose was to assess whether late sodium channel blockade might shorten the QTc interval across various LQT3 mutations and be considered a safe therapeutic option. That purpose describes the research question; it is not evidence that the treatment did or did not produce a particular change. The registry record gives the outcome definition and comparison periods, but does not give the estimated changes, their variability, or an inferential result.

The schedule matters for interpreting the question. The placebo period comes before the ranolazine period, so the comparison is between different periods in the same stated sequence, not between groups assigned at random to concurrent treatments. Changes over time or differences in the circumstances of the periods could therefore complicate interpretation of a treatment contrast. Whether the analysis addressed such issues is not reported in the registry record.

The registry describes a phase 2, double-masked, sequential, non-randomized study with enrollment of 25. Those design labels do not substitute for the missing outcome estimate. The record also lists a secondary outcome, change in QTc at 6 Months, but its numerical result is not reported in the registry record.

3. Trial Design

The registry identifies this as a phase 2 study with non-randomized allocation, double masking, and a sequential model. It lists enrollment of 25 and the condition Long QT Syndrome. The sponsor is the University of Rochester. The listed interventions are placebo and ranolazine.

The arm description specifies placebo for 1 month followed by ranolazine for 5 months. This gives the intended order and duration of the stated treatment periods, but does not establish that the periods are interchangeable or that they provide a randomized like-for-like comparison. The registry itself flags that the allocation is non-randomized and the arms are not a like-for-like control comparison. A before-and-after sequence can be affected by changes over time as well as by the intervention; whether those possibilities were addressed analytically is not reported in the registry record.

Double masking is a design label in the record. The details of who was masked, how masking was maintained, and whether it remained successful are not reported in the registry record. The process used to allocate participants, the handling of treatment adherence, and any treatment changes are also not reported in the registry record.

The listed study start is 2012-09, primary completion is 2018-07-20, and status is COMPLETED. These registry entries describe the study’s administrative timeline and status, not its treatment effect. The primary endpoint is titled “Change in QTc Duration at 2 Months,” with a timeframe of 1 month to 2 months. The description compares change at 2 months on ranolazine with change at 1 month on placebo and identifies the outcome as prespecified.

Although the registry records outcome and design metadata, the numerical primary result and the analysis plan are not reported in the registry record. In particular, the statistical model, adjustment variables, and analysis population are not reported in the registry record. The label “sequential” alone does not establish how within-person or period effects were modeled.

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.

Placebo

Reasons for not completing this period:

Ranolazine

Reasons for not completing this period:

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 Change in QTc Duration at 2 Months, measured over 1 month to 2 months.

The primary endpoint is change in QTc duration, a continuous measure of the corrected QT interval. The registry gives the unit as “miliseconds,” identifies the summary parameter as a mean, and describes dispersion using a standard deviation. The timeframe is 1 month to 2 months. Its description compares QTc change at 2 months on ranolazine with QTc change at 1 month on placebo and states that the outcome was prespecified.

In general, a change endpoint expresses how a measurement differs between designated assessment times. A mean summarizes the average change in the analyzed observations; a standard deviation describes how spread out individual observations are around that mean. The mean alone does not show how variable the observations were, and the standard deviation is not a measure of the precision of the mean. Precision depends on further information, including the number of observations contributing to the estimate and the analysis used.

QTc is used in this study because the stated research purpose concerns whether late sodium channel blockade might shorten the QTc interval in LQT3. The endpoint therefore corresponds to the physiological question recorded by the investigators. However, the numerical mean change, standard deviation, comparison estimate, and uncertainty around that comparison are not reported in the registry record. The endpoint definition explains what was intended to be measured, but by itself does not establish the direction, size, or precision of any observed effect.

The registry also lists change in QTc at 6 Months as a secondary outcome. Its detailed numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a continuous measure summarized by a mean and standard deviation. It does not report the statistical analysis method used for that endpoint. The explanations below are general statistical guidance, not a description of an analysis confirmed to have been used in this trial.

What does a mean change describe?

In general, a mean change is the average of the individual changes included in an analysis. It provides a measure of the central tendency of observed change, but it does not describe every participant’s response. A mean can be influenced by unusually large or small observations, and different patterns of individual changes can produce the same mean. The standard deviation describes spread among observations; it does not, by itself, quantify uncertainty in the estimated mean or comparison.

For a treatment-period comparison, it is important to know exactly what is being contrasted. This registry’s endpoint description compares change at 2 months on ranolazine with change at 1 month on placebo. The record does not give the numerical change values or the precise statistical contrast calculated from them. It also does not report whether the analysis used paired observations, a model for repeated measurements, or another method. The sequential schedule makes that distinction relevant, because methods can make different assumptions about the relationship between observations collected at different times.

Why does design affect interpretation?

In general, random allocation helps balance measured and unmeasured prognostic factors between treatment groups, on average. This trial is listed as non-randomized, and its stated sequence places placebo before ranolazine. Thus the contrast is not a randomized comparison of concurrent groups. Time, order, changes in participants’ circumstances, and treatment-period effects are potential interpretive considerations in a sequential design. Their presence or effect in this study is not established by the registry record, and methods for addressing them are not reported in the registry record.

Masking is listed as double, but that label does not explain the masking procedures or identify which parties were masked. It also does not show whether masking was maintained. Those details are not reported in the registry record. The model is listed as sequential; the word alone does not specify the statistical structure used to analyze repeated measurements.

How should uncertainty be understood?

In general, a confidence interval communicates uncertainty around an estimated quantity under a statistical method and its assumptions. A narrower interval indicates greater precision than a wider interval, while an interval’s location indicates which values are compatible with the data under that method. It is not a guarantee that the true value lies within the interval. For this endpoint, the confidence interval is not reported in the registry record.

A p-value is, in general, calculated relative to a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not quantify clinical importance. Interpretation depends on the analysis plan, assumptions, and reporting context. The primary-outcome p-value and the details of any hypothesis test are not reported in the registry record. Therefore, the endpoint description cannot be used to infer statistical significance.

The standard deviation and the standard error serve different purposes. In general, the standard deviation describes variation among measured values, while the standard error describes the estimated sampling variability of a statistic. A confidence interval is commonly constructed using an estimate and a measure of its uncertainty, but the method depends on the model and data. The registry specifies standard deviation as the dispersion measure, but does not report the observed value or a standard error for the treatment comparison.

What do the planning assumptions mean?

The registry’s planning illustration is described as being computed from the observed effect, rather than from the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event tables, the stated quantity is total events using the Schoenfeld method; for other outcomes, it is participants per arm.

These are planning assumptions, not evidence about the study’s observed power. A planning calculation asks what sample size would be needed under specified assumptions; it does not show the probability that the completed study detected an effect. The record does not give the numerical observed effect or the planning values in the registry record for this analysis, so no planning estimate can be interpreted. Such illustrations should not be confused with the actual enrollment of 25 or with an outcome estimate.

In general, planning based on an observed effect can be sensitive to uncertainty in that effect. If an observed estimate is imprecise, treating it as a fixed target can make planning conclusions unstable. Sample-size planning also depends on assumptions about variability, significance level, allocation, and analysis method. The registry’s illustration states some assumptions, but the trial’s original sample-size justification is not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a model assumes. It can make standard errors too small and intervals too narrow if the model does not account for the extra variability. This is a general consideration for statistical modeling, not a claim that over-dispersion occurred in this trial. The primary measure is continuous, and the registry gives standard deviation as its dispersion summary; it does not report an over-dispersion assessment or a model that would make such an assessment relevant.

More broadly, a sound interpretation requires the estimate, its uncertainty, the analysis population, and the model assumptions. The registry record identifies the endpoint and design but does not report the primary numerical estimate or enough analysis detail to evaluate those components. Any numerical inferential conclusion would therefore go beyond what the registry record reports.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Placebo", "Ranolazine at 2 Months")
n   <- c(25, 23)
m   <- c(503, 497)
sp  <- c(46, 47)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Placebo  25  503.000  46.000  484.012  521.988
CARM  Ranolazine at 2 Months  23  497.000  47.000  476.676  517.324

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome, change in QTc duration at 2 Months, and a secondary outcome, change in QTc at 6 Months. It also records 2 outcome measures and 2 analyses. The numerical outcomes and the relationship between the listed analyses are not reported in the registry record. The registry does not report whether the analyses correspond one-to-one with the outcomes or whether additional comparisons were made.

In general, multiplicity arises when several hypotheses or outcomes are assessed. Repeated testing can increase the chance of at least one result appearing unusual under a collection of null hypotheses. Statistical plans may address this by identifying a primary endpoint, defining a testing sequence, or adjusting significance thresholds or intervals. The use of any multiplicity procedure, the intended testing hierarchy, and the rationale for it are not reported in the registry record. The fact that the primary outcome is described as prespecified does not reveal whether secondary analyses were adjusted or how they were interpreted.

Missing-data methods are also not reported in the registry record. The record does not describe the extent or pattern of missing QTc measurements, whether participants discontinued or missed visits, or how incomplete outcome data were handled. It does not state whether the analysis used all observed measurements, a particular imputation method, or a complete-case approach. These omissions prevent assessment of whether the analyzed observations may differ from the enrolled population.

The analysis population is not reported in the registry record. In general, an analysis-population definition clarifies who contributes to an estimate and how protocol deviations or treatment exposure are handled. Without that definition and the number contributing outcome data, enrollment of 25 cannot be assumed to equal the number analyzed. The registry also does not report whether the primary analysis was adjusted, the covariates considered, or a sensitivity analysis for missing data or design assumptions. These are unknowns rather than evidence that any particular method was or was not used.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ventricular fibrillation (8.0%).

The registry reports serious adverse event counts by listed group. For ranolazine, 25 participants were at risk and 2 were affected; for placebo, 25 were at risk and 0 were affected. It lists other adverse events affecting 3 participants in the ranolazine group and 0 in the placebo group, with 25 at risk in each group. Deaths are listed as 1 for ranolazine and 0 for placebo. These are descriptive entries in the registry record.

Ventricular Fibrillation is listed among the top serious terms with 8.0%. The record does not provide further detail in the registry record for this analysis about event timing, recurrence, severity beyond the serious classification, or the relationship of that term to the affected-participant count. The event-level details and attribution assessments are not reported in the registry record.

These counts should not be read as proof that a treatment caused an event or as a reliable estimate of comparative risk. Allocation was non-randomized, and the listed schedule was sequential rather than a concurrent randomized comparison. The record does not report whether events were judged related to treatment, nor does it provide a detailed safety-analysis method. Small descriptive counts and the design context warrant restraint in making comparative claims. The registry entries describe what was recorded; they do not establish causality or replace the missing primary efficacy result.

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

The record establishes that investigators planned to study ranolazine in LQT3 patients and to assess change in QTc duration. It identifies the primary comparison as change at 2 months on ranolazine versus change at 1 month on placebo, and labels that outcome prespecified. It also gives a sequential treatment schedule, design labels, and selected safety counts. These details clarify the research question and the structure of the study.

The record does not report the numerical primary outcome. Consequently, it does not show whether QTc change was in a particular direction, how large the mean change was, how variable the observations were, or how precise the comparison was. It also does not report the primary comparison’s confidence interval or p-value. No conclusion about statistical significance or effect magnitude can be drawn from the information recorded about the endpoint alone.

The registry’s stated purpose refers to whether late sodium channel blockade might shorten QTc and be considered a safe therapeutic option. That statement describes the motivation for the study, not its result. The safety counts are also descriptive and cannot establish that ranolazine caused or prevented an event. The non-randomized, sequential design further means that the placebo and ranolazine periods should not be treated as a randomized, like-for-like comparison.

More generally, evidence about an effect depends on the estimate, uncertainty, analysis population, outcome completeness, and design. The registry record does not report several of these components. The enrollment figure is not a substitute for the number analyzed, and the planning illustration is not observed power. The record therefore supports a description of the study’s question and design, but not a quantitative judgment about the primary QTc result.

This distinction is not a statement that the study found no effect. It reflects that the primary numerical result is not reported in the registry record. A missing registry result cannot be interpreted as a null result, and it cannot establish that an effect was present. The appropriate statistical reading is limited to what the record documents.

14. Why This Trial Matters Statistically

This study is statistically notable because the treatment periods are sequential and allocation is non-randomized. The registry explicitly cautions that the arms are not a like-for-like control comparison. In general, a treatment contrast is easier to interpret when treatment assignment separates treatment effects from other differences between groups or periods. A fixed sequence can make treatment and time effects difficult to distinguish, even when masking is used. The analysis methods needed to assess that issue are not reported in the registry record.

The primary endpoint is a continuous change measure, with the mean and standard deviation identified as the intended summaries. That makes the distinction between average change, variability, and precision central to interpretation. The record defines the endpoint but does not report its numerical result. This illustrates why outcome definitions and design descriptions cannot substitute for estimates and uncertainty measures.

The registry also records a secondary QTc outcome and counts two outcome measures and two analyses. Multiple outcomes can raise questions about how results were prioritized and whether inference was adjusted for multiple testing. The record identifies the primary outcome as prespecified, but multiplicity procedures and a testing hierarchy are not reported. Statistical interpretation therefore requires caution beyond simply noting the endpoint labels.

Finally, the record includes planning assumptions but does not report the primary estimate or the numerical planning illustrations in the registry record for this analysis. Planning calculations are not observed power, and assumptions tied to an observed effect are not the same as the trial’s original design justification. The sample-size justification is not reported in the registry record. Together, these features make transparent outcome reporting especially important: readers need the estimate, uncertainty, analysis population, missing-data handling, and model description to judge what the trial’s data support.

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 direct limitation for statistical interpretation is that the registry record does not report the numerical primary outcome. The mean change, standard deviation, treatment-period contrast, confidence interval, and p-value are not reported in the registry record. The secondary outcome’s numerical result is not reported in the registry record either. Therefore, the magnitude, direction, and precision of the QTc findings cannot be assessed from the record.

The design is non-randomized and sequential, with placebo followed by ranolazine. The record warns that the arms are not a like-for-like control comparison. Changes over time, period effects, or other differences between the periods could complicate interpretation in general, but their relevance to this study cannot be determined from the registry entries. The statistical method used to address the sequence is not reported in the registry record.

The analysis population and outcome completeness are not reported in the registry record. Enrollment of 25 does not identify the number with measurements at each visit or the number contributing to each analysis. Missing-data patterns, withdrawal details, adherence, protocol deviations, and sensitivity analyses are not reported in the registry record.

The registry lists double masking, but the parties masked, masking procedures, and success of masking are not reported in the registry record. Covariate adjustment, model assumptions, multiplicity procedures, and the prespecified statistical analysis plan are also not reported in the registry record. The original sample-size justification is not reported in the registry record; the described planning illustration is based on the observed effect and should not be interpreted as observed power.

Finally, the safety entries provide counts but not detailed event narratives, attribution, or timing. These limitations do not show that any specific problem occurred; they identify information not reported in the registry record that would be needed for a fuller assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients — NCT01648205.
• Registry record last updated 2022-04-07; status last verified 2022-03.
• Results first posted 2022-04-07.
• 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

The registry record describes NCT01648205, “Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients,” with the official title “Efficacy of Ranolazine in LQT3 Patients.” It lists phase PHASE2, non-randomized allocation, double masking, a sequential model, enrollment of 25, and status COMPLETED.

The listed schedule is placebo for 1 month followed by ranolazine for 5 months. The prespecified primary outcome is change in QTc duration at 2 Months, comparing change at 2 months on ranolazine with change at 1 month on placebo. Change in QTc at 6 Months is listed as a secondary outcome.

The numerical primary and secondary outcome results are not reported in the registry record. Safety entries include serious adverse events affecting 2 participants in the ranolazine group and 0 in the placebo group, and deaths of 1 and 0, respectively. These descriptive counts should be interpreted in light of the non-randomized sequential design.