Lorazepam for the Treatment of Status Epilepticus or Repetitive Status Epilepticus in Japan: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lorazepam for the Treatment of Status Epilepticus or Repetitive Status Epilepticus in Japan (NCT02239380), a registered phase 3 study. The primary outcome is Percentage of Participants Who Achieved Seizure Free Interval of At Least 30 Minutes After Initial Dose (Dose 1) of Study Drug.

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase 3 study of intravenous lorazepam in people with status epilepticus or repetitive status epilepticus in Japan. It describes the study as multicenter, open-label, and non-controlled. The listed intervention is lorazepam, and the record does not describe a comparator intervention. Although the design model is classified as parallel, that label does not establish a controlled comparison: the registry explicitly says this was not a randomized comparison, and allocation is not stated.

The enrollment is 26. That figure is the registry’s enrollment entry; the number analyzed for the primary endpoint is not reported in the registry record. The primary analysis population is described as a full analysis set of participants who received at least one dose, excluding participants whose status epilepticus or repetitive status epilepticus/cluster seizure was determined on electroencephalography. The record does not give the size of this population or explain how many people were excluded for that reason.

The study began in 2014-11, reached primary completion in 2016-08, and is marked completed. Its primary outcome concerns seizure freedom after the initial dose. Secondary outcomes include seizure-free intervals after any dose, longer seizure-free intervals after administration of either the initial or any dose, time to seizure resolution, time to relapse, and treatment-emergent adverse events and serious adverse events. These outcome listings describe what was assessed; they do not themselves report the results. The registry record lists no analysis entries, and does not report the detailed analysis plan.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all participants who received at least 1 dose of study drug, excluded those participants whose status epilepticus (SE) or repetitive SE/cluster seizure was determined on the electroencephalography (EEG).

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: Safety analysis set included all participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieved Seizure Free Interval of At Least 30 Minutes After Initial Dose (Dose 1) of Study Drug, measured over 30 minutes post Dose 1.

The primary endpoint is the percentage of participants who achieved a seizure-free interval of at least 30 minutes after the initial dose, designated Dose 1. The registry’s definition requires the initial seizure to stop within 10 minutes after the dose and the participant to remain seizure-free for at least 30 minutes after completion of the dose. The stated timeframe is 30 minutes post Dose 1.

This is a binary participant-level outcome: each participant either meets the stated success definition or does not. Reporting a percentage is a way to describe how often the defined response occurred in the analysis population. As a general statistical point, a clearly operationalized endpoint helps make the outcome interpretable by specifying what counts as success and when it is assessed. Here, the endpoint combines seizure cessation soon after the initial dose with a period of continued seizure freedom.

The registry record does not report the number or percentage of participants meeting this definition, nor a confidence interval for the primary outcome. Consequently, the endpoint definition can be described, but its observed frequency and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a percentage, which represents the proportion of participants in the analysis population meeting the endpoint definition. The endpoint is binary at the participant level: the stated criteria are either met or not met. This approach is common when an outcome can be defined as a response or non-response. In this study, the definition combines timely seizure cessation after the initial dose with a specified subsequent seizure-free interval.

The registry lists a 95% confidence interval as the dispersion measure for the primary outcome, but the estimate and interval are not reported in the registry record. In general, a confidence interval communicates the precision of an estimate by giving a range of values compatible with the data under the statistical method used. A narrower interval indicates greater precision than a wider interval, but neither guarantees that the interval contains the true value. The interval’s width depends on factors including the number of participants contributing data and the observed response frequency. Because the primary estimate, analyzed denominator, and interval are not reported, the precision of this outcome cannot be evaluated.

The record does not identify the method used to calculate that interval. Different methods for binary proportions can behave differently, particularly when the denominator is limited or the observed proportion is near an endpoint of its possible range. This is a general methodological consideration, not a claim about the method used in this study. The registry record does not report whether an exact, score-based, or other interval procedure was used.

The full analysis set is described as including participants who received at least one dose, while excluding participants whose status epilepticus or repetitive status epilepticus/cluster seizure was determined on electroencephalography. In general, defining an analysis population in advance matters because the included participants determine which observations contribute to the estimate. The record does not report the population’s size, individual participant data, or how the exclusion was applied in practice. It also does not report how missing endpoint assessments were handled.

The study’s open-label, non-controlled design has important interpretive consequences. In general, an open-label design means treatment masking is absent, while a non-controlled design lacks a comparison group for estimating differences in outcomes between assigned treatments. The record explicitly says this was not a randomized comparison and does not state allocation. Therefore, a treatment contrast cannot be inferred from the listed study arm. General statistical methods for controlled comparisons cannot be assumed to have been applied, and the registry record does not describe an adjusted or unadjusted comparative model.

The registry lists no analysis entries. It does not report whether there were interim analyses, what hypothesis tests were planned, or whether any adjustment for multiple testing was intended. Those details are not reported in the registry record, so no particular test, model, or testing strategy should be attributed to the study. The existence of multiple listed outcomes alone does not establish that all were confirmatory or that they were tested in a particular order.

Planning calculations based on an observed effect are illustrations rather than evidence of the study’s original design or an observed probability of success. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. The record does not report that these were the trial’s design assumptions; indeed, the study is described as non-controlled, and the planning illustration must not be read as a randomized two-arm design for this trial. Sample-size calculations are planning quantities, not observed power. The record does not provide the primary effect estimate needed to assess such an illustration in this interpretation.

For time-to-event outcomes, general statistical methods account for the timing of events and may also need to address participants whose event time is not observed during follow-up. The registry lists time to resolution and time to relapse, but the registry entries do not report their estimates, censoring details, or analysis methods. The registry’s general note distinguishes total events for time-to-event planning from participants per arm for other planning; it does not supply results for the outcomes in this trial.

Finally, over-dispersion is a general issue for count outcomes when variability exceeds what a simple count model expects. It can affect uncertainty estimates and the suitability of a model. The primary endpoint is described as a percentage, not as an event count rate, and the registry record does not report an over-dispersed model or any other model choice. Such concepts explain possible statistical considerations but cannot fill in methods that are not reported.

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("Lorazepam")
n      <- c(25)
events <- c(12)
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  Lorazepam  25  12  48.0  27.8  68.7  30.0  66.5  29.9  66.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes. The secondary measures cover seizure-free intervals after any dose, extended seizure-free intervals, time to resolution, time to relapse, and adverse events. Considering multiple outcomes raises a general multiplicity issue: when many hypotheses are examined, the chance of at least one apparently notable result can increase if each is assessed separately. How to handle that issue depends on which outcomes are confirmatory, the planned testing strategy, and whether any adjustment or hierarchy is specified.

The registry record lists no analysis entries and does not report a multiplicity strategy, such as an adjustment, a testing sequence, or a distinction between confirmatory and exploratory outcomes. It is therefore not possible to determine how the study intended to interpret results across its outcomes. The outcome list alone does not establish that every listed measure was subject to formal hypothesis testing.

Missing-data handling is also not reported in the registry record. The primary population definition describes who was eligible for the full analysis set, including an electroencephalography-related exclusion, but does not explain how missing assessments, incomplete follow-up, or endpoint status that could not be determined were treated. No imputation approach or sensitivity analysis is reported in the available record.

The size of the primary analysis population and the number of participants with an observed endpoint are not reported. This leaves the denominator and any potential impact of missing outcome data unclear. These gaps limit assessment of both the primary estimate’s precision and the robustness of conclusions across outcomes. They should not be filled by assuming a particular analysis population, missing-data method, or multiplicity correction.

12. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia aspiration (3.8%).

For the lorazepam group, the registry lists 26 participants at risk for serious adverse events, with 1 affected by a serious adverse event. It lists 26 participants at risk for other adverse events, with 12 affected. These are participant counts in the registry record; they are not a comparison between treatment groups. The record does not report deaths.

Pneumonia aspiration is the serious adverse event term listed with a percentage of 3.8%. This term-specific figure should be read as the registry’s reported value, not as a broader estimate of overall risk. A participant-level count and an event term are different summaries: the former indicates how many participants were affected in the category, while a term describes the type of event recorded.

Because the study is non-controlled, these figures cannot show whether serious adverse events were more or less frequent than under another treatment or no treatment. The registry record does not provide further detail on event timing, severity beyond the serious classification, relatedness assessment, or participant-level overlap between the serious and other adverse-event categories. The counts describe what was recorded in the lorazepam group and do not, on their own, establish causation.

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

The record establishes that the study evaluated intravenous lorazepam in people with status epilepticus or repetitive status epilepticus, and that its primary outcome was a defined seizure-free response after the initial dose. It also gives the study’s enrollment entry, the analysis-population definition, and selected adverse-event counts. These details help clarify what the study set out to measure and how the primary response was defined.

The primary outcome result itself is not reported in the registry record. There is no reported percentage meeting the success definition, no reported confidence interval, and no stated analyzed denominator. Consequently, the record does not allow the frequency of the primary response or its precision to be assessed. The endpoint description must not be mistaken for evidence about how often the endpoint occurred.

The study’s open-label, non-controlled design also limits what can be inferred. Since no comparator is described and the registry says this was not a randomized comparison, the record does not estimate a relative effect against another treatment. The listed adverse-event counts similarly describe the lorazepam group without a comparison that would support a comparative safety estimate.

In general, a single-arm outcome can be useful as a description of what was observed in a specified study population, but it cannot by itself distinguish treatment effects from other explanations for the outcome. The registry record does not provide details that would resolve such explanations. Nor does it report the analysis plan, missing-data handling, or multiplicity strategy needed to assess how the outcomes were analyzed.

The appropriate statistical reading is therefore limited: the question and outcome definitions are available, as are selected safety counts, but the principal efficacy result and its uncertainty are not reported. No conclusion about treatment benefit or lack of benefit can be drawn from this record alone.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an endpoint result are not interchangeable. The primary outcome is defined with specific criteria for seizure cessation and continued seizure freedom after the initial dose. That definition makes the intended response measurable, but interpretation still depends on the observed percentage, its denominator, and its uncertainty. Those primary result details are not reported in the registry record.

The trial also highlights the importance of design when interpreting a clinical outcome. Open-label, non-controlled studies can describe what happened among participants receiving an intervention, but without a comparator they do not provide a randomized contrast. The registry explicitly notes that this was not a randomized comparison and that allocation was not stated. A parallel design label does not supply a missing comparison group.

The distinction between enrollment and analysis population is another statistical point. The enrollment entry is 26, while the full analysis set has an eligibility definition involving receipt of at least one dose and an electroencephalography-related exclusion. Since the analyzed denominator is not reported, the enrollment entry cannot stand in for the number contributing to the primary estimate.

Finally, the record lists multiple secondary outcomes and safety measures but does not report analysis entries, a multiplicity strategy, or missing-data methods. These omissions matter because outcome selection, uncertainty, and incomplete assessment can shape how results should be interpreted. The case is a useful reminder that a detailed outcome definition and safety counts do not replace complete reporting of estimates, confidence intervals, analysis populations, and methods.

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 is that the registry record does not report the primary endpoint result. It gives the endpoint definition and states that a 95% confidence interval was the dispersion measure, but no estimate or interval is reported. The primary analysis population’s size and the number of participants meeting the endpoint are also not reported, so the result cannot be reconstructed from the enrollment entry.

The non-controlled, open-label design limits comparative interpretation. No comparator arm is described, and the registry states that the study was not a randomized comparison. Allocation is not stated. Consequently, the posted information cannot establish a relative effect against another intervention, and the safety figures cannot be interpreted as comparative risks.

The record does not report detailed analysis methods, missing-data handling, or a strategy for interpreting multiple outcomes. It also does not report results for the listed secondary outcomes in the registry entries. The primary population definition includes an electroencephalography-related exclusion, but the number excluded and the resulting analysis population size are not reported.

Safety reporting is limited to selected counts and the serious-event term pneumonia aspiration, with deaths not reported in the registry record. Further details about timing, relatedness, severity beyond the serious classification, and overlap between event categories are not reported. These limitations do not establish that such information was absent from the study conduct; they indicate that it is not reported in the registry record used for this interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lorazepam for the Treatment of Status Epilepticus or Repetitive Status Epilepticus in Japan — NCT02239380.
• Registry record last updated 2019-02-18; status last verified 2018-10.
• Results first posted 2019-02-18.
• 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

This completed Phase 3 study evaluated intravenous lorazepam for status epilepticus or repetitive status epilepticus in Japan. The registry describes it as multicenter, open-label, and non-controlled, with enrollment of 26. The primary endpoint was the percentage achieving at least 30 minutes of seizure freedom after the initial dose, under a definition that also required the seizure to stop within 10 minutes after dosing. The primary result, analyzed denominator, and confidence interval are not reported in the registry record.

The record lists secondary seizure and safety outcomes, but no analysis entries. For the lorazepam group, 1 participant is listed with a serious adverse event and 12 with other adverse events; pneumonia aspiration is listed as a serious event term at 3.8%. Deaths are not reported in the registry record. With no comparator described, neither efficacy nor safety can be interpreted as a treatment-group contrast.