Seizure Prophylaxis in Patients With Glioma or Brain Metastasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Seizure Prophylaxis in Patients With Glioma or Brain Metastasis (NCT03436433), a randomized phase 2 study. The primary outcome is Percentage of Patients With an ED Visit/Hospital Readmission Within 30 Days of Craniotomy.

2. Clinical Question

3. Trial Design

NCT03436433 is a phase II randomized, open-label, parallel-group trial sponsored by Duke University. Its official title describes seizure prophylaxis in brain tumor patients undergoing a neurosurgical procedure. The registry lists glioma and brain tumor conditions and includes brain metastasis in the trial summary. The planned strategies were lacosamide, levetiracetam, and no anti-epileptic drug. Masking was listed as none, so the trial was not described as blinded.

The registry reports enrollment of 4 and a status of terminated. The recorded start date is 2019-01-31, and the primary completion date is 2020-12-04. The reason for termination is not reported in the registry record. Nor does the record explain whether termination was related to recruitment, feasibility, safety, or another consideration. The dates and status alone do not establish why the study ended.

The protocol summary describes surgery for suspected new, recurrent, or transformed glioma, WHO grade I-IV, or brain metastasis. Eligible procedures in that summary include gross-total resection, sub-total resection, and biopsy; the primary endpoint, however, is framed around craniotomy. The registry does not report how many participants underwent each procedure or their tumor diagnoses and characteristics.

Posted primary outcome counts are 0.0 participants for lacosamide, 0.0 for levetiracetam, and 1.0 for no anti-epileptic drug; the corresponding group sizes are 1.0, 2.0, and 1.0. The record does not post an inferential analysis or a comparative effect estimate. Assignment concealment, the randomization sequence, adherence, and analysis-population definitions are not reported in the registry record.

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

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 Percentage of Patients With an ED Visit/Hospital Readmission Within 30 Days of Craniotomy, measured over 30 days following surgery.

The primary endpoint concerns whether a participant had an emergency department visit or hospital readmission within 30 days following craniotomy. It is a binary, participant-level outcome: each participant either had at least one qualifying event during the specified period or did not. The registry labels the measure as a percentage but identifies its parameter as a count of participants. The posted group values are reported as counts, not as a comparative percentage effect.

This type of endpoint can capture unplanned use of acute hospital care after surgery. It is relevant to the protocol’s stated aim of assessing perioperative seizure prophylaxis because an emergency visit or readmission may occur during the postoperative period in which the study was observing outcomes. However, the endpoint combines two kinds of healthcare encounters and does not, in the posted description, specify that every event must be caused by a seizure. It should therefore be read as an all-cause encounter outcome as described, not as a direct count of postoperative seizures.

The registry lists the timeframe as 30 days following surgery. It does not provide event-level details, reasons for visits or readmissions, or a separate result for each component of the combined endpoint. Nor does it report missing follow-up information or how such information was handled. The small posted group counts make the observed event pattern highly limited as a basis for estimating how outcomes might compare in a larger population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as binary and describes its parameter as a count of participants. A binary outcome records whether a defined event occurred during the stated follow-up period. For this trial, the event combines an emergency department visit or hospital readmission within 30 days following craniotomy. The posted group values therefore describe event counts, rather than a continuous measurement such as length of stay.

What does a count show?

A count is a direct description of the observed participants, but its meaning depends on the group size and the outcome definition. Counts can be used to estimate the probability of an event in a target population, but an estimate based on few observations is imprecise. When no event is observed, uncertainty remains about how often an event might occur in the wider population. A zero count is not proof of zero risk. In this record, the arm sizes and event counts are small, so the results are best treated as a description of the observed trial participants.

What would a comparative estimate add?

A comparative analysis would quantify how the event frequency differs between specified groups and would show uncertainty around that estimate. A confidence interval is a range of values consistent with the data and the statistical method used; it communicates precision rather than guaranteeing that the true effect lies within the reported range. The registry record does not report a confidence interval or another comparative effect estimate for the primary outcome. It also does not report a p-value or an analysis model. A numerical comparison should therefore not be inferred from the separate counts.

There are three assigned strategies: lacosamide, levetiracetam, and no anti-epileptic drug. A comparison among three groups may involve several possible pairwise contrasts or an overall test, but the record does not specify which comparisons were planned for formal inference. It reports zero analyses. As a result, the posted outcome counts do not identify a sponsor-selected statistical conclusion or reveal whether adjustment for covariates was intended.

Why do small groups affect precision?

With sparse binary outcomes, adding or removing an event can materially change the apparent pattern. Conventional approximations that work better with larger samples may perform poorly when group sizes and event counts are limited. Exact methods or methods designed for sparse data can sometimes be considered, but the record does not say which method, if any, was planned or used. It would be inappropriate to present an unreported method or a recalculated comparison as the trial’s own analysis.

Planning illustrations based on an observed effect are not observed power. They describe hypothetical future sample sizes under stated assumptions; they do not measure the probability that this completed trial detected a real effect. The record’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Those assumptions describe an illustration and do not establish the original trial’s design rationale or statistical plan. The registry record does not report the original sample-size justification.

What is not documented about the analysis?

The record does not report an analysis population, such as whether participants were analyzed according to assigned group or according to treatment received. It does not describe handling of missing outcomes, protocol deviations, or incomplete follow-up. It also does not give a model specification, covariate adjustment, interim-analysis plan, or multiplicity procedure. These are not details that can be recovered from the event counts. Their absence limits reproducibility and prevents readers from assessing whether a prespecified analysis was followed.

Finally, the endpoint combines emergency visits and hospital readmissions. A single combined count can be useful for describing whether either kind of encounter occurred, but it does not reveal which component drove the result, the reason for each encounter, or whether the encounter was seizure-related. Component-specific and event-level information is not reported in the registry record. The statistical interpretation should remain tied to the endpoint as registered, rather than extending the result to a more specific outcome.

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("Lacosamide", "Levetiracetam", "No Anti-epileptic")
n      <- c(1, 2, 1)
events <- c(0, 0, 1)
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  Lacosamide  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Levetiracetam  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  No Anti-epileptic  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The trial includes three assigned strategies and describes a primary endpoint, a safety endpoint, and exploratory outcomes. The registry record does not report a multiplicity strategy for controlling the chance of false-positive findings across several comparisons or outcomes. It also reports zero analyses, so there is no posted inferential result to assess against any such strategy. The record does not state which pairwise contrasts, if any, were prespecified as primary comparisons.

One secondary outcome is listed: participants with an adverse event within the first 30 days after craniotomy. The protocol summary also names exploratory outcomes, including admission duration, postoperative provider communications, and patient risk factors associated with postoperative seizure. Results for those exploratory outcomes are not included in the posted information described in the registry record. A listed outcome should not be mistaken for a reported analysis.

Missing-data methods are not reported in the registry record. It does not say whether all participants completed follow-up, how an unavailable 30-day outcome was classified, or whether any imputation or sensitivity analysis was used. The number of participants included in an analysis is also not separately reported. These omissions matter because the primary endpoint depends on observing emergency visits or readmissions during a defined period, and incomplete ascertainment could affect the observed counts.

Analysis populations and adherence handling are likewise not reported. The record does not identify an intention-to-treat, per-protocol, or other analysis set. It does not describe whether participants who did not follow assigned treatment would remain analyzed in their randomized group. Readers should therefore interpret the posted numbers as reported outcome counts, without assuming an analysis convention or a missing-data procedure.

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 non-serious adverse event terms

The serious adverse event fields report zero serious adverse events in each group. The record gives the at-risk counts as 1 for lacosamide, 2 for levetiracetam, and 1 for no anti-epileptic drug; the corresponding serious-event counts are 0, 0, and 0. Deaths are also reported as 0 in each group. These are descriptive counts from a small enrolled group, not precise estimates of comparative safety.

The record separately reports other adverse events: 1 affected participant among 1 at risk with lacosamide, 2 among 2 at risk with levetiracetam, and 1 among 1 at risk with no anti-epileptic drug. These fields do not provide event descriptions in the information, and the serious-event terms list is empty. The registry therefore does not allow a reader to assess the nature, severity, timing, or relatedness of the reported non-serious events.

Zero serious events observed does not establish that serious events cannot occur, especially with very limited exposure. Nor do the other-adverse-event counts establish that the strategies differ in safety. The record does not report a statistical safety comparison or detailed definitions and attribution for these events.

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

The registry record gives a small descriptive result for the primary endpoint: the posted event count is 0.0 in the lacosamide group, 0.0 in the levetiracetam group, and 1.0 in the no-anti-epileptic-drug group. The corresponding group sizes are 1.0, 2.0, and 1.0. This describes the recorded experience of participants enrolled in this trial, using the registered combined endpoint of emergency department visits or hospital readmissions within 30 days following craniotomy.

It does not establish that one strategy is better than another. No comparative estimate, uncertainty interval, or inferential analysis is reported, and the small groups cannot support a precise population-level conclusion. The observed pattern may be strongly affected by individual outcomes and by chance differences among groups. It should not be read as proof that a strategy prevents events, causes events, or has no effect.

The outcome also does not directly count postoperative seizures. The registry’s primary endpoint is an acute-care encounter, and the record does not give the reasons for those encounters or separate emergency visits from readmissions. Thus, conclusions about seizure frequency or seizure prevention are not supported by these posted counts.

The trial’s safety information is similarly descriptive. Zero serious adverse events are reported in the groups, while other adverse events are recorded in each group. With the limited enrollment and no detailed event descriptions or statistical comparison, these data cannot establish comparative safety. The registry’s terminated status and lack of a reported termination reason add context but do not explain the result or its limitations.

Overall, the posted results are useful as a record of what was observed in this trial, but they are not a reliable estimate of how the three strategies would compare in a larger clinical population.

14. Why This Trial Matters Statistically

This trial illustrates how a randomized design and a small amount of outcome information can coexist. Randomization is intended to support comparisons between assigned groups, but it does not make a very small set of observations precise. With enrollment of 4, the primary result is dominated by the recorded experience of individual participants, and there is little information with which to estimate uncertainty or assess balance across groups.

The study also illustrates why reporting an endpoint count is not the same as reporting a treatment effect. Counts show what happened in the enrolled groups. A comparative estimate would need to define the contrast, quantify the difference or other chosen effect measure, and report uncertainty. The registry record provides none of those inferential results. Readers can describe the observed pattern without converting it into a claim about the relative effect of the strategies.

The combined endpoint raises a second statistical issue: an outcome may be relevant and measurable yet capture more than one underlying event type. Emergency department visits and hospital readmissions are grouped together, and the posted result does not separate them or identify their causes. That limits the specificity of any interpretation, particularly when the protocol’s broader rationale concerns seizure prophylaxis.

Finally, the record demonstrates the value of complete reporting. Information about the analysis plan, missing outcomes, comparison strategy, and reason for termination would help readers distinguish a planned evaluation from a descriptive record of a trial that ended with limited enrollment. Those details are not reported, so the conclusions must remain correspondingly narrow.

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 main limitation is the very small enrollment: the registry reports 4 participants across three assigned strategies. The arm-specific outcome counts are therefore sparse, and the record does not provide a comparative effect estimate or uncertainty interval. The findings cannot precisely characterize event frequencies or differences among strategies in a broader population.

The trial is listed as terminated, but the reason is not reported in the registry record. This prevents readers from determining whether termination reflected feasibility, recruitment, a decision about the study question, or another circumstance. The record does not provide enough information to infer the intended recruitment target or whether the trial ended as planned.

The registry does not report participant characteristics, procedure-specific enrollment, medication schedules, adherence, or the method used to ascertain emergency visits and readmissions. It does not separate the endpoint components or state whether encounters were related to seizures. These gaps limit assessment of clinical comparability and of how completely the registered endpoint represents the intended question.

No inferential analyses are posted. The analysis population, missing-data handling, comparison plan, and multiplicity approach are not reported in the registry record. The record also does not provide detailed adverse-event terms or event attribution. As a result, the available safety counts cannot support detailed interpretation, and no formal conclusion about efficacy or safety can be drawn from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Seizure Prophylaxis in Patients With Glioma or Brain Metastasis — NCT03436433.
• Registry record last updated 2023-04-13; status last verified 2023-04.
• Results first posted 2021-12-30.
• 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

NCT03436433 is a randomized, open-label, parallel-group phase II trial sponsored by Duke University. It evaluated lacosamide, levetiracetam, and no anti-epileptic drug for seizure prophylaxis around neurosurgical procedures in patients with suspected glioma or brain metastasis. Enrollment was 4, and the registry lists the study as terminated. The recorded start date is 2019-01-31, and the primary completion date is 2020-12-04.

The primary endpoint was an emergency department visit or hospital readmission within 30 days following craniotomy. Posted counts were 0.0 participants for lacosamide, 0.0 for levetiracetam, and 1.0 for no anti-epileptic drug. The registry reports no analyses or comparative effect estimate. Serious adverse events and deaths were reported as 0 in each group; other adverse events were also recorded. The reason for termination, analysis methods, and missing-data procedures are not reported in the registry record.