This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Antiseizure Medication in Seizure Networks at Early Acute Brain Injury (NCT06081283), a non-randomized phase 4 study. The primary outcome is Pre and Post-intervention Seizure Networks Power Spectrum Medians.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT06081283 |
| Phase | Phase 4 |
| Condition | Brain Injuries, Acute, Brain Injuries, Traumatic, Brain Ischemia |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of North Carolina, Chapel Hill |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with moderate or severe acute brain injury and suppression of consciousness. The registry lists conditions including traumatic brain injury, brain ischemia, hypoxia, cardiac arrest, stroke, intracranial hemorrhage, coma, and persistent vegetative state. The primary outcome does not apply to seizure-network-negative participants, and the registry says no data were collected for that group.
Intervention
Participants identified as seizure-network-positive were to receive loading and maintenance doses of two antiseizure medication regimens from a study list that includes phenobarbital sodium, levetiracetam, lacosamide, valproate sodium, and fosphenytoin. The registry record does not identify which two regimens each participant received.
Comparator
The planned assessment compares each seizure-network-positive participant’s pre-intervention and post-intervention resting-state functional MRI. Seizure-network-negative participants did not receive interventions after their initial scan and did not have repeat scans. This is not a randomized, like-for-like comparison between treatment and control groups.
Primary question
The primary outcome concerns whether the median power spectrum of seizure networks differs between pre-intervention and post-intervention resting-state functional MRI. The broader study also asks whether seizure networks are present in the target population and whether typical resting-state network connectivity changes after intervention. Outcome results are not reported in the registry record.
3. Trial Design
This is a Phase 4, open-label pilot trial with non-randomized allocation and a sequential model. The registry lists enrollment of 5 and a status of terminated. The study start date is 2023-11-20, and the primary completion date is 2024-12-22. The reason for termination is not reported in the registry record.
The study description divides participants according to whether the initial resting-state functional MRI identified a seizure network. Seizure-network-positive participants were to receive two medication regimens from the study list and have a post-intervention scan. The description says treatment was to occur within six days of the first scan. Seizure-network-negative participants were not to receive intervention, repeat MRI, or repeat EEG. The record does not provide enough detail to reconstruct the complete sequence of procedures or the specific drug regimens received.
Because the groups were defined by seizure-network status and had different procedures, the negative group is not a randomized control group. Any differences between the groups could reflect their initial classification and other differences, as well as the different follow-up procedures. The main pre/post question is instead a within-participant comparison among seizure-network-positive participants.
The registry lists secondary outcomes concerning seizure-network presence on the first scan, follow-up EEG improvement, typical-network connectivity, enrollment rate, and dropout rate. It does not report results for these outcomes. A sample-size justification, detailed statistical analysis plan, and reason for termination 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.
Before assignment: No participants were enrolled with a Glasgow Coma Scale (GCS) score of 9 to 12. The intervention phase occurs between resting state functional magnetic resonance imaging (rs-fMRI#1) and the day of follow-up rs-fMRI#2 and repeated EEG. The intervention is considered complete and the follow-up tests can be done if the patient received the study antiseizure medication (ASM) for at least 72 hours after the loading dose, and the second scan was done within 72 hours of the last intervention ASM dose.
Overall Study
| Stage | Seizure Network Positive Subjects | Seizure Network Negative Subjects |
|---|---|---|
| STARTED | 3 | 2 |
| Received Initial Phenobarbital Sodium Followed by Lacosamide | 1 | 0 |
| Completed Initial Phenobarbital Sodium Followed by Lacosamide | 1 | 0 |
| Received Initial Levetiracetam Followed by Lacosamide | 2 | 0 |
| Completed Initial Levetiracetam Followed by Lacosamide | 2 | 0 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 2 | 2 |
Analysis population for the primary outcome, as defined in the registry: This outcome does not apply to the Seizure Network Negative Subjects; therefore, no data were collected for this group.
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.
| Characteristic | Unit | Seizure Network Positive Subjects | Seizure Network Negative Subjects | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 2 | 5 | |
| Age, Categorical: <=18 years | Participants | 1 | 0 | 1 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 2 | 4 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | Participants | 3 | 2 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Pre and Post-intervention Seizure Networks Power Spectrum Medians, measured over At the time of the second study rs-fMRI scan, which acquisition can be from 3 to 13 days after the intervention start date..
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | Hz/10^2 |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the median of a seizure-network power-spectrum measure before and after intervention. The registry describes power spectral analysis as a way to examine patterns in blood-oxygen-level-dependent signal power across frequencies. The seizure-network measure is based on the power spectra of independent components identified as suspected seizure-onset zones, normalized by spatial volume. The pre- and post-intervention medians are derived from a normalized, volume-adjusted area under the seizure-network power-spectrum curve above 6.78 Hz/100. The stated unit is Hz/10^2, and the dispersion measure is the full range.
Resting-state functional MRI provides a way to examine brain connectivity without requiring a task. In general, a frequency-based summary can describe a feature of the measured signal that may be relevant to the study’s proposed seizure-network pattern. A median is a measure of central tendency that is less influenced by extreme observations than a mean, while the full range describes the span from the lowest to highest observed value. These are general statistical interpretations, not evidence that the measure is clinically meaningful or that a change has occurred.
The endpoint is restricted to seizure-network-positive participants; the registry says it does not apply to seizure-network-negative participants and that no data were collected for that group. The registry record does not report the pre- or post-intervention medians, the full range values, or a statistical comparison between them.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a small pilot study with enrollment of 5, but it does not report numerical results for the primary outcome. There are no posted pre-intervention or post-intervention medians, full ranges, effect estimates, confidence intervals, or p-values in the record. Consequently, the direction and precision of any change in the seizure-network power-spectrum measure cannot be assessed from the registry information.
The study’s main comparison is pre-intervention versus post-intervention measurement among seizure-network-positive participants. The registry says the second scan could be acquired from 3 to 13 days after the intervention start date. This timing range means that the measurement interval was not necessarily identical for every participant. Without individual timing and outcome data, the extent to which timing could influence the observed measurement is not reported in the registry record.
The seizure-network-negative group does not provide a like-for-like control for the primary outcome. Those participants did not receive intervention or a repeat MRI, and the primary outcome was not collected for them. Their classification was based on the initial scan, so comparing them with positive participants would not isolate a treatment effect. The study is non-randomized and open-label, which also means that treatment allocation and outcome assessment were not blinded according to the registry description.
The record reports no statistical analyses, with n analyses listed as 0. It therefore does not establish whether a pre/post comparison was tested, how uncertainty was estimated, or whether results were adjusted for any other factors. Results for the listed secondary outcomes are also not reported in the registry record. The status is terminated, but the reason and whether termination affected planned follow-up are not reported.
The posted sample-size illustrations are planning scenarios, not observed power. They are described as using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as a fraction of the observed effect. The registry record does not identify those calculations as the trial’s original design justification. No inference about treatment benefit or harm follows from a planning illustration.
Overall, the available registry information supports a description of the research question and design, but not a conclusion about whether the endpoint changed or how precisely it was measured. The sponsor’s own analysis is not reported in the registry record, so there is no reported analysis to interpret or compare with a recalculation.
9. Statistical Methods Explained
The registry describes an imaging-based outcome rather than a conventional clinical event endpoint. Its primary measure is a median derived from the power spectrum of resting-state functional MRI signal components judged to be seizure-network-related. The methods description says scans were co-registered to anatomical T1 images, visually inspected, and analyzed using independent component analysis with the FMRIB Software Library tool MELODIC. Components were evaluated for suspected seizure-onset zones using spatial and temporal features. These are the procedures described in the registry; further details about reproducibility, thresholds for component classification, or analyst blinding are not reported.
What does the median represent?
In general, a median is the middle value after measurements are ordered. It can be useful when measurements are skewed or include extreme values, because an extreme observation has less influence on the median than it would on the mean. The registry identifies the median as the summary measure, but does not report the actual pre-intervention or post-intervention values. Without those observations, it is not possible to assess the distribution or determine how representative the median is of the participant-level measurements.
What does the full range add?
The full range records the lowest and highest values. In general, it gives a simple indication of spread, but it can be strongly affected by extreme observations and does not show how values are distributed between the endpoints. With a small pilot, a range may be especially sensitive to individual observations. This is a general statistical consideration; the registry does not report the range values needed to assess variability in this study.
How should a pre/post comparison be understood?
A within-participant comparison uses each participant’s pre-intervention measurement as a reference for their post-intervention measurement. In general, this can account for stable differences between participants, because the comparison is made within the same person. It does not, by itself, control for changes over time, measurement variability, concurrent care, or other time-varying influences. A non-randomized pre/post study therefore describes change over time but does not automatically identify the intervention as the cause of any change.
The registry describes the post-intervention scan as occurring from 3 to 13 days after intervention start. Variation in measurement timing can matter if the measured signal changes over time, although the record does not report whether that possibility was addressed in analysis. It also does not report a statistical model for paired observations, an estimate of within-participant variability, or uncertainty intervals around the pre/post comparison.
Why does the group structure matter?
Seizure-network-positive and seizure-network-negative participants were treated differently. Positive participants were assigned intervention and follow-up imaging in the study description; negative participants did not receive intervention or repeat imaging. This is a classification-based, non-randomized design, not a treatment-versus-control comparison with comparable measurement schedules. The negative group cannot serve as a direct control for the primary endpoint because that endpoint was not collected for them.
In general, random allocation can help balance measured and unmeasured characteristics between treatment groups, while masking can reduce some opportunities for expectations to influence care or assessment. Neither randomization nor masking is part of the registry description. This does not determine the direction of bias, but it limits the strength of causal conclusions that can be drawn from any observed pre/post change.
What do the planning calculations mean?
The sample-size illustrations are described as planning calculations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The requested detectable effect is expressed as a fraction of the observed effect. For non-time-to-event outcomes, the calculations are described in participants per arm for 80% power or other stated power levels; time-to-event calculations are described as total events. No specific illustration values are reported in the registry record available for this analysis.
In general, a planning calculation estimates the sample size that would be needed under stated assumptions. It is not the probability that the completed study detected an effect, and it is not observed power. A calculation based on an observed effect can be particularly uncertain when the study is small, because the estimated effect may be unstable. The registry does not report a sample-size justification used to design this trial, so the illustrations should not be treated as evidence of the study’s original design rationale.
What analysis details are unavailable?
The registry reports no analyses. It does not report a statistical test, model, confidence interval method, handling of repeated measures, adjustment for covariates, or approach to missing observations. It also does not report whether any interim analyses occurred. These are not details that can be inferred from the stated endpoint or from the imaging workflow. In general, confidence intervals communicate the range of values compatible with an estimate under a specified method; without reported estimates and intervals, the precision of the primary result cannot be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes: the primary pre/post seizure-network power-spectrum measure and secondary outcomes concerning initial seizure-network presence, follow-up EEG improvement, typical resting-state network connectivity, enrollment, and dropout. It reports n analyses as 0 and does not describe a statistical analysis plan. Whether the outcomes were tested, how many comparisons were planned, or whether multiplicity was addressed is not reported in the registry record.
In general, when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase. Prespecifying a primary outcome and analysis can help readers distinguish confirmatory questions from exploratory ones. The record identifies a primary outcome but does not report analysis details or an approach to multiple comparisons. No adjustment method should be assumed.
Missing-data counts and reasons are not reported in the registry record. The listed dropout-rate outcome does not establish how many participants completed each scan or whether any observations were unavailable. The record also does not describe an analysis population, such as whether all enrolled participants or only those with both scans would be included in the primary analysis. The primary endpoint explicitly excludes seizure-network-negative participants, for whom no data were collected.
In general, missing observations can affect estimates when the reasons for missingness are related to outcome values, health status, or study procedures. The direction and magnitude of any such effect cannot be assessed without participant flow and missingness information. The registry does not report imputation, sensitivity analyses, or rules for excluding incomplete observations.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Seizure Network Positive Subjects | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Seizure Network Positive Subjects | 1 of 3 |
| Seizure Network Negative Subjects | 2 of 2 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Seizure Network Positive Subjects | 0 of 3 |
| Seizure Network Negative Subjects | 0 of 0 |
The registry reports serious adverse event counts separately for seizure-network-positive and seizure-network-negative subjects. For the positive group, the listed number at risk for serious adverse events is 3 and the number affected is 0. For the negative group, the listed number at risk is 0 and the number affected is 0. A zero count in a group with no participants listed at risk does not provide information about the frequency of serious adverse events in that group.
The record also lists 0 other adverse events among 3 subjects at risk in the positive group, and 0 among 0 at risk in the negative group. It reports deaths of 1 in the positive group and 2 in the negative group. These figures are descriptive registry counts. They do not establish whether a death or adverse event was caused by study medication, the underlying injury, or another factor; causal attribution is not reported in the registry record.
The adverse-event figures do not include event descriptions or timing in the information, and the registry lists no top serious adverse-event terms. Small numbers and the absence of detail limit interpretation. The record does not report a safety analysis plan or comparative safety estimate. The groups also differ in intervention and follow-up, so their counts should not be read as a randomized safety comparison.
12. What the Result Does, and Does Not, Mean
The study addresses whether a seizure-network measure derived from resting-state functional MRI changes after antiseizure medication in people with acute brain injury who have a seizure network identified on an initial scan. It also describes questions about how often seizure networks are found and whether EEG or typical-network connectivity changes. These are research questions, not findings: outcome results are not reported in the registry record.
The study design can support a descriptive account of measurements before and after intervention if those measurements and analyses are reported. A pre/post change, if observed, would not alone show that medication caused it. Changes over time, differences in scan timing, measurement variability, and other influences could also contribute. The absence of randomization, masking, and a like-for-like control comparison limits causal interpretation.
The primary outcome applies only to seizure-network-positive participants. The seizure-network-negative group was not treated or rescanned according to the registry description, so it cannot establish what would have happened to positive participants without intervention. The registry record does not provide the primary outcome values, uncertainty estimates, or analysis details needed to judge the size, direction, or precision of any change.
The reported safety counts should also be interpreted as descriptive. They do not establish a treatment-related cause, and the groups were not designed as comparable safety arms. The status of terminated does not explain why the study ended or what effect, if any, termination had on data collection.
Accordingly, the registry record establishes the study’s purpose, broad methods, and some safety counts, but does not permit a conclusion about an imaging effect, clinical benefit, or causal safety relationship. Any sample-size calculations are planning illustrations rather than observed power or evidence of a result.
13. Why This Trial Matters Statistically
This trial raises statistical questions that are common in early imaging studies: how to define a signal-derived endpoint, how to compare repeated measurements, and how to communicate uncertainty when the study is small. The use of a pre/post design makes participant-level pairing relevant, while the lack of a comparable untreated group limits causal interpretation. These design features affect what the data can establish, independently of the scientific interest of the question.
The distinction between seizure-network-positive and seizure-network-negative participants is central. The primary measure is not collected for the negative group, and the groups receive different follow-up procedures. Treating them as interchangeable arms would ignore how participants were classified and measured. Clear reporting of participant flow and analysis populations is particularly important in such a design.
The outcome also depends on signal processing and classification of MRI components. The registry describes co-registration, independent component analysis, and evaluation for suspected seizure-onset zones, but does not report enough information to assess classification reliability or measurement repeatability. Statistical interpretation of a median depends on the underlying values and their variability, neither of which is reported for the primary outcome.
Finally, a pilot study can be informative about feasibility and measurement procedures, but the registry lists only selected secondary outcomes and does not report their results. Without outcome estimates and uncertainty, readers cannot distinguish a potentially meaningful pattern from noisy variation. The record’s lack of reported analyses makes transparent reporting of the eventual results especially important.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record reports enrollment of 5 and a terminated status, but does not report why the study was terminated or whether termination altered planned recruitment, treatment, scanning, or follow-up. The number of participants contributing to each outcome and the extent of completion are not reported. This makes it difficult to assess the available information behind any outcome, even though no primary results are posted.
The trial is open-label and non-randomized. Participants are classified according to seizure-network status, and the two groups have different intervention and follow-up procedures. The negative group therefore cannot serve as a direct control for the primary pre/post endpoint. The registry does not report an alternative strategy to address confounding or temporal change.
The primary outcome relies on an imaging-derived measure and component classification. Details about reproducibility, assessor agreement, blinding of image evaluation, and missing or uninterpretable scans are not reported in the registry record. The second scan may occur from 3 to 13 days after intervention start, so follow-up timing can vary; the record does not describe an analysis of timing differences.
The actual primary outcome values, uncertainty estimates, statistical tests, analysis populations, and missing-data methods are not reported. Neither are results for the listed secondary outcomes. The serious adverse-event counts are descriptive, and the registry does not report causal attribution. The reason for termination, the sample-size justification, and any interim analyses are also not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Antiseizure Medication in Seizure Networks at Early Acute Brain Injury — NCT06081283.
- Registry record last updated 2025-11-14; status last verified 2025-07.
- Results first posted 2025-11-14.
- 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.
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18. Record Summary
NCT06081283 is a Phase 4, open-label, non-randomized pilot with a sequential model, listed enrollment of 5, and status terminated. It concerns antiseizure medication and seizure-network connectivity in people with acute brain injury and suppression of consciousness. The registry describes pre- and post-intervention resting-state functional MRI for seizure-network-positive participants and no repeat scan or intervention for seizure-network-negative participants.
The primary outcome is the median seizure-network power-spectrum measure, with full range as the stated dispersion measure. The record reports no statistical analyses and no primary or secondary outcome results. Serious adverse-event and death counts are listed by group, but they do not establish causation or provide a randomized comparison. The reason for termination, analysis details, missing-data handling, and sample-size justification are not reported in the registry record.