Brivaracetam to Reduce Neuropathic Pain in Chronic SCI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Brivaracetam to Reduce Neuropathic Pain in Chronic SCI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial (NCT05639946), a randomized phase 3 study. The primary outcome is The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Average Worst Neuropathic Pain Intensity.

2. Clinical Question

3. Trial Design

The registry describes a Phase 3, randomized, parallel-group trial comparing brivaracetam with placebo. Its title identifies it as double-blind, while the masking field states triple masking. The registry does not specify which participant, investigator, or other roles were masked, so the practical details of the masking arrangement are not reported in the registry record.

The record lists enrollment as 44. The posted primary outcome results give group sizes of 21 in the experimental group and 19 in the control group. These are distinct registry entries with different purposes; the record does not explain the relationship between the enrollment figure and the group sizes in the results. The primary analysis population and reasons for any difference are not reported in the registry record.

The experimental intervention was brivaracetam, with individualized titration and a stated goal of 100mg BID. The control intervention was placebo. The registry describes a titration schedule of 50mg BID for 1 week followed by 100mg BID for 28 days as tolerated, and notes that participants could reduce the brivaracetam dose. Further operational details are not reported in the registry record.

The study is listed as completed. Its start date is 2023-01-01, and its primary completion date is 2024-10-07. The sponsor is the University of Minnesota. The record does not report the detailed protocol, randomization method, allocation concealment, or statistical 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

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.

Population: Baseline characteristics are only available for n=43 who proceeded to data collection after consenting, and before stopping/removed from the study. n=1 participant was found to not have met protocol eligibility after consenting and thus, did not complete any study activities.

6. Primary Endpoint

The registry lists the primary outcome as The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Average Worst Neuropathic Pain Intensity, measured over 7 Weeks Post Intervention.

The primary endpoint is change in average worst neuropathic pain intensity, measured using Version 2.0 of the International Spinal Cord Injury Pain Data Set (ISCIPBDS). The measure asks about average worst neuropathic pain intensity in the last week and uses a 0-10 numerical rating scale. Higher scores represent greater pain intensity.

The registry states that change is evaluated by comparing baseline intensity with intensity at 7 Weeks Post Intervention. A change measure can describe how scores differ between the measurement occasions, while a comparison between randomized groups addresses whether the recorded changes differed across the assigned interventions. The registry does not specify the exact arithmetic convention used to calculate change, so the sign should be read as reported rather than assigned a more specific interpretation.

Patient-reported pain intensity is relevant to the stated study question because the trial aims to assess neuropathic pain in people with spinal cord injury. The outcome is continuous: it summarizes pain on a numerical scale rather than counting events. A group mean describes the average reported change, while the standard deviation describes variation among the observations. Neither statistic alone describes every participant's experience.

7. Results Posted in the Registry

• Experimental Group: mean -0.50 versus -0.50 on control; difference 0.00 (95% CI -1.09 to 1.09), standardized effect d = 0.00; z-test p = 1.000.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result compares group means for a continuous outcome. The outcome is change in pain intensity, measured in points on a numerical rating scale. For such an endpoint, a mean summarizes the average recorded value in a group. A standard deviation summarizes how dispersed the recorded values are around that average. These are different summaries: the mean describes the group center, while the standard deviation describes variability among observations.

What does the mean difference represent?

A mean difference expresses the contrast between two group averages on the outcome's original scale. Here, the registry reports a mean difference of 0.0 points. Because the two posted group means are both -0.5 points, the reported contrast is centered at zero. The estimate is in points, so it can be interpreted on the same scale as the pain measure. The record does not give a clinically important difference threshold, so the estimate cannot be classified against such a threshold using the registry results.

How should the confidence interval be read?

A confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. The reported interval for the mean difference runs from -1.089 to 1.089 points. It includes zero, the value corresponding to no between-group difference, as well as values on either side. The interval is not a list of observed participant outcomes and is not a guarantee that the true effect lies inside it. Its interpretation depends on the analysis model and the validity of its assumptions. Details of the model and the method used to construct the interval are not reported in the registry record.

What does the p-value add?

The reported unadjusted p-value is 1.0. In general, a p-value evaluates how unusual data at least as extreme as those observed would be under a specified null hypothesis and analysis model. It does not give the probability that the treatment has no effect. It also does not indicate the clinical importance of the estimate. Because the record labels the value unadjusted, it should not be presented as a multiplicity-adjusted result. Whether any adjustment was planned or applied elsewhere is not reported in the registry record.

Why consider variation and assumptions?

The posted standard deviations are 2.0 points in the experimental group and 1.5 points in the control group. Variation affects how precisely group means and their contrast can be estimated. In general, analysis methods for continuous outcomes may rely on assumptions about the distribution of observations and the relationship between their variability and the model. If variability differs markedly across groups, or if observations depart substantially from model assumptions, some methods may give misleading uncertainty estimates. The registry record does not provide diagnostic checks or enough detail to assess those assumptions.

The trial is described as randomized and parallel-group. In general, random allocation aims to make groups comparable at baseline, on average, for factors that might affect the outcome. It does not ensure that every realized group is identical in all characteristics. The registry record does not report baseline values for this endpoint, adjustment variables, or the specific randomization procedures, so those features cannot be assessed from the posted results.

What are the planning illustrations?

Any sample-size figures associated with planning illustrations should be understood as hypothetical design calculations, not as observed power for this completed trial. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations depend on the selected assumptions and effect target. They do not show the probability that the completed trial detected an effect, and they are not the trial's original design justification. The trial's own sample-size justification is not reported in the registry record.

Overall, the primary comparison is interpretable as a continuous-outcome mean contrast, but the registry gives limited detail about the calculation methods, model checks, analysis population, and handling of incomplete outcome data. These omissions constrain evaluation of how robustly the displayed uncertainty reflects the trial's design and data.

10. Confidence Intervals and Precision

The mean-difference estimate is 0.0 points, and its reported 95% confidence interval extends from -1.089 to 1.089 points. This interval is the main indication of precision available for the primary comparison. It includes zero and permits differences in either direction under the reported analysis. It therefore supports neither a claim that the groups differed nor a claim that they were equivalent.

Precision concerns the uncertainty of an estimate, not whether an outcome is clinically important. A narrow interval can still include effects that matter to patients, while a wider interval can leave a broad range of effects compatible with the data. The registry record does not state a clinically important difference threshold, so the interval cannot be judged against such a threshold from the posted results.

The group means are both -0.5 points. The standard deviations are 2.0 points in the experimental group and 1.5 points in the control group. These figures help describe the outcome distribution, but they are not substitutes for the confidence interval around the between-group contrast. The record does not provide individual observations, a detailed interval calculation method, or sensitivity analyses that would clarify the effect of alternative assumptions.

A confidence interval is generally interpreted with reference to the model and sampling procedure used to construct it. The registry record does not report those technical details, so the interval can be quoted and its span described, but its assumptions cannot be independently evaluated from the record. It should not be read as a range containing a specified proportion of individual participants' changes.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures, but it does not post secondary outcome results in the results data described for this trial. The record also does not report a multiplicity strategy, such as a hierarchy of outcomes or an adjustment across multiple comparisons. The primary comparison's p-value is labeled unadjusted. It should therefore be read as the unadjusted value for that comparison, not as evidence that the broader family of trial questions has been controlled for multiple testing.

The study summary describes additional hypotheses involving parietal operculum connectivity measured by resting-state functional Magnetic Resonance Imaging and circulating miRNA-485. The registry record does not provide posted results for those hypotheses. Their findings cannot be inferred from the pain endpoint, and their absence from the posted results does not establish what the underlying measurements showed.

Missing-data procedures are not reported in the registry record. The record does not explain whether outcome data were missing, how any missing observations were handled, or whether sensitivity analyses were performed. It also does not identify the analysis population, such as whether the primary comparison included all randomized participants or a subset. The posted outcome group sizes are recorded, but they do not by themselves establish the analysis population or explain why those counts differ from the enrollment figure.

In general, missing outcome data can affect estimates when the probability of being observed is related to outcomes or participant characteristics. Different assumptions and methods can lead to different estimates. Without a reported missing-data approach, the reader cannot assess whether the comparison is robust to incomplete measurements. The statistical analysis plan, handling of protocol deviations, and any prespecified approach to multiplicity are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted safety figures report zero serious adverse events in the experimental group and zero in the control group. Deaths are also recorded as zero in both groups. For other adverse events, the record reports 15 affected participants in the experimental group and 9 in the control group. These are counts as recorded; they should not be converted into percentages or interpreted as event rates without additional information.

Zero recorded serious adverse events does not establish that serious events are impossible or that the interventions have identical safety profiles. It describes what was recorded for the groups and observation period represented in the registry. The record does not provide event-level descriptions for serious events, since no serious terms are listed, and it does not report detailed definitions, collection procedures, severity grading, or attribution to study treatment.

The other-adverse-event counts do not show how many events each affected participant experienced, how long participants were observed, or whether events differed in type or severity. The registry record also does not provide a statistical comparison of safety outcomes. These figures are descriptive and should be interpreted separately from the primary pain endpoint.

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

The posted primary result is an estimated mean difference of 0.0 points in change in average worst neuropathic pain intensity, with a 95% confidence interval from -1.089 to 1.089 points and an unadjusted p-value of 1.0. The two group means are both -0.5 points. These results describe the recorded comparison at 7 Weeks Post Intervention, on the endpoint and scale specified in the registry.

The result does not establish that the true treatment effect is exactly zero. The confidence interval includes zero and values in either direction. Nor does it demonstrate equivalence or non-inferiority: those conclusions require a prespecified framework and margin, which are not reported in the registry record. A p-value of 1.0 is not the probability that there is no effect and does not answer whether a difference would be important to participants.

The registry record does not report a clinical importance threshold for this pain scale, so it is not possible to conclude from these statistics alone whether the interval excludes differences that would matter to patients. The result also cannot be generalized automatically to other pain outcomes, other time points, or populations not described in the record. Secondary results and the analysis population are not reported in the registry record.

The trial summary includes hypotheses about brain connectivity and circulating miRNA-485, but the posted primary result is a pain-intensity comparison. The pain result cannot confirm or refute those other hypotheses. Similarly, the listed adverse-event counts are descriptive and do not replace a complete safety analysis.

Overall, the registry result gives a point estimate at zero and an interval that remains compatible with differences on either side. The appropriate statistical conclusion is bounded by that estimate, its uncertainty, and the limited analysis details available in the registry record.

14. Why This Trial Matters Statistically

This trial raises a clear statistical question: how precisely does the observed difference between brivaracetam and placebo estimate a change in neuropathic pain intensity among people with chronic spinal cord injury? Reporting both group means and a between-group confidence interval makes it possible to distinguish the estimated contrast from the variation within each group. The point estimate alone would not communicate the uncertainty represented by the interval.

The result also illustrates why a p-value should not be treated as a complete summary. The reported unadjusted p-value is 1.0, but interpretation also requires the estimated difference and its interval. The interval includes zero and values on both sides, and the registry does not provide a clinical importance threshold. Statistical evidence, precision, and clinical meaning are related but distinct questions.

There are further statistical questions that the registry record leaves open. It does not report the analysis population, missing-data method, multiplicity plan, detailed model, or sample-size justification. These details matter when assessing whether the uncertainty estimate matches the intended design and whether the primary comparison can be interpreted as prespecified. The posted sample-size illustrations, if considered, are planning calculations based on stated assumptions and the observed effect; they are not observed power and are not the trial's design rationale.

Finally, the study summary describes biological and imaging hypotheses beyond the primary pain outcome. Separating those hypotheses from the posted primary comparison helps prevent an outcome on one measure from being treated as evidence about another. The record therefore offers a focused estimate while leaving important questions about analysis procedures and secondary outcomes unresolved.

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 registry record offers limited detail for evaluating the primary analysis. It does not report the statistical analysis plan, the precise model used to estimate the mean difference, model diagnostics, or whether any covariate adjustment was applied. The confidence interval and unadjusted p-value can be described as posted, but the assumptions and analytic choices behind them cannot be fully reviewed from the record.

The record lists enrollment as 44, while the primary results list group sizes of 21 and 19. It does not explain the relationship between these figures, identify the primary analysis population, or give reasons for any difference. Missing-data status and handling are also not reported. These omissions prevent assessment of whether incomplete outcomes or exclusions may have influenced the estimate.

The registry identifies 10 outcome measures, but does not provide secondary outcome results in the posted results data described for the trial. It does not state a multiplicity procedure or a clinical importance threshold for the primary pain measure. The record therefore does not support conclusions about secondary hypotheses, adjustment across outcomes, or the practical importance of the interval.

The endpoint description specifies the scale and timing but does not state the arithmetic convention used to define change. The trial is described as triple-masked, but the roles covered by masking are not specified. Details of allocation concealment, treatment adherence, and follow-up completeness are also not reported in the registry record. These limitations concern the information available in the record and do not establish that the underlying trial lacked these procedures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Brivaracetam to Reduce Neuropathic Pain in Chronic SCI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial — NCT05639946.
• Registry record last updated 2026-03-18; status last verified 2026-02.
• Results first posted 2026-03-18.
• 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

The registry describes a completed, randomized, parallel-group Phase 3 trial of brivaracetam versus placebo for neuropathic pain in chronic spinal cord injury. Its title calls the study double-blind, and its masking field states triple masking. The sponsor is the University of Minnesota. The record lists enrollment as 44 and identifies the primary time point as 7 Weeks Post Intervention.

The primary outcome is change in average worst neuropathic pain intensity on the 0-10 ISCIPBDS Version 2.0 scale. The posted group means are -0.5 points in each group. The mean difference is 0.0 points, with a 95% confidence interval from -1.089 to 1.089 and an unadjusted p-value of 1.0.

The registry records zero serious adverse events and zero deaths in both groups, alongside other adverse-event counts of 15 and 9. Analysis-population details, missing-data methods, multiplicity procedures, and secondary results are not reported in the registry record.