Prospective Analysis of the Use of N-Acetylcysteine and Vitamins in the Treatment of TBI in Geriatric Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prospective Analysis of the Use of N-Acetylcysteine and Vitamins in the Treatment of TBI in Geriatric Patients (NCT04291066), a randomized phase 2 study. The primary outcome is Determine Improvement in Somatic, Cognitive, and Emotional Post-concussion Symptoms as Measured by the Rivermeade Post-concussion Questionnaire (RPQ) in Treatment Group vs Non-treatment Group..

2. Clinical Question

This is a question about symptom scores over the early post-injury period, not a single binary outcome such as symptom presence or absence. The RPQ scale ranges from 0 to 64, and higher scores indicate more severe symptoms. The registered primary measure is the median score with an inter-quartile range. Those summaries can describe the middle of each group’s score distribution and its spread, but they do not, by themselves, establish whether groups differ or whether any difference is statistically precise.

The record identifies traumatic brain injury as the condition and describes a geriatric population, but it does not provide further eligibility rules or describe how the population was characterized for the primary analysis. Without the posted scores, group comparisons, and analysis details, the clinical question is identifiable from the registration but cannot be answered from the registered outcome information.

3. Trial Design

The registry describes a randomized, parallel-group Phase 2 trial with no masking. Participants were assigned to a treatment group or a non-treatment group. In a parallel design, the assigned groups are followed as separate groups rather than participants crossing from one intervention to the other. Random allocation can help make groups comparable on average, although it does not guarantee balance in every characteristic, especially in an individual trial.

The treatment arm received oral N-acetyl cysteine and oral multivitamin tablets. The comparator was routine care. The registry does not describe the components of routine care, whether the treatment was added to routine care, or how adherence was assessed. Masking is recorded as none, so the trial was open-label according to the registry. The record does not state whether outcome assessors were masked or describe procedures intended to reduce bias in symptom reporting or assessment.

The registry lists an enrollment of 92. The adverse-event record lists 46 participants at risk in each group, but those safety counts do not establish the analysis population for the primary outcome. Enrollment, numbers assessed at each follow-up, and numbers included in each outcome analysis can differ; follow-up and analysis counts for the RPQ are not reported in the registry record.

The study is marked completed. Its listed start date is 2019-09-01 and its primary completion date is 2020-04-30. These dates describe the registry record’s study timeline; they do not give the timing or completeness of individual participants’ follow-up. The primary outcome timeframe is 0 to 30 days after the traumatic brain injury event. The record also names Glasgow Coma Scale (GCS) at arrival and discharge as a secondary outcome, but does not provide its results.

Although the design is described as randomized, the method used to generate or conceal the allocation sequence is not reported in the registry record. The record does not specify whether allocation was stratified, how participants were recruited, or how withdrawals and protocol deviations were handled. Those details matter when judging how the trial was conducted, but cannot be inferred from the design labels alone.

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 Determine Improvement in Somatic, Cognitive, and Emotional Post-concussion Symptoms as Measured by the Rivermeade Post-concussion Questionnaire (RPQ) in Treatment Group vs Non-treatment Group., measured over 0 to 30 days post traumatic brain injury event.

The primary endpoint is the Rivermead Post-concussion Questionnaire (RPQ) score, used to assess somatic, cognitive, and emotional post-concussion symptoms. The registry describes scores at three post-injury assessments: within 24 hours of admission (Day 0), Day 7, and Day 30. The stated timeframe is 0 to 30 days after the traumatic brain injury event.

The listed RPQ scale ranges from 0 to 64. Each item is described on a scale from 0, meaning not experienced at all, through 1, no more of a problem, 2, a mild problem, 3, a moderate problem, and 4, a severe problem. Higher total scores indicate more severe symptoms. Repeated measurements can describe symptom status at different points in the early recovery period; they should not be treated as interchangeable assessments or collapsed into one result without an analysis rule.

The registry specifies the median and inter-quartile range as the outcome summary. The median is the middle value in an ordered set of scores; the inter-quartile range describes the spread of the central portion of that set. These summaries can be useful when scores are not well represented by a mean and standard deviation. They do not show the full score distribution or quantify uncertainty around a between-group contrast unless an inferential analysis is also reported.

The registry does not report RPQ values, a treatment-group comparison, or the method used to analyze the repeated measurements. It therefore does not show whether symptom scores changed over time or how precisely any group difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, unmasked, and parallel-group. These are design descriptors rather than a complete statistical analysis plan. Randomization is generally used to reduce systematic differences between treatment groups at assignment. In a parallel-group trial, each participant remains in the assigned group for the comparison. With no masking recorded, participants and study personnel may have known group assignment; the registry does not clarify whether outcome assessors were masked.

What does the registered summary measure?

The primary endpoint is summarized using the median and inter-quartile range. In general, a median is the central observation after values are ordered, while the inter-quartile range describes the spread of the central half of the observations. These summaries can be informative for symptom scores whose distributions are skewed or contain unusually high or low values. They do not reveal every feature of a distribution, and they do not themselves estimate the uncertainty in a treatment contrast.

The RPQ is recorded at Day 0, Day 7, and Day 30 after injury. Repeated measurements from the same participant are related: a participant’s scores over time are not independent observations. An analysis that compares patterns over time should account for that within-participant relationship. The registry does not report whether the analysis used a repeated-measures model, separate comparisons at each assessment, or another method. It also does not state which time point or contrast was intended to be the primary test.

Why does the endpoint definition matter?

The scale ranges from 0 to 64, with higher scores indicating more severe symptoms. A statistical comparison should preserve that direction when describing any group contrast. A lower score would represent fewer or less severe reported symptoms on this scale, but the registry contains no observed group scores from which to describe such a contrast. The item-level response descriptions do not establish a threshold for clinically meaningful change; that threshold is not reported in the registry record.

The registry title for the primary outcome refers to improvement in the treatment group versus the non-treatment group. The measurement description lists scores at three times, but does not define whether improvement means change from Day 0, a difference between groups at a later assessment, or a difference in trajectories. These are distinct estimands: they answer different questions and can yield different interpretations. No specific estimand or model is reported.

What can confidence intervals and p-values tell readers?

In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. For a treatment comparison, it can communicate both the direction and range of values compatible with the observed data and model. A p-value assesses how compatible the data are with a specified null hypothesis under the analysis assumptions; it does not measure the size or clinical importance of an effect. Neither is reported for the primary outcome in the registry record, so neither can be interpreted for this trial’s main question.

General statistical caution applies when several time points or outcomes are examined. Repeated testing can increase the chance of an apparently notable result arising by chance if tests are treated as independent opportunities to claim a finding. Appropriate interpretation depends on which comparisons were prespecified and whether any multiplicity strategy was planned. The registry does not report a multiplicity plan, primary contrast, or inferential results, so there is no basis to characterize how multiplicity was handled.

How should the planning illustration be read?

The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. It specifies that the target effect is a stated fraction of the observed effect. Such calculations illustrate what sample size might be needed under their assumptions; they do not show the power actually achieved by the completed trial. They are also not evidence that the trial was originally designed using those assumptions. The original sample-size justification is not reported in the registry record.

The planning assumptions do not resolve the missing primary analysis. A sample-size illustration is meaningful only in relation to a specified outcome contrast, variability assumptions, and analysis. The record does not provide a primary-outcome effect estimate or the analysis details needed to evaluate those inputs. No planning count should be interpreted as an observed result or as a substitute for a confidence interval around the trial’s actual comparison.

What remains unspecified?

The registry does not report the statistical test or model for the primary endpoint, how missing measurements were handled, or which participants were included in the analysis. It does not describe adjustments for baseline scores or other covariates. These choices can affect estimates and uncertainty. General methods such as baseline adjustment or repeated-measures modeling may be appropriate in some settings, but there is no basis to say that this trial used them.

The record lists GCS at arrival and discharge as a secondary outcome but does not provide its analysis or results. It lists two outcome measures and no analyses. The meaning and handling of the additional measure, including any multiplicity considerations, are not described. The statistical information available therefore supports interpretation of the design and endpoint definition, but not a reconstruction of the analysis or a conclusion about the treatment comparison.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is assessed at Day 0, Day 7, and Day 30, and the record also names GCS at arrival and discharge as a secondary outcome. Multiple assessments create choices about which comparison is primary and how results across time points and outcomes should be interpreted. The registry does not report a multiplicity strategy, such as a hierarchy of tests or an adjustment procedure. It also does not identify one time point or contrast as the sole inferential comparison.

Missing data are important for a repeated symptom measure because participants may not have a score at every assessment. The registry does not report the number of RPQ observations at each time, reasons for missing assessments, or how missing values were handled. It does not describe whether analyses used all available measurements, imputed missing values, or restricted analysis to participants with complete data. These approaches rely on different assumptions and may produce different estimates.

The analysis population is also not specified. The registry gives an enrollment of 92 and safety records with 46 participants at risk in each group, but it does not state which participants were included in the primary-outcome analysis or whether participants were analyzed according to randomized assignment. The number enrolled should not be assumed to equal the number assessed or analyzed at each follow-up.

Without the analysis population, missing-data methods, prespecified primary contrast, and multiplicity plan, the completeness and confirmatory status of any outcome comparison cannot be assessed. These details are not reported in the registry record.

11. 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 serious adverse event terms

Serious events with the highest arm-level rate: death (10.9%).

The registry’s adverse-event record lists 46 participants at risk in each group. Serious adverse events are recorded for 2 participants in the treatment group and 7 in the non-treatment group. Other adverse events are recorded for 0 participants in each group. The record lists deaths as 2 in the treatment group and 7 in the non-treatment group, and identifies Death at 10.9% among the top serious terms.

These are registry-reported counts, not a causal comparison. The record does not report the event observation period, whether events were independently adjudicated, or the circumstances and timing of the deaths. The denominator used for the listed 10.9% is not reported in the registry record. The record also does not provide a statistical comparison or uncertainty interval for these safety figures.

Serious adverse-event counts and deaths should be read separately from the RPQ symptom outcome. They do not show whether symptom scores differed, and the registry information does not establish why an event occurred or whether it was related to the intervention. The counts describe what is recorded, not a complete assessment of safety or a treatment effect.

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

The registry record establishes that a randomized, parallel-group Phase 2 trial compared oral N-acetyl cysteine and oral multivitamin tablets with routine care in geriatric patients after traumatic brain injury. It identifies the RPQ as the primary symptom measure and specifies assessments from Day 0 through Day 30. Those details explain the clinical question the trial was intended to address.

The record does not report the primary outcome values or an analysis comparing the groups. It therefore does not show whether the groups’ RPQ scores differed, whether scores changed differently over time, or how precise any estimated difference was. No conclusion that the intervention improved symptoms, had no effect, or produced equivalent outcomes can be drawn from the registered primary-outcome information.

A missing result in the registry is not the same as a result showing no difference. Likewise, the study’s completed status does not demonstrate that outcome data were analyzed or posted. The number enrolled and the safety counts do not fill that gap, because they do not provide the missing symptom scores or their analysis.

The adverse-event record does describe serious events and deaths in both groups, but it lacks information needed to interpret causes, timing, and statistical uncertainty. Those figures should not be used as a substitute for a full safety analysis or combined with the symptom endpoint to infer an overall treatment effect.

In general, a sound interpretation of a randomized trial depends on the estimated comparison, its uncertainty, the analysis population, and the methods used to handle repeated measurements and missing data. Those elements are not reported for the primary outcome in this record. The defensible conclusion is limited: the registered question and design are described, but the posted registry information does not answer the question about post-concussion symptoms.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary endpoint is a symptom score measured repeatedly during an early post-injury period. Repeated measures can provide information about the course of symptoms, but they require a clear definition of the comparison: a group difference at a particular assessment, change from an initial assessment, or a difference in patterns over time. The registry names multiple assessments without specifying which contrast was intended for the primary analysis.

The choice to report medians and inter-quartile ranges indicates that the planned descriptive summary focuses on the center and spread of score distributions. That choice can be useful for symptom data, but descriptive summaries alone do not quantify a treatment contrast or its precision. A reported inferential analysis would be needed to support those interpretations.

The design also draws attention to the difference between a randomized label and a fully documented analysis. Randomization is intended to support a fair comparison, but assessment completeness, allocation procedures, outcome ascertainment, and analysis choices remain important. Here, masking is recorded as none, while details about outcome assessment and the analysis population are not reported.

Finally, the registry includes a sample-size planning illustration, but such a calculation is not the same as an original design justification or the power observed in the completed trial. Without the primary results and analysis methods, neither the planning illustration nor the enrollment figure can establish what the trial found. The statistical importance of the record is therefore as much about identifying the unanswered analysis questions as it is about documenting the trial design.

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 principal limitation for interpreting this trial from the registry is that the primary-outcome results and analysis are not reported. The registry defines the RPQ endpoint and its assessment times, but does not provide group scores, a treatment contrast, or an estimate of uncertainty. The intended question therefore cannot be answered using the recorded primary-outcome information.

The primary endpoint involves multiple assessments, but the record does not specify the primary time point or contrast. It does not state how repeated measurements were modeled or whether the analysis focused on change from Day 0, later scores, or the overall pattern. The record also does not report a threshold for clinically meaningful change, so statistical differences, if available elsewhere, could not be interpreted against a registry-defined threshold.

Further limitations include the absence of information about missing RPQ assessments, reasons for loss to follow-up, and the primary analysis population. The method of random sequence generation and allocation concealment is not reported. Although masking is listed as none, the registry does not describe who assessed outcomes or whether any assessors were masked. Details of routine care and adherence to the treatment are also not reported.

The safety record lists serious adverse events and deaths but does not give their timing, causes, observation period, or an inferential comparison. The listed percentage for Death has no reported denominator. These omissions limit interpretation of safety counts and prevent causal conclusions from the registry record alone.

Finally, the registry provides no reported analyses and does not describe a multiplicity plan despite multiple outcome assessments. The record’s completed status and enrollment figure do not resolve these uncertainties.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Prospective Analysis of the Use of N-Acetylcysteine and Vitamins in the Treatment of TBI in Geriatric Patients — NCT04291066.
• Registry record last updated 2026-05-01; status last verified 2025-01.
• Results first posted 2026-05-01.
• 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.

18. Record Summary

The registry describes NCT04291066, a completed randomized, unmasked, parallel-group Phase 2 trial sponsored by HonorHealth Research Institute. It lists enrollment of 92 and compares oral N-acetyl cysteine plus oral multivitamin tablets with routine care in geriatric patients who experienced traumatic brain injury.

The primary outcome is the RPQ score, summarized by median and inter-quartile range at Day 0, Day 7, and Day 30 after injury. Higher scores on the 0 to 64 scale indicate more severe symptoms. GCS at arrival and discharge is listed as a secondary outcome. The registry does not report analyses or results for the primary outcome.

The adverse-event record lists serious adverse events in both groups and deaths in both groups, but does not provide the detail needed to infer cause or treatment effect. The registry also does not report the primary analysis population, handling of missing data, or multiplicity approach.