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 Prazosin and Cerebrospinal Fluid (CSF) Biomarkers in Mild Traumatic Brain Injury (mTBI) (NCT03221751), a randomized phase 4 study. The primary outcome is Change in CSF Total-tau From Baseline to End of Study (pg/mL).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03221751 |
| Phase | Phase 4 |
| Condition | Dementia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 9 |
| Arms in the primary outcome | 2 |
| Lead sponsor | VA Office of Research and Development |
| Results posted | Yes |
2. Clinical Question
Population
Veterans who experienced mild traumatic brain injuries were the intended population described in the registry summary. The registry lists dementia as the condition and records total enrollment as 9. The primary endpoint information is much more limited: it records one placebo participant with a result and notes that the one prazosin participant did not have a lumbar puncture at the study termination visit.
Intervention
The intervention was prazosin hydrochloride. Participants were to be titrated according to a dosing algorithm to the maximum dose or maximum tolerated dose. The stated maximum was 5 mg in the morning, 5 mg in the afternoon, and 15 mg at bedtime.
Comparator
The comparator was placebo. Its arm description gives the same titration language and stated maximum dose as the prazosin description. The registry identifies the study as randomized, triple-masked, and parallel-group, but the specific randomization procedure and the people included in masking are not reported in the registry record.
Primary question
The primary question was whether prazosin changed cerebrospinal-fluid (CSF) total-tau from baseline to the end of the study, with the endpoint assessed over 10 weeks. Total-tau is described in the registry as an established biomarker of neurodegeneration in Alzheimer's disease. The study rationale was to assess whether prazosin might increase removal of tau and beta amyloid from the brain, using CSF concentrations as the measurement. The posted primary endpoint information does not permit a comparison between treatment arms.
3. Trial Design
The registry describes a Phase 4, randomized, triple-masked, parallel-group trial sponsored by the VA Office of Research and Development. It records enrollment of 9 and status as terminated. The recorded study dates are a start date of 2016-12-01 and primary completion date of 2023-01-03. The registry does not state why the trial was terminated.
Participants were assigned to prazosin hydrochloride or placebo. Both arm descriptions specify titration to a maximum or maximum tolerated dose according to a dosing algorithm. The maximum dose listed is 5 mg in the morning, 5 mg in the afternoon, and 15 mg at bedtime. Further details about the titration algorithm, treatment duration, adherence, and actual doses taken are not reported in the registry record.
The primary endpoint was change in CSF total-tau from baseline to the end of study, with a 10-week timeframe. Although the overall enrollment is 9, the posted primary endpoint result includes only one participant in the placebo arm and no participants in the prazosin arm. The registry's population note says the one prazosin participant did not have a lumbar puncture at the study termination visit. The record does not explain the disposition or endpoint availability of the other enrolled participants.
The trial has 3 outcome measures listed, but no secondary results are posted. The registry reports no analyses. It does not report the randomization method, masking roles, planned analysis population, sample-size justification, or full statistical analysis plan. These omissions limit how far the design and reported endpoint data can be evaluated.
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
| Stage | Prazosin | Placebo |
|---|---|---|
| STARTED | 1 | 1 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Prazosin | Placebo |
|---|---|---|
| lumbar puncture not performed at early termination. | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The one prazosin participant did not under a lumbar puncture at the study termination visit.
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 | Prazosin | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 1 | 2 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 1 | 2 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 52 (52 to 52) | 39 (39 to 39) | 45.5 (39 to 52) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Change in CSF Total-tau From Baseline to End of Study (pg/mL), measured over 10 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | pg/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in CSF total-tau from baseline to the end of the study, measured in pg/mL over 10 weeks. Total-tau is a protein measured in cerebrospinal fluid, the fluid surrounding the brain and spinal cord. The registry describes it as an established biomarker of neurodegeneration in Alzheimer's disease. The study rationale links CSF biomarker levels to the question of whether prazosin might increase removal of tau and beta amyloid from the brain.
A change endpoint compares a participant's measurement at the end of the study with that participant's baseline measurement. This can describe movement over the treatment period, but a comparison between randomized groups is needed to distinguish a treatment-group pattern from changes that might occur over time for other reasons. That comparison cannot be made from the posted primary results: the placebo arm has one recorded result, 11.0 pg/mL, and the prazosin arm has no recorded endpoint value.
The registry does not give dispersion, a confidence interval, or a statistical test for this endpoint. It also does not report baseline values or explain further how the posted value is defined beyond the endpoint title. The single posted number therefore cannot describe the range of participant changes or establish a precise between-arm estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary endpoint result is 11.0 pg/mL for the placebo arm, based on 1 participant. The prazosin arm has no reported primary endpoint value, and the registry notes that its one participant did not have a lumbar puncture at the study termination visit. Because there is no endpoint result for the prazosin arm, the registry results do not provide a treatment-versus-placebo estimate for change in CSF total-tau.
This is not merely a case of a comparison that is imprecise but otherwise quantifiable. The two-arm comparison is not estimable from the posted results. There is no reported difference between arms, uncertainty interval, or p-value. A single placebo result also cannot show how much individual values varied within that arm. The value of 11.0 pg/mL should be read as a single-arm observation, not as evidence of a pattern among participants or as a comparative treatment effect.
The registry records 9 participants enrolled overall, but that total should not be mistaken for the number contributing to this endpoint. The endpoint information lists 1 participant in the placebo arm and 0 in the prazosin arm. The record does not report why the other enrolled participants lack posted endpoint values, whether they had baseline measurements, or whether their data were excluded from the analysis. It also does not describe an analysis population or missing-data procedure.
In general, confidence intervals express the range of values compatible with an estimate under the assumptions of the statistical method. No confidence interval is reported for this endpoint, and the available arm information does not support a two-arm interval. Likewise, a p-value would address compatibility of data with a specified null model; no such test is posted. The absence of a test is not evidence that the groups were equivalent, and it does not establish that there was no treatment effect.
The record lists 3 outcome measures, but it posts no secondary results and no analyses. Consequently, there is no additional reported endpoint evidence that can resolve the missing primary comparison. The trial's terminated status is also relevant to the completeness of the record, but the reason for termination is not reported. The registry evidence supports a narrow description of what was posted: one placebo participant's primary endpoint value, no prazosin endpoint value, and no estimable arm comparison. Broader conclusions about the study's intended population or the drug's effects are not supported by these results.
9. Statistical Methods Explained
What does a change endpoint represent?
In general, a change endpoint is calculated by comparing a participant's measurement at a later time with that participant's baseline measurement. It focuses on within-person movement during the study period. A randomized comparison then asks whether the pattern of changes differs between the intervention and comparator groups. The endpoint title identifies change in CSF total-tau from baseline to the end of study, and the registry gives a 10-week timeframe. It does not provide further detail on the exact calculation or handling of baseline values.
The posted data do not support a comparison of change between groups. The placebo arm has 1 participant and a value of 11.0 pg/mL; the prazosin arm has 0 participants with a reported value. A treatment contrast requires endpoint information from both groups. It would not be appropriate to fill the absent arm result using the placebo value or any other assumption.
Why do estimates need uncertainty measures?
General statistical interpretation distinguishes an estimated effect from its uncertainty. A point estimate gives a single summary of a comparison, while a confidence interval communicates uncertainty around that estimate under the analysis assumptions. A p-value is another inferential summary, interpreted in relation to a specified statistical model and null hypothesis. None of these comparative statistics is reported for the primary endpoint. Since the prazosin endpoint value is missing, the registry's posted results do not permit a direct two-arm estimate to which an uncertainty measure could be attached.
With only one posted placebo observation, there is also no reported estimate of within-arm spread. Such spread describes how much participant results vary, and it is distinct from uncertainty about a group mean or treatment contrast. The record gives no dispersion measure for the primary endpoint. This makes it especially important not to treat the single result as representative of the placebo arm.
What does the design tell the reader?
Randomization is intended, in general, to create comparable groups by assigning participants according to chance rather than by clinical judgment. Triple masking generally means that three categories of people involved in a trial are kept unaware of assignment, but the registry does not identify which people were masked or explain the masking procedures. A parallel design assigns participants to a group that is followed as a separate arm rather than describing a crossover. These labels convey the broad design, but do not supply operational details.
The registry identifies the trial as Phase 4 and gives the total enrollment as 9. Its primary completion date is 2023-01-03, and its status is terminated. The record does not state the reason for termination, the planned sample size, or the justification for that target. It does not report an interim-analysis plan, stopping rules, or a full statistical analysis plan. These details cannot be inferred from the design labels or from the enrollment total.
How should sample-size planning be separated from observed evidence?
General sample-size planning asks how many participants would be needed to detect a chosen effect under assumptions about variability, significance level, allocation, and statistical model. A planning calculation is conditional on those assumptions; it is not a result observed in the trial and does not show what the study actually had power to detect. The registry record does not report a sample-size justification or a planned target beyond the overall enrollment entry. No numerical planning estimate is reported in the registry record.
Even a hypothetical planning exercise based on an observed effect would be difficult to interpret when the primary endpoint comparison is not estimable. The posted result is one placebo observation, with no prazosin observation and no reported dispersion. An effect derived from those data would not be a reliable estimate of a treatment contrast. No such recalculated comparison is reported, and no planning illustration should be mistaken for evidence from participants.
What does over-dispersion mean in general?
In general, over-dispersion occurs when outcome variability is greater than assumed by a statistical model. When that happens, standard errors and resulting uncertainty intervals can be too small if the model does not account for the extra variation. This concept is not a reported feature of this trial's analysis: the registry gives no dispersion estimate and no statistical model for the primary endpoint. With only one posted value in one arm and no value in the other, over-dispersion cannot be assessed from the registry results.
What can be inferred from the adverse-event summaries?
Safety summaries are counts within the groups at risk, not estimates of a comparative treatment effect. The record lists 1 participant at risk in each arm for serious adverse events and reports 0 serious events in each. It lists 1 participant at risk in each arm for other adverse events and reports 1 in each. There are 0 deaths in each arm. These counts do not include enough information to characterize event types, timing, severity, or causal attribution. In particular, equal counts in groups this small do not establish equivalent safety profiles.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures, but it posts no secondary outcome results. It reports no analyses. The primary endpoint is change in CSF total-tau from baseline to the end of study; the results list 1 participant and a value of 11.0 pg/mL in the placebo arm, and 0 participants with a reported value in the prazosin arm. The registry notes that the one prazosin participant did not have a lumbar puncture at the study termination visit.
Multiplicity refers, in general, to the statistical issue that arises when multiple outcomes, comparisons, time points, or analyses are tested. If many tests are considered, the chance of at least one apparently notable result can increase unless the analysis plan accounts for that. The registry record does not report a multiplicity strategy, a hierarchy of endpoints, or an analysis plan. Since no secondary findings are posted, there is no basis to evaluate how multiple outcomes were analyzed or interpreted.
The available information indicates missing primary endpoint data in the prazosin arm, but the reasons for missing data across the full enrollment are not reported in the registry record. The registry does not state whether missing values were imputed, whether participants were excluded, or whether sensitivity analyses were performed. It does not identify an intention-to-treat, per-protocol, or other analysis population. The one participant's absent lumbar puncture is therefore a documented reason for no termination-visit specimen in that case, but it does not explain endpoint availability for all enrolled participants.
Missingness matters because an analysis restricted to participants with observed measurements can differ from the result that would have been obtained had all randomized participants contributed data. General methods for handling missing outcomes rely on assumptions; the method and assumptions used in this trial are not reported. With no prazosin endpoint result and no reported missing-data analysis, the primary between-arm effect cannot be estimated from the posted results.
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 |
|---|---|---|---|
| Prazosin | 0 | 1 | 0.0% |
| Placebo | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Prazosin | 0 of 1 |
| Placebo | 0 of 1 |
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 |
|---|---|
| Prazosin | 1 of 1 |
| Placebo | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Prazosin | Placebo |
|---|---|---|---|
| adrenal insufficiency | Endocrine disorders | 0 of 1 | 1 of 1 |
| depressed mood | Psychiatric disorders | 1 of 1 | 0 of 1 |
| headache | General disorders | 1 of 1 | 0 of 1 |
| insomnia | General disorders | 1 of 1 | 0 of 1 |
| lack of energy | General disorders | 1 of 1 | 0 of 1 |
| lightheadedness | General disorders | 1 of 1 | 0 of 1 |
| nasal congestion | General disorders | 1 of 1 | 0 of 1 |
| pain from root canal | General disorders | 0 of 1 | 1 of 1 |
| weakness | General disorders | 0 of 1 | 1 of 1 |
The registry's adverse-event summary lists 1 participant at risk for serious adverse events in each arm. It reports 0 serious adverse events in the prazosin group and 0 in the placebo group. For other adverse events, it lists 1 participant at risk in each arm and reports 1 affected participant in each group. It reports 0 deaths in each arm. No serious adverse-event terms are listed.
These are small counts and should be read as counts, not as stable estimates of risk. In general, a count from a very small group offers little information about how often an event might occur in a broader population. The record does not provide descriptions of the other adverse events, their severity, timing, duration, or whether investigators considered them related to study treatment. It also does not provide additional detail on the adverse-event collection process.
The equal counts for other adverse events do not show that the arms had equivalent safety outcomes. The absence of reported serious events and deaths in these groups likewise does not establish that such events cannot occur. The summary supports only the narrow statement that the registry lists the counts above among the participants at risk.
12. What the Result Does, and Does Not, Mean
The result supports a limited account of the primary endpoint record: one placebo participant has a posted value of 11.0 pg/mL for change in CSF total-tau, while the prazosin arm has no posted value. The registry notes that the one prazosin participant did not have a lumbar puncture at the study termination visit. These data do not yield a treatment-versus-placebo estimate.
The number 11.0 pg/mL should not be interpreted as a typical placebo response or as a comparative effect. It is an observation from a single participant. There is no accompanying measure of variability, no confidence interval, and no reported statistical test. The record also does not describe the baseline and termination measurements underlying the change value in more detail.
The trial's rationale concerns whether prazosin might affect removal of tau and beta amyloid from the brain, assessed through CSF biomarkers. The primary endpoint focuses on total-tau; no primary result for the prazosin arm is posted, and no secondary results are posted. Therefore, the registry results do not establish whether treatment changed total-tau relative to placebo, and they do not establish effects on beta amyloid, chronic traumatic encephalopathy, Alzheimer's disease, or clinical symptoms.
Nor does the missing comparison establish that there was no effect. A lack of an estimable comparison is different from an estimate near zero with adequate precision. The registry does not report a reason for termination or the statistical plan, so those details cannot clarify why the endpoint results are incomplete. Interpretation should remain confined to what the record reports rather than extending the single observation to other participants or outcomes.
13. Why This Trial Matters Statistically
This record illustrates the distinction between a trial's design and the evidence that can be interpreted from its posted results. The study is described as randomized, triple-masked, and parallel-group, with prazosin and placebo arms. Those design features describe the intended comparison, but they do not ensure that a comparative estimate can be calculated when endpoint information is absent from one arm.
The contrast between 9 participants enrolled overall and the primary endpoint information for only 1 placebo participant and 0 prazosin participants is central to statistical interpretation. Enrollment is not the same as the analysis population for a particular endpoint. Without a reported account of participant flow, missing data, and analysis populations, readers cannot determine why only one value appears or how the endpoint results relate to all enrolled participants.
Statistically, a single observed value cannot characterize the distribution of outcomes in its group. And without a value in the other group, the treatment contrast is not estimable. The limitation is therefore not simply that uncertainty is wide; the needed comparative information is not posted. This is an important distinction when reading registry results, because an unavailable estimate cannot be interpreted as a null finding.
The record also shows why outcome reporting and analysis details matter. Three outcomes are listed, but no secondary results or analyses are reported. The statistical plan, missing-data procedures, and reason for termination are not reported in the registry record. These omissions constrain assessment of multiplicity, selection of analyses, and the completeness of results. The posted material can describe the study's objective and a small number of outcome and safety counts, but it cannot answer the primary comparative question.
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 most direct limitation is the absence of a reported primary endpoint value for the prazosin arm. The placebo arm has 1 participant with a reported value of 11.0 pg/mL, whereas the prazosin arm has 0. The registry notes that the one prazosin participant did not have a lumbar puncture at the study termination visit. A between-arm comparison cannot be estimated from this information.
The overall enrollment is 9, but the registry does not explain the endpoint status of the other enrolled participants. Participant flow, reasons for missing measurements, baseline endpoint data, and the definition of the analysis population are not reported. The record also does not state whether any missing-data method or sensitivity analysis was used. These gaps prevent assessment of how representative the one posted endpoint observation is of the trial participants.
No dispersion measure, confidence interval, or inferential test is reported for the primary endpoint. No secondary results or analyses are posted despite 3 listed outcome measures. The statistical analysis plan, multiplicity approach, and sample-size justification are not reported in the registry record. The reason the trial was terminated is also not reported.
Finally, the registry's safety summary is limited to counts among 1 participant at risk in each arm and does not describe the other adverse events. It does not report event timing, severity, or attribution. These reporting limitations do not establish that unreported analyses or events did or did not occur; they mean that the registry record does not provide that information for interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Prazosin and Cerebrospinal Fluid (CSF) Biomarkers in Mild Traumatic Brain Injury (mTBI) — NCT03221751.
- Registry record last updated 2024-02-26; status last verified 2024-02.
- Results first posted 2024-02-26.
- 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
The registry describes a Phase 4, randomized, triple-masked, parallel trial of prazosin hydrochloride versus placebo, sponsored by the VA Office of Research and Development. It records enrollment of 9, status as terminated, a start date of 2016-12-01, and primary completion on 2023-01-03.
The primary endpoint was change in CSF total-tau from baseline to the end of study over 10 weeks. The posted result is 11.0 pg/mL for 1 placebo participant; no prazosin endpoint value is reported. The registry notes that the one prazosin participant did not have a lumbar puncture at the study termination visit. No two-arm comparison is estimable from these results.
Three outcome measures are listed, with no secondary results and no analyses reported. The safety summary lists no serious adverse events or deaths and one other adverse event in each arm, with 1 participant at risk in each arm. The registry does not report the reason for termination, the statistical analysis plan, or how missing endpoint data were handled.