Improving Platelet Activity for Cerebral Hemorrhage Treatment - DDAVP Proof of Concept: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Improving Platelet Activity for Cerebral Hemorrhage Treatment - DDAVP Proof of Concept (NCT00961532), a na phase 2 study. The primary outcome is Change in Platelet Activity, Measured in Seconds on PFA-EPI Assay, From Pre to Post-treatment.

2. Clinical Question

This is a proof-of-concept question about a measured laboratory response, not a randomized comparison of DDAVP with another treatment or with no treatment. The study summary states that investigators intended to show improved platelet activity from baseline to 60 minutes after treatment start. The registry's endpoint title describes the outcome as a change in platelet activity, measured in seconds on the PFA-EPI assay, from pre- to post-treatment.

The assay's time to closure is interpreted in the opposite direction from the phrase platelet activity: a longer time indicates less platelet activity. The record notes that a time to closure of at least 172 seconds is consistent with an aspirin effect in the investigators' laboratory. That context explains the assay but does not establish the participants' baseline status or their response to DDAVP. Since no primary change estimate or uncertainty measure is reported, the registry record does not establish the direction, size, or precision of the observed change.

3. Trial Design

This completed Phase 2 study enrolled 14 participants with intracerebral hemorrhage. Northwestern University is listed as the sponsor. The record gives a start date of 2010-12 and a primary completion date of 2013-12. Its design is described as single-group, with no masking and allocation recorded as NA.

All participants in the listed group received DDAVP injection, described as desmopressin acetate. The regimen was 0.4 mcg/kg intravenously in 250 mL NS over 30 minutes. There is no separate control arm in the record. Therefore, the primary question is framed as a pre-treatment versus post-treatment measurement in the same study group, rather than as a contrast between randomized treatment groups.

The primary outcome was change in platelet activity measured in seconds on the PFA-EPI assay, with the post-treatment time point specified as 60 minutes after treatment start. The endpoint is described as a mean, with standard error as the dispersion measure. The registry record lists two outcome measures and one analysis, but does not provide a detailed statistical analysis plan or the primary outcome's numerical result.

The study also lists adverse events, including new fever at or above 100.4F; respiratory distress or pulmonary edema on chest radiography; rash; and hypotension, defined using systolic blood pressure below 100 mm Hg, new vasopressor use, or an increase in vasopressor dose by more than 25%. The record reports serious and other adverse-event figures for the DDAVP group. These safety observations belong to the experience of this single group and cannot provide a controlled comparison.

The registry does not report a separate control-group rationale, randomization procedure, masking procedure beyond the listed absence of masking, or a sample-size justification. The study's completed status does not, by itself, fill in any missing outcome result or analysis detail.

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 Change in Platelet Activity, Measured in Seconds on PFA-EPI Assay, From Pre to Post-treatment, measured over 60 minutes after treatment start.

The primary endpoint is change in platelet activity, measured in seconds using the PFA-EPI assay, from before treatment to 60 minutes after treatment started. The registry describes the assay as a point-of-care test that measures the time to closure of an aperture. EPI refers to epinephrine as the stimulant to platelet aggregation, rather than adenosine diphosphate.

The direction of this measurement matters for interpretation. A longer time to closure indicates less platelet activity; a shorter time is consistent with more activity. The registry record notes that, in the investigators' laboratory, a time to closure of at least 172 seconds is consistent with an aspirin effect. This is contextual information about assay interpretation, not a cutoff defining clinical benefit or an outcome result for this study.

Using a change from pre-treatment to post-treatment makes the question one of within-group change over time. It can describe whether the measured assay value shifted after the intervention, but without a control group it cannot by itself distinguish a treatment-associated shift from other explanations, such as natural change over time or measurement variability. The record does not report the mean change, its standard error, a confidence interval, or a test result for the primary endpoint. Accordingly, the direction and precision of the observed change are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a measurement in seconds, and the record specifies that it is summarized as a mean with standard error. A mean gives a measure of the central location of the observed values. A standard error describes the statistical uncertainty around an estimated mean; it is not the same thing as the spread of individual participant measurements. The actual mean change and standard error are not reported in the registry record, so their magnitudes cannot be interpreted.

What does a pre/post change estimate represent?

In a single-group pre/post design, the target contrast is the difference between measurements made at two times in the same group. Such an estimate can describe the average change observed across participants with measurements at both times. It does not automatically establish that the intervention caused the change. Time-related changes, measurement variability, and other influences may also contribute. A separate comparison group can help address some of these questions, but no such control group is listed for this study.

The endpoint's measurement direction should be kept distinct from the clinical phrase platelet activity. The assay records time to closure in seconds, and the record says that longer times indicate less platelet activity. Thus the interpretation of a change depends on whether the measured time increased or decreased. The registry provides no numerical pre/post result, so it does not reveal which direction the study's measured change took.

What would uncertainty measures add?

A confidence interval is a range of values compatible with the data and the analysis under its assumptions. It conveys precision as well as direction and size. A p-value, when reported, summarizes how unusual the data would be under a specified null hypothesis and model; it is not the probability that the null hypothesis is true, nor does it measure clinical importance. Neither a confidence interval nor a p-value for the primary outcome is reported in the registry record. No claim about statistical significance or precision can therefore be made from the listed endpoint description alone.

Standard error is an uncertainty summary for an estimate, while standard deviation describes variability among individual measurements. Confusing the two can make an outcome seem more or less variable than it is. The registry identifies standard error as the dispersion format but supplies no value and does not give the underlying distribution of individual measurements. It is consequently not possible to reconstruct the observed variation or check the statistical summary.

How should the planning illustrations be understood?

Planning illustrations based on an observed effect answer a hypothetical design question: how many participants per arm might be needed to detect a specified fraction of that effect under stated assumptions. The record describes illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions are not evidence that this single-group study used that design or that analysis. The registry does not report the study's own sample-size justification.

Such planning values are not observed power. They are prospective illustrations that depend on the chosen effect and statistical assumptions; they do not show the probability that the completed trial detected an effect. In this study, the primary numerical effect is not reported in the registry record, so the observed effect cannot be evaluated from the endpoint information. The planning assumptions also describe a two-arm design, whereas the registered study is single-group. They should not be mistaken for the original protocol or for a randomized comparison actually conducted.

Why does over-dispersion matter in general?

General statistical context: over-dispersion occurs when observed variability is greater than a model assumes. If a model understates variability, its standard errors may be too small and its intervals too narrow. This issue is especially relevant for outcomes whose variation does not follow a simple assumed distribution. The primary endpoint is described as a continuous assay measure and summarized by a mean and standard error. The registry record does not report a model assessment, distributional checks, or evidence of over-dispersion, so none should be presumed.

Likewise, the record does not describe adjustment for baseline values, covariates, repeated-measure structure, or other modeling choices. The endpoint title establishes a pre/post change question, but not the exact calculation or inferential procedure used. A single listed analysis does not disclose those details. They are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("DDAVP")
n   <- c(14)
m   <- c(68)
sp  <- c(24.1)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  DDAVP  14  68.000  90.174  15.935  120.065

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and one analysis, but does not explain how multiple outcomes were handled statistically. It does not report a multiplicity adjustment, a hierarchy of outcomes, or a plan for interpreting results across endpoints. Without that information, it is not possible to determine whether the reported analysis, if any, treated the primary endpoint as the sole confirmatory test or considered additional outcomes in a broader testing plan. The primary outcome result itself is not reported in the registry record.

Missing-data handling is also not described. The registry record does not report the number of participants with usable pre-treatment and post-treatment assay measurements, how missing measurements were handled, or whether any imputation or sensitivity analysis was conducted. Enrollment of 14 is not enough to establish how many participants contributed to the primary analysis. The analysis population and exclusions, if any, are not reported in the registry record.

Similarly, the record does not state whether the primary analysis followed a prespecified intention-to-treat, per-protocol, or other population definition. No detailed statistical analysis plan is reported. These omissions limit assessment of how outcomes were selected, how incomplete observations may have affected the estimate, and whether the reported analysis matched a prespecified approach. They do not establish that any particular procedure was or was not used; the relevant details are simply not reported in the registry record.

12. Safety Results

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

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: hypotension (7.1%), fever (7.1%).

The registry reports 2 serious adverse events among 14 at risk in the DDAVP group, and 0 other adverse events among 14 at risk. Hypotension and fever appear as the top serious adverse-event terms, each listed with 7.1%. These figures describe the events recorded for the study group and should not be read as a comparison with another treatment or with no treatment.

The record's event definitions include new fever at or above 100.4F; respiratory distress or pulmonary edema on chest radiography; rash; and hypotension defined by systolic blood pressure below 100 mm Hg, new vasopressor use, or an increase in vasopressor dose by more than 25%. These definitions clarify what the registry monitored, but they do not give details about timing, severity beyond the serious-event classification, attribution, or the clinical course of events. Those details are not reported in the registry record.

The serious-event terms and percentages should be understood as descriptive registry entries, not as proof of cause or as estimates of comparative risk. Because this was a single-group study, the listed event figures cannot determine whether DDAVP changed the likelihood of an adverse event relative to a control condition.

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

The record identifies a focused proof-of-concept question: whether mean platelet activity, measured by PFA-EPI, changed between pre-treatment and 60 minutes after DDAVP treatment began. It also specifies the assay's direction, the intervention regimen, and selected adverse-event information. These details make the intended measurement and study context clear.

They do not, however, establish the size or direction of the primary outcome. The numerical result for change in platelet activity is not reported in the registry record. No conclusion about an increase or decrease in assay time, the magnitude of change, or the precision of an estimate can be drawn from the endpoint description. The statement of investigator intent is a study objective, not a result.

Even if a pre/post change estimate were available, a single-group design would describe change over time rather than provide a controlled treatment effect. Without a separate comparison group, it would be difficult to separate an intervention-associated change from other influences on the measurement. The record does not support a randomized comparison or a direct claim about how DDAVP compares with another approach.

The safety entries likewise describe recorded events in the study group, rather than comparative risks. They offer limited context about observed serious and other adverse events, but do not establish causation or comparative safety. Additional details about event timing, attribution, and clinical course are not reported in the registry record.

In short, the available registry information supports interpretation of the study question and design, but not a conclusion about whether platelet activity changed or how dependable any change estimate would be. The study's completed status does not replace the missing primary outcome result.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its central question concerns a within-group laboratory change, while the study has no separate control arm. That distinction separates describing a change over time from estimating a contrast attributable to treatment. The design can address whether measurements shifted in the enrolled group, but it cannot by itself isolate the intervention's effect from time or other influences.

The endpoint also highlights the importance of measurement direction. PFA-EPI reports time to closure in seconds, and longer times indicate less platelet activity. A reader must therefore interpret the numerical direction rather than assume that a higher assay value means more activity. The registry provides this essential measurement context, but not the observed primary change.

Another statistical lesson is that a stated objective and an outcome definition are not substitutes for a reported estimate. The record identifies a mean change and standard error as the planned form of reporting, yet the primary outcome result is not reported in the registry record. Without that estimate and its uncertainty, the size, direction, and precision of the result cannot be evaluated.

Finally, planning calculations require careful separation from trial results. The record describes hypothetical sample-size illustrations using a two-arm design and specified assumptions, while the registered study is single-group. Those illustrations do not establish the trial's original design rationale, observed power, or a treatment effect. The distinction between design assumptions, observed data, and causal interpretation is central to reading this study statistically.

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 primary limitation for interpreting efficacy is that the numerical primary outcome is not reported in the registry record. The record names the measure, time point, summary type, and dispersion type, but gives no observed change estimate, standard error, confidence interval, or p-value. As a result, neither direction nor magnitude nor precision can be assessed.

The single-group design is an additional limitation. There is no separate control group, so the pre/post question does not provide a like-for-like contrast. Any measured shift would be difficult to attribute solely to DDAVP. The registry lists no random allocation and no masking, and it does not report further procedural detail about measurement conduct.

The enrolled group was 14 participants, but the primary analysis population and completeness of assay measurements are not reported in the registry record. Missing-data methods, analysis-population definitions, and sensitivity analyses are also not reported. This makes it impossible to assess whether incomplete measurements could affect the primary estimate.

The registry record does not report the sample-size justification or detailed statistical plan, including the approach to multiple outcomes. It lists two outcome measures and one analysis but does not explain how those outcomes informed inference. The adverse-event entries are descriptive and lack reported comparative data, attribution, and event-course detail. These limitations restrict conclusions to the design and recorded information rather than an assessment of efficacy or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Improving Platelet Activity for Cerebral Hemorrhage Treatment - DDAVP Proof of Concept — NCT00961532.
• Registry record last updated 2014-08-28; status last verified 2014-07.
• Results first posted 2014-08-28.
• 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

This completed Phase 2 study, sponsored by Northwestern University, enrolled 14 participants with intracerebral hemorrhage. The design was single-group, with no masking and allocation recorded as NA. Participants received DDAVP 0.4 mcg/kg intravenously in 250 mL NS over 30 minutes.

The primary outcome was change in mean platelet activity, measured in seconds on the PFA-EPI assay, from pre-treatment to 60 minutes after treatment started. Longer time to closure indicates less platelet activity. The primary numerical result is not reported in the registry record.

The record reports 2 serious adverse events among 14 at risk and 0 other adverse events among 14 at risk. Hypotension and fever are listed among the top serious terms, each with 7.1%. The single-group design and absence of a reported primary estimate limit interpretation of efficacy and comparative safety.