Cold-stored Platelet Early Intervention in TBI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cold-stored Platelet Early Intervention in TBI (NCT04726410), a randomized phase 2 study. The primary outcome is Study Feasibility.

2. Clinical Question

3. Trial Design

This was a phase 2 randomized, parallel-group trial with enrollment recorded as 100. The registry lists 50 participants in the cold-stored platelet arm and 50 in the standard care arm. The trial status is completed. The record gives a start date of 2022-03-21 and a primary completion date of 2024-05-13. The brief summary describes a proposed 3 year, open-label, single-center randomized pilot, while the design fields identify single masking. The record does not explain which participants, if any, were masked, or reconcile the masking description with the open-label wording.

The intervention arm is described as early infusion of up to 2 units of urgent-release cold-stored platelets. The comparator arm is described as standard care therapy. The trial summary identifies patients with traumatic brain injury requiring platelet transfusion as the intended population. Its stated purpose included assessing feasibility, efficacy, and safety, with feasibility as the primary outcome and 6-month Extended Glasgow Outcome Scale as a principal secondary clinical outcome. The posted outcome record includes secondary measures of mortality, TBI progression, orientation and amnesia, and transfusion-related or thromboembolic events.

The registry record does not report the allocation-concealment procedure, the randomization sequence method, the masking procedures, or detailed criteria for inclusion and exclusion in the outcome descriptions. It also does not report the protocol-specific definition of standard care. The record gives an enrollment figure but no sample-size justification. No trial analysis is listed in the reported-analyses entries. The design can therefore be described from its randomized, parallel structure and arm assignments, but details needed to assess implementation and prespecification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

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 Study Feasibility, measured over 6 months.

The primary endpoint is titled Study Feasibility and is recorded in participants over a 6-month timeframe. Its description defines feasibility through several steps: the proportion of eligible patients who can be randomized, enrolled, adhere to protocol, and complete follow-up. This makes feasibility a question about whether the trial procedures can be carried out in the intended clinical setting, rather than a direct measure of neurological recovery or survival.

Feasibility is useful in a pilot trial because successful recruitment, delivery of assigned care, protocol adherence, and outcome follow-up are prerequisites for a larger clinical evaluation. If these processes cannot be completed reliably, estimates of clinical outcomes may be difficult to interpret or apply to a future study. The record identifies the endpoint’s components, but does not report component-specific counts or proportions, a threshold for judging feasibility, or separate results for randomization, enrollment, adherence, and follow-up completion. It is therefore not possible to determine from the posted primary entries which feasibility steps were achieved or where difficulties may have occurred.

The arm entries record 50 participants for cold-stored platelets and 50 for standard care. The comparison summary also encodes an arm-level proportion of 1.0 in each group and a risk difference of 0.0. Because the primary outcome is described as a combination of process measures, these entries should not be interpreted as evidence that every component of feasibility was completed. The registry record does not explain how the recorded count and comparison relate to the component-based endpoint description. The clinical outcome measures, including 6-month Extended Glasgow Outcome Scale, are secondary rather than the primary feasibility endpoint.

7. Results Posted in the Registry

• Cold-stored Platelet (CSP): 100.0% (50/50) versus 100.0% (50/50) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

24-hour Mortality

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Cold-stored Platelet (CSP): 2.0% (1/50) versus 0.0% (0/49) on control; risk difference 2.0 percentage points (95% CI -1.9 to 5.9); unadjusted two-proportion z-test p = 0.320.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cold-stored Platelet (CSP) and the control. The interval gives the range of effects that remain compatible with the data.

In-hospital Mortality

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Cold-stored Platelet (CSP): 12.0% (6/50) versus 14.3% (7/49) on control; risk difference -2.3 percentage points (95% CI -15.6 to 11.0), risk ratio 0.84 (0.30–2.32); unadjusted two-proportion z-test p = 0.736.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cold-stored Platelet (CSP) and the control. The interval gives the range of effects that remain compatible with the data.

TBI Progression

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Cold-stored Platelet (CSP): 16.7% (8/48) versus 23.4% (11/47) on control; risk difference -6.7 percentage points (95% CI -22.8 to 9.3), risk ratio 0.71 (0.31–1.61); unadjusted two-proportion z-test p = 0.412.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cold-stored Platelet (CSP) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover different domains: mortality, TBI progression, neurological or cognitive assessment, and adverse events associated with transfusion or thrombosis. Their relationship to the primary feasibility result is indirect. Feasibility asks whether the trial processes can be completed; secondary clinical outcomes describe health events or assessments after assignment. A feasibility result cannot substitute for missing clinical outcomes, and a clinical outcome comparison does not by itself establish that recruitment, adherence, and follow-up procedures were workable.

The posted numeric comparisons for mortality and TBI progression do not show a clear separation between groups, and their confidence intervals include no difference. The registry does not provide numeric results for several other listed secondary outcomes, including the principal secondary clinical outcome of 6-month Extended Glasgow Outcome Scale. The record therefore gives an incomplete view of the planned secondary outcome set. It is not appropriate to infer a consistent pattern across outcomes that lack posted estimates.

Secondary findings generally carry less confirmatory weight when many outcomes are examined without a reported testing strategy. The registry record does not state whether the secondary outcomes were arranged in a prespecified hierarchy, whether multiplicity was controlled, or which outcomes were intended as exploratory. Unadjusted p-values do not account for the number of comparisons being considered. Even a small p-value in a broad set of secondary analyses would need cautious interpretation unless the analysis plan specified how such results would be evaluated.

The primary outcome remains the trial’s feasibility measure, but its component results are not reported separately. The posted entry therefore does not fully resolve the operational question, while the secondary outcomes are either uncertain or not numerically reported. Taken together, the record supports cautious description of the available estimates rather than a broad conclusion about clinical outcomes or a claim that one treatment approach is superior.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• 6-month Extended Glasgow Outcome Scale (GOS-E)
• 24-hour Mortality
• In-hospital Mortality
• TBI Progression
• Galveston Orientation and Amnesia Test (GOAT)
• Incidence of Allergic/Transfusion Reaction
• Incidence of Transfusion Related Acute Lung Injury (TRALI)
• Incidence of Thromboembolic Events

9. Statistical Interpretation

10. Statistical Methods Explained

Random assignment is intended to make treatment groups comparable, on average, with respect to factors that could affect outcomes. This trial is listed as randomized and parallel: participants were assigned to cold-stored platelets or standard care and followed in the assigned groups. Randomization can reduce systematic differences at the start of a trial, but it does not guarantee that every measured or unmeasured characteristic will be balanced, especially in a pilot study. The registry record does not report the sequence-generation or allocation-concealment methods, so those aspects of the randomization process cannot be assessed from the posted record.

What does a risk difference describe?

For a binary outcome, a risk difference is the difference between the observed event proportions in the intervention and comparator groups. A value of zero represents no observed difference in those proportions. A positive or negative value indicates the direction of the contrast according to the ordering used for the comparison. The risk difference is an absolute measure, expressed on the probability scale, and can be easier to relate to event counts than a relative measure. It remains an estimate from the observed trial data, not a guarantee of the effect that would occur in another population.

The posted secondary comparisons use risk differences. For 24-hour mortality, the estimate is 0.02 with a confidence interval from -0.019 to 0.059. For in-hospital mortality, the estimate is -0.023 with a confidence interval from -0.156 to 0.110. For TBI progression, the estimate is -0.067 with a confidence interval from -0.228 to 0.093. Each interval includes zero. These intervals therefore do not rule out no difference, while also allowing differences in either direction. They should be interpreted alongside the event counts and the limitations of the registry reporting.

What does a confidence interval add?

A confidence interval conveys the uncertainty around an estimated effect. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision. The interval is not a range in which the true effect is guaranteed to lie, and it is not a probability statement about the particular trial effect. Its width depends in part on the amount of information in the data, including the number of observed events. When event counts are limited, binary-outcome estimates can remain uncertain even when the point estimate appears near zero.

Here, the intervals for the posted secondary risk differences cross zero and extend to values in both directions. This matters because a point estimate alone can give an overly definite impression. The results do not establish equivalence, which would require a prespecified equivalence margin and an analysis designed to assess it. The registry record does not report such a margin or an equivalence analysis.

How should the p-values be read?

The unadjusted p-value is a measure of how incompatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The posted unadjusted p-values are 0.32 for 24-hour mortality, 0.736 for in-hospital mortality, and 0.412 for TBI progression. Read with the estimates and confidence intervals, they do not provide strong evidence against a null difference. They also do not prove that there is no effect. The registry record does not list adjusted analyses for these outcomes.

Because these are secondary outcomes, the p-values also need to be considered in the context of multiple comparisons. Testing multiple outcomes creates more opportunities for a result to appear noteworthy by chance. The record does not report a multiplicity adjustment or a hierarchy of confirmatory secondary hypotheses. The secondary p-values should therefore be treated as exploratory rather than as isolated confirmatory tests.

What is the role of planning illustrations?

Sample-size illustrations based on an observed effect can show how a future study’s required enrollment changes when the target effect is made smaller or larger. They are planning scenarios, not evidence about the probability that the completed trial detected an effect. The registry’s assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as stated fractions of the observed effect. For in-hospital mortality, the illustration lists 3,429 participants per arm for 80% power when planning for 100% of the observed effect, and 6,209 participants per arm when planning for 75% of the observed effect. These are illustrative planning quantities, not observed trial results or observed power.

Using an effect estimated from a small pilot can make planning sensitive to random variation in that estimate. A future design may need external clinical and design considerations beyond the observed effect. The registry record does not report the trial’s own sample-size justification, so these illustrations should not be attributed to the original design. The record also does not report interim analyses, a detailed statistical analysis plan, or the methods used for handling missing data. Those omissions limit assessment of whether each analysis followed prespecified procedures.

11. Confidence Intervals and Precision

The main feature of the posted secondary comparisons is uncertainty around the risk-difference estimates. The confidence interval for 24-hour mortality runs from -0.019 to 0.059 around an estimate of 0.02. For in-hospital mortality, the interval runs from -0.156 to 0.110 around an estimate of -0.023. For TBI progression, it runs from -0.228 to 0.093 around an estimate of -0.067. Each interval crosses zero, so the posted data are compatible with no difference as well as with differences in either direction.

The intervals are important because the point estimates alone can appear more conclusive than the evidence supports. In general, a confidence interval describes the range of effect estimates that are reasonably compatible with the data under the statistical method used. It does not guarantee that the true effect falls inside the interval. The interval’s width gives an indication of precision: wider intervals leave greater uncertainty about both the direction and magnitude of an effect.

These outcomes have limited event counts in the posted summaries, and estimates from binary outcomes can be imprecise when events are sparse. The registry record does not report confidence intervals for every listed secondary outcome, and it does not post a numerical result for the principal secondary clinical outcome, 6-month Extended Glasgow Outcome Scale. Consequently, precision cannot be assessed for those outcomes from the record. The primary comparison is recorded with a risk difference of 0.0 and limits of 0.0 and 0.0, but the record does not explain how that representation relates to the component-based feasibility description. It should not be taken as a general guarantee of precision for the separate feasibility processes.

The posted results do not establish that the groups are equivalent. A non-significant comparison and an interval that crosses zero are not, on their own, evidence of equivalence. Demonstrating equivalence requires a prespecified margin defining differences small enough to be considered practically similar. Such a margin and an equivalence analysis are not reported in the registry record.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes, including 6-month Extended Glasgow Outcome Scale, mortality at different timepoints, TBI progression, GOAT, allergic or transfusion reactions, TRALI, and thromboembolic events. Testing or estimating multiple outcomes raises a multiplicity issue: when many comparisons are considered, some results may appear unusual by chance even if there is no underlying effect. A prespecified hierarchy or adjustment method can help clarify which comparisons are confirmatory and how the rest should be interpreted.

No multiplicity adjustment, outcome hierarchy, or statistical plan for secondary testing is reported in the registry record. The posted p-values are described as unadjusted. They should not be interpreted as if each were the sole planned test. The record also does not report interim analyses or stopping rules, so their existence or absence cannot be inferred.

Missing-data methods and analysis populations are not reported in the registry record. The record does not state whether the analyses followed intention-to-treat principles, whether participants were analyzed according to assigned group, how missing outcome assessments were handled, or whether any per-protocol analysis was conducted. These details matter because exclusions or incomplete follow-up can affect the comparability created by randomization. The primary endpoint itself includes follow-up completion as a feasibility component, but no component-specific missingness results are posted.

Some secondary outcome denominators differ between groups or across outcomes. The record does not explain the reasons for those differences or describe how they were handled analytically. That limits interpretation of the risk estimates and makes it difficult to distinguish outcome-specific eligibility, missing observations, and other denominator changes. No conclusions about the analysis population or missing-data mechanism should be inferred from the reported counts alone.

Finally, the record lists no reported analyses. This does not establish that no analyses were conducted; it means that analysis details are not reported in the registry record. Without a statistical analysis plan, outcome hierarchy, missing-data procedures, and analysis-population definitions, readers cannot assess whether the posted comparisons match prespecified methods.

13. 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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: other (8.2%), pneumonia (6.0%), acute kidney injury (4.0%), seizures (2.0%), pulmonary consolidation (2.0%).

The adverse-event record reports serious adverse events affecting 9 participants in the cold-stored platelet group and 8 in standard care. The reported numbers at risk for this summary are 50 and 49, respectively. Other adverse events are recorded as affecting 0 participants in each group, with the corresponding at-risk counts of 50 and 49. Death counts in the adverse-event record are 6 and 7, respectively. These are descriptive safety entries, not adjusted comparisons or evidence about the cause of an event.

The listed serious-event terms include other at 8.2%, pneumonia at 6.0%, acute kidney injury at 4.0%, seizures at 2.0%, pulmonary consolidation at 2.0%, and deep vein thrombosis at 2.0%. These term percentages should not be treated as mutually exclusive categories or added together; the registry record does not explain their overlap or give the full event-level coding details. The summaries also do not establish whether every event was judged related to the intervention.

Safety counts need to be interpreted in light of the study’s size, the different denominators, and the absence of reported adjusted analyses. Descriptive counts can identify events recorded during the trial, but they do not by themselves establish comparative risk or causation. The registry record does not report the adjudication procedures, severity criteria, or attribution methods for these events.

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

The posted results describe a completed randomized pilot trial comparing early infusion of urgent-release cold-stored platelets with standard care in patients with traumatic brain injury requiring platelet transfusion. They provide arm counts, a primary feasibility summary, and numeric comparisons for selected secondary outcomes. For the posted mortality and TBI progression comparisons, the estimates are uncertain and the confidence intervals include zero. These findings do not establish a clear difference between assigned groups.

The primary endpoint is intended to assess whether eligible patients could be randomized, enrolled, adhere to protocol, and complete follow-up. The primary arm entries record 50 participants in each group, but the record does not report each component of that endpoint separately. The primary summary therefore cannot establish how well each feasibility process was achieved. The registry record also does not provide numeric results for the principal secondary clinical outcome, 6-month Extended Glasgow Outcome Scale.

These results should not be interpreted as proof that the interventions are equivalent or that there is no clinically important difference. The confidence intervals allow effects in either direction, and a pilot’s limited event information may not estimate clinical effects precisely. Nor should the posted estimates be treated as definitive evidence of benefit or harm. The record does not provide a reported multiplicity strategy, missing-data methods, or analysis-population definitions, all of which affect how secondary findings should be weighed.

The registry entries also do not explain how the primary arm-level values correspond to the endpoint’s component-based definition. That is a reporting limitation, not a basis for assuming success or failure of the feasibility criteria. Similarly, the adverse-event counts describe recorded events but do not establish causation or comparative safety. A careful reading is therefore narrow: the record reports the trial design and selected outcome summaries, while leaving important questions about feasibility components, clinical outcomes, and analysis methods unresolved.

15. Why This Trial Matters Statistically

This trial is statistically important because it places operational feasibility at the center of a randomized pilot study. In a trial that depends on urgent intervention for patients with traumatic brain injury, the ability to identify eligible patients, randomize and enroll them, deliver assigned care, and obtain follow-up is central to the design’s practicality. A feasibility endpoint can help determine whether those processes are measurable and reportable before a larger clinical comparison is undertaken.

The registry record also illustrates why endpoint definitions and outcome reporting need to align. The primary endpoint is described through several distinct process components, while the posted primary entries are counts by arm and a comparison encoded as equal arm-level values. Without separate component results or an explanation of the encoding, readers cannot tell which aspects of feasibility the primary summary captures. Clear reporting would allow clinical and statistical readers to distinguish recruitment performance, adherence, and follow-up rather than treating them as interchangeable.

The trial’s clinical secondary outcomes remain relevant, but their estimates require cautious interpretation. Confidence intervals that include zero do not establish equivalence, and unadjusted secondary analyses are harder to treat as confirmatory when many outcomes are listed. The registry’s absence of reported results for some listed outcomes further limits a comprehensive assessment.

The record also emphasizes the value of transparent statistical reporting. Definitions of analysis populations, missing-data methods, multiplicity procedures, and the relation between outcome descriptions and posted statistics help readers understand what the results can support. For this trial, these details are not reported in the registry record. The available information can still describe the randomized comparison and the posted estimates, but it does not support a complete evaluation of the trial’s feasibility processes or clinical outcome profile.

16. 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.

Several limitations arise from the registry record for this trial. The most direct concerns the primary endpoint: it is defined as the proportion of eligible patients who can be randomized, enrolled, adhere to protocol, and complete follow-up, but the posted primary entries do not give separate results for these components. The count of participants in each arm does not reveal how many eligible patients were approached, how many could not be enrolled, or whether participants completed each required process. No feasibility threshold is reported.

The design description also contains wording that is not reconciled in the record: the brief summary calls the trial open-label, while the design fields list single masking. The record does not explain who was masked or how masking was implemented. Allocation-concealment procedures, the randomization method, detailed eligibility criteria, and the content of standard care are not reported in the outcome record.

Clinical outcome reporting is incomplete. Although 6-month Extended Glasgow Outcome Scale is identified as a principal secondary clinical outcome, no numeric result for it is posted in the outcomes summarized. The registry lists other secondary measures, but numeric comparisons are available for only a subset. The record does not report why denominators vary across some outcomes or how missing observations were handled.

The statistical analysis plan, analysis populations, multiplicity procedures, and any interim analyses are not reported in the registry record. Consequently, readers cannot determine whether the posted analyses follow prespecified methods or how secondary findings were intended to be interpreted. The confidence intervals for the available clinical comparisons are broad enough to permit differences in either direction, and no equivalence margin is reported. The safety entries are descriptive and do not include reported attribution or adjudication methods. Together, these limitations mean that the posted record offers an incomplete account of both feasibility performance and clinical outcomes.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Cold-stored Platelet Early Intervention in TBI — NCT04726410.
• Registry record last updated 2025-05-11; status last verified 2025-04.
• Results first posted 2025-04-29.
• 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.

20. Record Summary

The registry describes a completed phase 2 randomized parallel-group trial of early cold-stored platelets versus standard care for traumatic brain injury. Enrollment is recorded as 100, with 50 participants in each arm. The primary endpoint is Study Feasibility over 6 months, described in terms of randomization, enrollment, protocol adherence, and follow-up completion. The posted primary entries do not report those components separately.

Numeric secondary comparisons are posted for 24-hour mortality, in-hospital mortality, and TBI progression. Their risk-difference confidence intervals include zero. The registry lists additional secondary outcomes, including 6-month Extended Glasgow Outcome Scale, without posting numerical results for all listed measures. Serious adverse event counts are descriptive and do not establish causation.

The record does not report a statistical analysis plan, multiplicity procedure, missing-data methods, or analysis-population definitions. The available results therefore support cautious description of the posted estimates, but not a definitive conclusion about clinical effects or a complete assessment of trial feasibility.