Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children: A Pilot and Feasibility Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children: A Pilot and Feasibility Study (NCT02840097), a randomized phase 2 study. The primary outcome is Pediatric Quality of Life Inventory (PedsQL).

2. Clinical Question

3. Trial Design

The registry describes TIC-TOC as a phase 2, randomized, triple-masked, parallel-group pilot and feasibility study. It lists tranexamic acid and placebo as the interventions and reports enrollment of 31 participants. The study summary describes a 40-patient pilot intended to assess the feasibility of two subsequent large-scale studies. The registry status is completed, with a start date of 2019-03-04 and a primary completion date of 2020-10-03.

There were three groups: tranexamic acid Dose A, tranexamic acid Dose B, and placebo. The listed group sizes for the primary outcome are 9, 10, and 12 participants, respectively. The two active regimens differed in both bolus and infusion dose. The placebo regimen used normal saline for both the bolus and infusion. Details of the randomization procedure, allocation ratio, masking procedures, and which roles were masked are not reported in the registry record.

The registry lists the PedsQL outcome at 6 months as primary. It also lists secondary outcomes covering functional status, memory, transfusion, intracranial hemorrhage progression, thrombosis, seizures, and biomarker testing. The record includes additional outcome measures beyond the primary measure, but comprehensive outcome estimates and comparative analyses for all of them are not reported in the registry record.

The study summary identifies feasibility as a central purpose. The posted outcome values therefore need to be read in the context of a small pilot, rather than as a definitive estimate of the effects of either regimen. The detailed feasibility criteria and results against those criteria 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 Pediatric Quality of Life Inventory (PedsQL), measured over 6 months.

The primary endpoint is the Pediatric Quality of Life Inventory (PedsQL), reported in quality-of-life units multiplied by months over 6 months. The registry describes PedsQL values as ranging from 0 to 100 quality-of-life units, with higher scores representing better outcomes. Assessments at 1 week, 1 month, 3 months, and 6 months contribute to an area-under-the-curve measure. This combines information across the stated follow-up times rather than relying on a single assessment.

As a general statistical concept, an area under the curve can represent both the level of a measure and how that level changes across the observation period. Its interpretation depends on the measurements used and the time scale; it is not interchangeable with a score recorded at just one visit. The registry identifies neurocognitive functioning and quality of life as the focus of the measure. The exact calculation procedure, handling of missing visits, and rules for combining measurements are not reported in the registry record.

The arm summaries report means and standard deviations. The posted values are 64.9 for Dose A, 60.2 for Dose B, and 67.2 for placebo. These summaries describe the observed groups; by themselves they do not establish that group differences are attributable to treatment. The comparative estimate posted for Dose B versus placebo is a mean difference, with an interval reflecting uncertainty around that estimate.

7. Results Posted in the Registry

• Tranexamic Acid Dose B: mean 60.20 versus 67.20 on control; difference -7.00 (95% CI -20.64 to 6.64), standardized effect d = -0.41; z-test p = 0.315.

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.

Number of Participants With Seizures

• 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:
  • Tranexamic Acid Dose B: 0.0% (0/10) versus 8.3% (1/12) on control; risk difference -8.3 percentage points (95% CI -24.0 to 7.3); unadjusted two-proportion z-test p = 0.350.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tranexamic Acid Dose B and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning functional status, memory, blood transfusion, intracranial hemorrhage progression, thrombosis, seizures, and biomarker testing. These outcomes address different aspects of the study’s clinical and feasibility context and do not measure the same construct as the primary PedsQL area-under-the-curve outcome. Their pattern therefore cannot be treated as a single confirming or contradicting result for the primary comparison.

The posted secondary results are incomplete as a set of comparative estimates. The seizure outcome includes arm counts and an unadjusted risk-difference estimate for Dose B versus placebo. Comparative results for the other listed secondary outcomes are not reported in the registry record. This limits any broad assessment of consistency across secondary outcomes. The absence of a posted estimate is not evidence that groups were the same on that outcome.

General: Secondary outcomes can help describe the range of observations in a trial, but they are often numerous and may be exploratory. When many outcomes are examined, some apparent differences can arise by chance. A multiplicity procedure can address the increased chance of false-positive findings, but no such adjustment is reported for the posted secondary result. The original plan for interpreting secondary endpoints is not reported in the registry record.

Secondary findings should therefore be considered alongside, not as substitutes for, the primary result. In this pilot, the primary estimate itself is imprecise, and the registry does not provide a complete set of secondary comparative analyses. Neither isolated secondary observations nor non-reported outcomes resolve the uncertainty in the primary comparison. The listed outcome domains can inform what the investigators intended to monitor, while the available numerical results support only a limited description of what was posted.

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

• Glasgow Outcome Scale-Extended (GOS-E) Peds
• Digit Span Recall Test
• Blood Transfusion
• Intracranial Hemorrhage Progression
• Number of Participants With Any Non-cerebral Venous or Arterial Thrombosis
• Number of Participants With Seizures
• Biomarker Testing

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean difference describe?

General: A mean difference compares the average outcome in one group with the average in another, using the stated order of groups to set its direction. For this posted comparison, the estimate is for Dose B versus placebo. The estimate of -7.0 is the reported mean difference. The negative sign indicates that the Dose B mean was lower than the placebo mean on the scale used for this outcome. The estimate is not a percentage or a ratio; it is expressed in the outcome’s units.

The record reports group means and standard deviations for all three arms. A standard deviation describes variability among observations within a group; it is not the uncertainty interval for the group mean. The reported comparison also includes a pooled standard deviation of 16.97 and a standardized effect estimate of -0.412. These are summary statistics for the posted comparison, not evidence that the observed difference is a stable or clinically important effect.

How should the confidence interval be read?

General: A confidence interval gives a range of values compatible with the data and the method used to calculate the interval. It reflects uncertainty in the estimated group difference. The interval for the primary comparison extends from -20.64 to 6.644. It includes zero and values in either direction, which indicates that the data do not pin down the direction or size of the difference precisely. A confidence interval is not a range containing every participant’s outcome, and it does not assign a probability to the true value being inside this particular interval.

What does the p-value add?

General: A p-value describes how unusual data at least as incompatible with a specified null model would be, under the assumptions of the analysis. It does not measure the probability that the null hypothesis is true, nor does it measure clinical importance. The unadjusted p-value for the primary comparison is 0.315. It should be considered alongside the estimated difference and its confidence interval, not used alone to characterize the result. The record does not report a multiplicity adjustment for this p-value.

Why does the pilot context matter?

The primary-outcome groups contain 9, 10, and 12 participants. With small groups, estimates can be sensitive to the outcomes of a limited number of participants, and uncertainty can remain substantial. Random allocation is recorded, but further details of its implementation and of the analysis population are not reported in the registry record. The study summary describes the trial as a pilot to evaluate feasibility for later studies, so the posted comparison is best treated as an exploratory estimate rather than a precise population-level effect.

General: Statistical significance and precision are different ideas. A p-value summarizes compatibility with a null model under specified assumptions; the confidence interval describes the range of effect sizes compatible with the data and method. Neither alone answers whether a difference would be clinically important. The registry does not report a clinical-importance threshold for this outcome.

What can be inferred from the listed analyses?

The posted primary comparison is an unadjusted comparison of Dose B with placebo. A primary comparative estimate for Dose A is not reported in the registry record. For the secondary seizure outcome, the record lists a risk difference and an unadjusted p-value, but does not list reported analyses for that outcome. The exact methods used for the primary estimate, including assumptions beyond the listed summary statistics, are not reported in the registry record.

General: Over-dispersion occurs when count or binary outcomes vary more than a chosen statistical model expects. When present, it can make standard errors too small and confidence intervals too narrow if the model does not account for it. The registry does not report an over-dispersion assessment or a model for the primary continuous outcome. This is a general consideration, not a claim that over-dispersion affected this trial’s analysis.

The registry record does not report the original sample-size justification, planned primary analysis details, interim analyses, missing-data method, or analysis-population definitions. Those omissions limit how fully the posted estimates can be assessed against the trial’s original statistical plan. They should not be filled in by assumption.

11. Confidence Intervals and Precision

The primary estimate for Dose B versus placebo is a mean difference of -7.0. Its confidence interval extends from -20.64 to 6.644. This interval is broad and crosses zero, so the observed data are compatible with a negative difference, no difference, or a positive difference under the reported interval method. The interval communicates substantial uncertainty about both the direction and size of the group difference.

General: Precision concerns how narrowly an estimate is determined by the data and method. A narrow confidence interval indicates less uncertainty about the range of compatible values; a wide interval indicates more uncertainty. The interval does not show the distribution of individual outcomes, and it should not be interpreted as a prediction interval for an individual participant.

The arm sizes for the primary outcome were 10 in Dose B and 12 in placebo. The registry also reports standard deviations of 12.3 and 20.0 for those groups, respectively. These group summaries give context for the estimated comparison, but the confidence interval is the direct description of uncertainty in the mean difference. The registry does not report a clinical threshold that would distinguish a small from an important PedsQL difference.

The point estimate alone would give an incomplete account: it does not show how much uncertainty surrounds the estimate. The interval also does not establish that all values within it are equally plausible, and it depends on the statistical method and assumptions used. Details of that method are not reported in the registry record. Because this is a small pilot, the estimate is useful as a description of the posted data but should not be treated as a precise estimate for a broad population.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect in the Dose B versus placebo comparison. They are not the original trial’s design calculations; the trial’s own design assumptions are not reported in the registry record. The illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers detecting the stated fraction of the observed effect.

For a continuous outcome such as the PedsQL measure, the figures refer to participants per arm, not a total across both arms. The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true effect and the assumptions held. The 90% power column gives the corresponding per-arm planning figure for a design with a 90% chance under those assumptions. This is not observed power.

The planning rows consider 100%, 75%, and 50% of the observed effect. Smaller effects require more participants to detect under otherwise unchanged assumptions. The figures rise as the effect being targeted becomes smaller. They are scenario-based illustrations, not forecasts of what a future study will find and not guarantees that a study of that size will produce a particular result.

The observed estimate comes from a small pilot and is uncertain, as reflected by its confidence interval. Consequently, planning directly from that estimate can be sensitive to how representative it is of a future study. The illustration does not account for design features or analysis choices not listed in its assumptions, such as attrition or a different outcome model. Those details of the original trial’s sample-size rationale are not reported in the registry record. For any outcome outside the continuous-outcome setting, interpretation of planning units would depend on the specific stated calculation; the primary comparison’s figures are participants per arm.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -7.000; pooled standard deviation σ = 16.973.
2. n = 2 × (1.96 + 0.842)² × 16.973² / -7.000² = 92.3, rounded up to 93 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -7                      # observed difference in means
sigma <- 16.972934336761                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2840097)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 93 (80% power), 124 (90% power)
 75% of observed effect: n per arm = 165 (80% power), 220 (90% power)
 50% of observed effect: n per arm = 370 (80% power), 495 (90% power)
power.t.test: 93.3 
Simulated power at n = 93 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and multiple secondary outcome measures. It does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment for multiple comparisons. The primary comparison has an unadjusted p-value, and the posted secondary seizure comparison is also unadjusted. When several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. General: Multiplicity procedures are ways to control or manage that increased chance, but their choice depends on the study’s objectives and analysis plan. The intended procedure for this trial is not reported in the registry record.

The record does not describe how missing PedsQL assessments were handled, whether all randomized participants were included in the primary analysis, or how participants with incomplete follow-up were treated. It also does not report the definitions of the analysis populations, such as an intention-to-treat population. These omissions matter because the primary outcome uses assessments across several follow-up times, and missing measurements could affect an area-under-the-curve calculation. The extent and pattern of missing data are not reported in the registry record.

The registry also does not report the original primary analysis plan in enough detail to determine the planned model, covariates, assumptions, or any interim analyses. Randomization and triple masking are listed as design features, but the record does not give procedural details or identify which participants, investigators, or assessors were masked. These details should not be inferred from the design labels.

These reporting gaps do not establish that the study used an inappropriate method or that data were missing. They mean that readers cannot assess those aspects of the analysis from the registry record. The posted estimate and its uncertainty can still be described, but a fuller appraisal of bias control, missing-data sensitivity, and the alignment between planned and reported analyses is not possible from the available record.

15. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: seizure (8.3%).

The registry reports serious adverse events in the three groups as counts of participants at risk and participants affected. No serious adverse events were recorded in Dose A or Dose B; one participant in the placebo group was affected. The listed serious event term is seizure, reported as 8.3%. No deaths were reported in any of the three groups.

The record also reports other, non-serious adverse events: 9 participants in Dose A, 10 in Dose B, and 10 in placebo were affected. These are counts of participants, not counts of distinct events. The record does not provide a detailed breakdown of the other events in this summary, and the small group sizes mean that the counts should be read descriptively rather than as stable comparative rates.

General: Adverse-event counts describe events recorded during the study; they do not by themselves establish whether an event was caused by an intervention. A comparison of safety between groups requires attention to event definitions, observation time, and uncertainty, as well as the number of participants exposed. Detailed causal assessments and statistical comparisons of serious adverse events are not reported in the registry record. These figures are a limited account of the events recorded in this pilot, not a comprehensive estimate of safety.

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

The results document observed PedsQL summaries in three small groups and a reported comparison of Dose B with placebo. The mean difference was -7.0, with a confidence interval from -20.64 to 6.644. This interval includes differences in either direction and does not give a precise estimate of the group contrast. The registry also reports a Dose A mean, but no primary comparative estimate for Dose A versus placebo.

The data do not establish a definitive answer about the effect of tranexamic acid on the primary outcome. They also do not establish that the groups are equivalent: an interval that includes zero can still include differences that may be meaningful, and the registry does not state a clinical-importance threshold. The unadjusted p-value should not be translated into a probability that a regimen works or does not work.

The record describes this as a pilot and feasibility study intended to inform later large-scale studies. Its small outcome groups and imprecise estimate fit an exploratory role, but the actual feasibility criteria and findings are not reported in the registry record. The findings should not be generalized automatically to all injured children, other doses, other settings, or outcomes that were not reported.

The listed secondary outcomes and adverse-event counts add context about what the study monitored, but the registry does not report complete comparative analyses across those outcomes. The serious-event counts are also too limited to provide a broad assessment of uncommon harms. Overall, the record supports a cautious description of the observed groups and uncertainty, not a clinical recommendation or a conclusive judgment about benefit or harm.

17. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a pilot study can produce an initial estimate while leaving substantial uncertainty about the size and direction of a group difference. Randomization is recorded, and the primary comparison has both a point estimate and a confidence interval. Seeing those together is more informative than relying on a p-value alone: the estimate describes the observed contrast, while the interval shows that a broad range of differences remains compatible with the data.

The trial’s stated feasibility purpose also matters for statistical interpretation. A pilot can help assess whether later studies are feasible and can provide preliminary outcome information. However, the registry record does not report the feasibility criteria or their results, and the primary outcome estimate is based on small groups. Planning illustrations based on that estimate should therefore be treated as scenarios rather than as assured requirements for a future study.

The record further shows why interpretation depends on reporting completeness. It lists several secondary outcomes, but numerical comparisons are not reported for all of them. It also does not report the original statistical plan, missing-data approach, analysis populations, or multiplicity strategy. Those details affect how confidently readers can connect the posted results to the trial’s intended analyses.

For clinical researchers, the useful statistical lesson is not a conclusion about treatment. It is the need to distinguish observed summaries from comparative inference, to read confidence intervals as measures of uncertainty, and to consider the study’s pilot purpose and reporting limitations when interpreting an estimate.

18. 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 outcome groups are small: the primary endpoint summaries include 9 participants in Dose A, 10 in Dose B, and 12 in placebo. This limits the precision of group estimates and makes the primary comparison uncertain. The reported confidence interval spans negative and positive differences, so the direction and magnitude of the population contrast remain unclear.

The registry reports a primary comparative estimate only for Dose B versus placebo. Although a mean is posted for Dose A, a comparative estimate for Dose A versus placebo is not reported in the registry record. This prevents a direct assessment of the two active regimens against the comparator using a posted primary analysis.

The study summary describes a 40-patient pilot, while the registry lists enrollment of 31. The record does not explain the difference between those figures, so no reason for it should be inferred. The registry also does not report eligibility details, baseline characteristics, reasons for nonparticipation, or participant flow through follow-up.

Important analysis details are not reported in the registry record, including missing-data handling, analysis-population definitions, the original statistical analysis plan, and any multiplicity strategy. The PedsQL measure uses assessments across multiple times, but the handling of incomplete visits is not specified. Comparative results for most listed secondary outcomes are also not reported.

Finally, safety counts from a small pilot provide limited information about uncommon events, and the registry does not give detailed event-level descriptions or causal assessments in the posted summary. These limitations constrain interpretation of both outcome differences and adverse events; they do not, by themselves, indicate that a particular result is biased.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children: A Pilot and Feasibility Study — NCT02840097.
• Registry record last updated 2021-09-05; status last verified 2021-09.
• Results first posted 2021-09-05.
• 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.

22. Record Summary

NCT02840097 is a completed phase 2 randomized, triple-masked, parallel-group pilot and feasibility study of tranexamic acid versus placebo in injured children. The registry lists enrollment of 31 and describes a 40-patient feasibility pilot intended to inform later large-scale studies. The study began on 2019-03-04 and reached primary completion on 2020-10-03.

The primary outcome was PedsQL over 6 months, with measurements at 1 week, 1 month, 3 months, and 6 months combined into an area-under-the-curve measure. The posted comparison of Dose B with placebo reported a mean difference of -7.0, a confidence interval from -20.64 to 6.644, and an unadjusted p-value of 0.315. The interval reflects substantial uncertainty. Further details of the original statistical plan and several secondary analyses are not reported in the registry record.