Reducing Hemarthrosis in Tibial Tubercle Osteotomy by the Administration of Intravenous Tranexamic Acid: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reducing Hemarthrosis in Tibial Tubercle Osteotomy by the Administration of Intravenous Tranexamic Acid (NCT03606109), a randomized phase 4 study. The primary outcome is Perioperative Blood Loss.

2. Clinical Question

This distinction matters for interpretation. Randomization is recorded, but the available arm labels do not identify randomized treatment assignments. Without an unambiguous account of which participants received TXA and what the comparator received, the posted group difference should be described as a difference between the named HTO and TTO groups, not as a treatment effect attributable to TXA. The registry record also does not report a separate measure of hemarthrosis in the posted primary outcome details. Blood loss may be relevant to the study’s stated purpose, but the record does not establish that the measure directly quantifies blood inside the knee joint.

3. Trial Design

NCT03606109 is recorded as a completed, randomized, parallel-group, Phase 4 study sponsored by NYU Langone Health. The registry lists enrollment as 58 and gives a study start date of 2018-06-26 and primary completion date of 2021-06-02. Masking is recorded as none. These design labels describe the trial as entered in the registry, but the record does not provide enough arm-level detail to establish how randomization connected participants to TXA or a comparison treatment.

The listed intervention is the drug tranexamic acid. The arm names attached to the reported primary outcome are “High Tibial Osteotomy (HTO)” and “Tibial Tubercle Ostetomy (TTO),” and their arm descriptions are blank. The outcome counts are 29.0 for HTO and 26.0 for TTO. Because these labels identify procedures rather than treatment assignments, it is unclear whether the comparison was intended to contrast procedures, treatment allocation within procedures, or something else. The registry record does not report the allocation ratio, treatment schedule, dose, route details beyond the study summary’s reference to intravenous TXA, or the exact control condition.

The registry lists four outcome measures and three secondary outcomes, but reports no analyses in its analysis record. The posted outcome statistics nevertheless include group means and standard deviations for the primary outcome and one detailed secondary outcome, as well as an unadjusted comparison recalculated from the posted summary statistics. No discrepancy is flagged between that recalculation and the posted values. An analysis plan, including any prespecified model, adjustment strategy, or approach to missing observations, is not reported in the registry record. The design labels alone should not be taken as evidence that these details are known.

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

Reasons for not completing this period:

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 Perioperative Blood Loss, measured over Perioperative, up to 2 hours.

The primary endpoint is perioperative blood loss in mL, recorded for the period up to 2 hours. The registry reports this outcome as a mean with a standard deviation for each named group. Blood loss is a continuous measure: it can take a range of values, and the group mean describes its average level while the standard deviation describes variation among observations.

The study summary identifies hemarthrosis—blood accumulating within the knee joint—as a concern motivating the study. The posted primary endpoint is described as perioperative blood loss, not as a direct measurement of blood within the joint. Blood loss may be relevant to a study of bleeding around surgery, but the registry record does not explain how the recorded measure was collected or how it represents hemarthrosis. The record also does not report a more detailed endpoint definition, measurement method, or analysis population for this outcome.

A primary endpoint is generally used to focus the main assessment of a study and to provide a defined outcome for comparing groups. That general role does not resolve the key ambiguity in this record: the reported groups are labeled by osteotomy procedure, while TXA is the listed intervention. The endpoint statistics can be interpreted as a comparison of the HTO and TTO labels, but the registry record does not make clear whether they estimate a TXA treatment contrast.

7. Results Posted in the Registry

• Tibial Tubercle Ostetomy (TTO): mean 56.15 versus 67.80 on control; difference -11.65 (95% CI -36.00 to 12.70), standardized effect d = -0.25; z-test p = 0.348.

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.

Score on Visual Analogue Scale (VAS) for Pain

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Tibial Tubercle Ostetomy (TTO): mean 6.65 versus 7.13 on control; difference -0.48 (95% CI -1.87 to 0.91), standardized effect d = -0.18; z-test p = 0.498.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tibial Tubercle Ostetomy (TTO) and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists VAS pain as a secondary outcome, with three entries carrying the same outcome title. The detailed secondary result describes pain on Day 1. The overall pattern in the posted comparisons is not a clear, precise separation between the named groups: the primary blood-loss interval and the detailed pain interval both include zero. These outcomes measure different things, however, and agreement in the broad direction of estimates does not make one outcome a confirmation of the other.

The pain result is relevant as a patient-reported outcome connected to the study summary’s interest in postoperative pain. It does not directly measure hemarthrosis or blood loss, and it cannot resolve the treatment-assignment ambiguity in the primary comparison. The registry record does not provide enough detail to establish how the secondary entries relate to time points beyond the detailed Day 1 result or whether all planned secondary results are reported.

Unadjusted secondary results generally carry less evidential weight than a clearly prespecified primary analysis because examining multiple outcomes or time points creates more opportunities for chance findings. A multiplicity strategy can control or organize that risk, but none is reported in the registry record. The absence of a reported strategy does not prove that no such plan existed; it means readers cannot assess it from the record. In addition, no sponsor-reported analyses are listed. The secondary results are best treated as descriptive and exploratory rather than as independent confirmation of a TXA effect.

Overall, the secondary outcome adds information about a different postoperative experience, but it does not supply the missing treatment contrast or establish a precise pattern of benefit or harm. Interpretation should remain tied to the group labels actually reported and to the uncertainty in each estimate.

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

• Score on Visual Analogue Scale (VAS) for Pain
• Score on Visual Analogue Scale (VAS) for Pain
• Score on Visual Analogue Scale (VAS) for Pain

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary outcome is continuous and is summarized with a mean and standard deviation. A mean gives the arithmetic average of the measured values in a group. A standard deviation describes how spread out the individual values are around that average. It is not the uncertainty of the mean itself: the standard error, confidence interval, or another inferential measure is needed to describe uncertainty in an estimated group mean or contrast.

What does the mean difference represent?

The reported mean difference is calculated as the TTO group mean minus the HTO group mean. A negative value therefore means that the recorded mean is lower in the group labeled TTO. The estimate is an unadjusted comparison based on posted summary statistics; it does not account for covariates or other design features. No adjusted analysis is reported in the registry record. Moreover, because the groups are identified by procedure labels rather than TXA assignment, the difference is not clearly a treatment effect.

How should the confidence interval be read?

A confidence interval expresses the statistical uncertainty around an estimated contrast under the method’s assumptions. It gives a range of values compatible with the data and calculation, rather than a guarantee that the true value lies in the particular interval. When an interval includes zero, the data do not rule out no difference at the confidence level used. If it also includes values on either side of zero, it is compatible with contrasts in either direction. The interval does not by itself indicate clinical importance, and interpretation depends on how the groups and outcome were defined.

What does the p-value tell us?

The unadjusted p-value is calculated for the contrast using the posted summaries. In general, a p-value describes how unusual data at least as incompatible with a null hypothesis would be if that hypothesis and the calculation assumptions were correct. It is not a measure of the size of an effect, a probability that a result occurred by chance, or a direct measure of clinical relevance. A p-value should be read alongside the effect estimate, confidence interval, study design, and completeness of reporting. Here, no multiplicity adjustment or sponsor-reported analysis is listed.

Why does the group definition matter?

Randomization can support a causal comparison when the randomized groups correspond to clearly defined treatment assignments and the analysis preserves that comparison. The registry records randomization, but the posted arms are named for HTO and TTO, and the arm descriptions are empty. The intervention is TXA, yet the record does not state which arm received it or specify a control treatment. The contrast can therefore be described statistically, but its causal interpretation as a TXA effect is not established by the posted labels.

The record reports group means and standard deviations and contains an unadjusted recalculation of the group difference. Such a recalculation is a simple comparison of the posted summary statistics, not a substitute for a prespecified trial analysis. No analyses are listed in the registry’s analysis record, and no details are reported about covariate adjustment, missing-data handling, or the population included in each analysis. No discrepancy is flagged for the recalculated comparison, but the absence of a discrepancy does not resolve the missing design and analysis details.

For continuous outcomes, group means are useful summaries, but they can conceal differences in distributions, skewness, outliers, or variation across subgroups. The standard deviation helps describe dispersion, but the registry record does not provide individual observations or distributional plots in the registry record used for this explanation. There is no basis in the record to judge whether a normal approximation is appropriate for the primary comparison. The sample-size illustrations use a normal approximation as a planning assumption; that assumption is not evidence about the actual outcome distribution.

In general, over-dispersion matters when observed variability exceeds what a chosen statistical model expects, because standard errors can then be too small and inference overly confident if the model is not adapted. No over-dispersion assessment or model-based analysis is reported for this trial. This general point should not be mistaken for a finding that over-dispersion occurred.

The detailed pain outcome is also continuous and is reported as a mean with a standard deviation. Its unadjusted contrast is a separate analysis from blood loss. When several outcomes or time points are examined, the chance of observing an apparently notable result somewhere among them can increase. Statistical methods may address this multiplicity, but the registry record does not report whether any correction or hierarchical testing strategy was planned or used. The posted secondary result should consequently be treated as exploratory unless further analysis information is available.

These methods describe the statistical meaning of the posted summaries; they do not establish that the outcome definitions, treatment assignments, or analysis choices were prespecified. Those details are not reported in the registry record. The central constraint is interpretive rather than computational: even a correctly calculated difference cannot answer the TXA question if the group labels do not identify treatment allocation.

11. Confidence Intervals and Precision

The primary mean difference is -11.65 mL, with a 95% confidence interval from -36.0 to 12.7 mL. The interval spans zero and includes both a lower mean for TTO and a higher mean for TTO relative to HTO. That breadth means the result is compatible with materially different directions and magnitudes of the group contrast; the estimate should not be treated as a precise measure of the underlying difference.

The interval is a statement about statistical uncertainty under the assumptions of the unadjusted calculation. It does not capture uncertainty about whether the registry’s group labels correspond to TXA assignment, whether blood loss directly represents hemarthrosis, or whether the analyzed observations are complete. Those are design and measurement uncertainties, not reflected by the confidence interval.

The standard deviations also indicate substantial variation in observed blood loss within both named groups: 56.5 mL for HTO and 33.92 mL for TTO. The registry record gives no clinical threshold for an important difference, so statistical precision cannot be translated into a judgment about clinical importance. Nor does an interval containing zero demonstrate equivalence; an equivalence assessment would require a prespecified margin and a design and analysis suited to that question, neither of which is reported in the registry record.

The Day 1 pain comparison likewise has an interval that includes zero. As with the primary result, its uncertainty does not establish that the groups are identical. More fundamentally, neither interval resolves which group received TXA. The numerical precision of an estimate and the validity of its interpretation are separate considerations.

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 illustrations are planning calculations based on the observed effect, not the trial’s original design assumptions. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculations consider detecting the stated fraction of the observed effect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

For continuous outcomes, the listed figures are participants per arm, not a total across both arms. Each 80% power figure describes the planned number of participants in each arm for a hypothetical study with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and assumptions were correct. The 90% power column describes the corresponding planning target for a higher chance of detection. These are prospective design illustrations; they do not indicate the probability that this completed trial detected an effect, and they are not observed power.

The rows scale the effect used for planning: 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. A smaller target effect is harder to distinguish from random variation, so the calculations require more participants per arm to maintain the same planned power. The figures are therefore sensitive to the observed effect used as their starting point. If that estimate is imprecise, the resulting planning illustrations can also be unstable.

These calculations do not repair the ambiguity in the registry’s treatment-group descriptions. They address how many participants per arm might be needed for a hypothetical comparison under the listed assumptions; they do not establish that the trial was designed or analyzed as a TXA-versus-control study. The record does not report its original sample-size rationale, and the planning figures should not be read as evidence about whether enrollment was adequate for the intended clinical question.

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 = -11.650; pooled standard deviation σ = 47.214.
2. n = 2 × (1.96 + 0.842)² × 47.214² / -11.650² = 257.8, rounded up to 258 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 <- -11.65                      # observed difference in means
sigma <- 47.2143166646856                     # 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(3606109)
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 = 258 (80% power), 346 (90% power)
 75% of observed effect: n per arm = 459 (80% power), 614 (90% power)
 50% of observed effect: n per arm = 1,032 (80% power), 1,381 (90% power)
power.t.test: 258.8 
Simulated power at n = 258 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 record lists a primary outcome and three secondary outcomes, with the secondary outcome title “Score on Visual Analogue Scale (VAS) for Pain” repeated. Multiple outcomes and time points raise a multiplicity question: when more than one statistical comparison is made, the chance of at least one apparently unusual result can increase even if there is no underlying effect. Common approaches include adjusting significance thresholds, defining a hierarchy of outcomes, or designating secondary analyses as exploratory. The record does not report whether any such approach was prespecified or used.

The registry’s analysis record contains no reported analyses. The posted summaries include unadjusted comparisons, but no multiplicity-adjusted results or explanation of a testing strategy is reported. The unadjusted secondary results should therefore be interpreted cautiously and should not be treated as confirmatory evidence. The record does not report whether additional outcomes or time points were planned but omitted from the results.

Missing-data handling is also not reported in the registry record. The posted primary outcome counts are 29.0 for HTO and 26.0 for TTO, while adverse-event denominators are 31 and 27. These figures refer to different reported outcome contexts and cannot be reconciled from the available information. The record does not state why counts differ, whether observations were missing, how missingness was defined, or whether any imputation or sensitivity analysis was used.

The analysis population is not described in enough detail to determine whether results follow an intention-to-treat approach, a per-protocol approach, or another rule. The registry’s randomized designation does not by itself specify which participants were included in each outcome analysis. The record also does not report an analysis plan, covariate adjustment, or handling of protocol deviations. These omissions limit assessment of bias and reproducibility, particularly because the posted arm labels do not clearly identify randomized treatment assignment.

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.

The registry reports zero serious adverse events in the HTO group and zero in the TTO group. It also reports zero other adverse events in both groups and zero deaths in each. The denominators listed for the adverse-event summaries are 31 for HTO and 27 for TTO. These are the registry’s reported at-risk counts for those summaries; they differ from the outcome counts attached to the blood-loss results, and the record does not explain the difference.

These figures mean that no events were recorded in the reported categories and denominators. They do not prove that no adverse events occurred outside the definitions, observation period, or reporting process used for the registry, and they do not establish that TXA was safe or unsafe. The registry record does not provide event definitions, follow-up details, or a treatment-specific safety comparison. Because the groups are labeled by procedure rather than TXA assignment, the figures cannot be confidently attributed to TXA exposure.

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

The posted results give descriptive information about perioperative blood loss and Day 1 pain in groups labeled HTO and TTO. For blood loss, the estimated mean difference is uncertain: its confidence interval includes zero and values in either direction. The detailed pain comparison is similarly not precise enough to establish a clear group difference. These findings describe what the posted data show; they do not demonstrate that the groups are equivalent.

Most importantly, the registry record does not clearly map the reported groups to TXA treatment assignment. TXA is listed as the intervention, but the outcome groups are named for osteotomy procedures and their descriptions are blank. The record does not state which participants received TXA or what served as a control. Therefore, the posted contrasts cannot be interpreted confidently as the causal effect of TXA, even though randomization is recorded.

The primary outcome is perioperative blood loss up to 2 hours, not a clearly defined direct measure of hemarthrosis in the posted details. The record does not describe the measurement procedure or explain how blood loss represents blood within the knee joint. It also does not report a clinical threshold for an important difference. Consequently, the results cannot establish whether a difference matters clinically or whether the endpoint captures the specific condition motivating the study.

The adverse-event summaries report no recorded serious events, other events, or deaths in the listed groups. Those counts do not establish the absence of risk, and the treatment assignments and event ascertainment details are not clear enough to support a TXA-specific safety conclusion. Likewise, the sample-size illustrations are hypothetical planning calculations, not evidence of the study’s original design adequacy or its ability to detect an effect.

In sum, the registry record permits a cautious description of the observed group summaries and their statistical uncertainty. It does not support a firm conclusion about TXA’s effects on hemarthrosis, blood loss, pain, or safety because the treatment contrast and several measurement and analysis details are not reported clearly.

17. Why This Trial Matters Statistically

This trial record illustrates why statistical interpretation depends on the connection between an estimand—the effect a study aims to assess—and the groups actually analyzed. A randomized label is useful, but it is not enough on its own. Readers need to know which treatment each group received and what the comparison condition was. Here, TXA is listed as the intervention, while the outcome groups are labeled HTO and TTO. Without an explicit mapping, the numerical contrast cannot be confidently interpreted as a TXA effect.

The record also distinguishes a motivating clinical concept from the measured endpoint. The study summary focuses on hemarthrosis, whereas the posted primary outcome is perioperative blood loss in mL up to 2 hours. A related measure may be informative, but its relevance depends on how it was collected and how closely it represents the target concept. That measurement link is not described in the registry record.

Finally, the confidence interval adds context that a point estimate or p-value alone cannot provide. The interval spans zero and includes differences in either direction, so the posted result is imprecise. This does not prove no effect; it limits what can be concluded from the data. The record’s missing analysis, multiplicity, and missing-data details further constrain evaluation. These are general lessons in trial reporting: clear treatment labels, outcome definitions, and analysis methods are essential for judging both what a result estimates and how much confidence it warrants.

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.

A key limitation specific to this record is the mismatch between the stated intervention and the posted arm labels. TXA is listed as the intervention, yet the reported groups are HTO and TTO, with blank arm descriptions. The registry record does not establish which group received TXA, whether both did, or what comparison treatment was used. This prevents a clear treatment-effect interpretation of the reported differences.

The primary endpoint is perioperative blood loss up to 2 hours. The registry summary describes an aim related to hemarthrosis, pain, and swelling, but the record does not explain how blood loss was measured or how it serves as a measure of hemarthrosis. Detailed endpoint description and analysis population are not reported. The record also does not report a threshold for clinical importance, so the practical meaning of the estimated difference cannot be assessed from the posted statistics alone.

Other important details are absent: allocation ratio, treatment schedule and dose, control condition, original sample-size justification, analysis plan, multiplicity approach, missing-data handling, and the rule defining the analysis population. No analyses are listed in the registry analysis record. The reported outcome counts and adverse-event denominators differ, and the record does not explain why. These omissions limit assessment of bias, precision, and reproducibility.

The trial is recorded as unmasked. The registry does not describe safeguards against measurement or assessment bias, and the endpoint measurement method is not reported. The adverse-event counts are also limited by the absence of event definitions and follow-up details. These limitations do not show that the study was conducted improperly; they identify what cannot be evaluated from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Reducing Hemarthrosis in Tibial Tubercle Osteotomy by the Administration of Intravenous Tranexamic Acid — NCT03606109.
• Registry record last updated 2022-09-21; status last verified 2022-08.
• Results first posted 2022-09-21.
• 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

NCT03606109 is a completed, randomized, parallel-group, unmasked Phase 4 study sponsored by NYU Langone Health. It lists intravenous tranexamic acid as the intervention and concerns HTO and TTO. The primary outcome is mean perioperative blood loss in mL up to 2 hours. The posted comparison gives an unadjusted mean difference of -11.65 mL for TTO relative to HTO, with a 95% confidence interval from -36.0 to 12.7 mL.

The record’s treatment interpretation is limited because the reported arms are labeled by procedure, not by TXA assignment, and their descriptions are blank. The registry does not report analyses in its analysis record or clarify the analysis plan, missing-data handling, or multiplicity strategy. A detailed secondary outcome concerns Day 1 VAS pain. The adverse-event summaries record zero serious events, zero other events, and zero deaths in the named groups, with denominators of 31 and 27. Overall, the posted statistics describe group differences but do not clearly establish a TXA-versus-control effect.