Randomized Controlled Trial of Tranexamic Acid in Total Knee Arthroplasty: Intravenous vs. Topical: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Controlled Trial of Tranexamic Acid in Total Knee Arthroplasty: Intravenous vs. Topical (NCT01940523), a randomized phase 4 study. The primary outcome is Total Blood Loss.

2. Clinical Question

The comparison is between two ways of administering the same drug in the setting of unilateral total knee replacement. It is not a comparison with no tranexamic acid or with a placebo. The treatment groups therefore address the relative results of topical and intravenous administration under the trial conditions described in the registry. The registry lists drain output and the number of participants requiring transfusion as secondary outcomes, alongside the primary blood-loss measure.

The summary states that the investigators hypothesized the two routes would be equally good at reducing blood loss and transfusion need. That stated hypothesis gives context for interpreting a difference between groups, but the registry record does not report a prespecified equivalence or noninferiority margin. It also does not report enough detail to determine whether the statistical design formally tested equivalence. A difference estimate and its confidence interval describe the observed contrast; they do not, by themselves, establish equivalence.

3. Trial Design

This was a randomized, parallel-group phase 4 trial comparing topical with intravenous tranexamic acid in total knee arthroplasty. The registry lists triple masking, but does not identify which groups of people were masked or describe how masking was maintained. Allocation was randomized; details of sequence generation, concealment, and implementation are not reported in the registry record. The study status is completed, and enrollment is listed as 640.

Each group included 320 participants in the posted primary outcome results. One group received topical tranexamic acid, and the other received intravenous tranexamic acid. The registry describes the intravenous regimen as two 1g doses at specified stages of the operation. It describes a topical solution containing 3g in 75mL, mixed in the operating room. The available topical administration description ends before the full procedure is stated, so further details are not reported in the registry record.

The primary outcome was total blood loss, measured in milliliters and summarized as a mean with standard deviation. Its listed timeframe is during surgery, while the description says the estimate uses the difference between hematocrit measured before and after surgery. Drain output was a continuous secondary outcome measured from the end of surgery to 24 hours postoperatively. The other secondary outcome counted participants requiring transfusion over the hospital stay, described as averaging three days.

The registry lists a start date of 2013-05 and a primary completion date of 2015-12-28. The sponsor is Hospital for Special Surgery, New York. The registry does not report the original sample-size justification, a detailed statistical analysis plan, or whether interim analyses were planned or conducted. The posted results include group summaries and comparisons, but the registry does not report outcome-specific analysis methods or analysis populations.

Randomization supports a between-group comparison, but the interpretation still depends on how participants were analyzed, how missing outcomes were handled, and whether the reported estimates followed the planned analysis. Those details are not reported in the registry record. The posted group sizes and outcome summaries describe the available results; they do not establish by themselves whether every randomized participant contributed to every analysis.

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 Total Blood Loss, measured over during surgery.

The primary endpoint was total blood loss, expressed in milliliters. The registry describes it as an estimate based on the participant’s blood volume, calculated from height and weight, multiplied by the change in hematocrit after surgery compared with the preoperative value. This is a derived measure rather than a direct collection of all blood lost. The registry does not provide further technical detail about the formula or the timing of the hematocrit measurements.

Blood loss is used in this trial because the study question concerns bleeding associated with surgery and whether its measured amount differs between the two administration routes. A continuous outcome preserves information about the amount measured for each participant, rather than reducing the outcome to a yes-or-no event. The posted results summarize the measure with a group mean and standard deviation. The mean describes the average estimated blood loss in each group; the standard deviation describes variation among participant measurements within a group.

The registry labels the primary outcome timeframe as during surgery, although its definition relies on a change in hematocrit after surgery. That distinction matters when understanding what the endpoint represents: it is a calculated estimate linked to perioperative blood loss, not simply blood collected during the operation. It is also distinct from drain output, which was recorded over a postoperative interval, and from transfusion, which was counted as a participant-level event during the hospital stay.

The measure can support a comparison of group averages, but its clinical interpretation depends on the validity and consistency of the estimation procedure. The registry record does not report validation details, missing measurement handling, or a threshold defining a clinically important difference. Statistical evidence about a difference in means therefore does not on its own establish the practical importance of that difference.

7. Results Posted in the Registry

• Intravenous Tranexamic Acid: mean 271.22 versus 323.59 on control; difference -52.37 (95% CI -88.78 to -15.96), standardized effect d = -0.22; z-test p = 0.005.

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.

Drain Output

• 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:
  • Intravenous Tranexamic Acid: mean 456.22 versus 560.13 on control; difference -103.91 (95% CI -148.30 to -59.52), standardized effect d = -0.36; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Intravenous Tranexamic Acid than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The Number Patients Requiring a Transfusion

• 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:
  • Topical TXA Group: 1.9% (6/320) versus 0.6% (2/320) on control; risk difference 1.2 percentage points (95% CI -0.5 to 3.0), risk ratio 3.00 (0.61–14.75); unadjusted two-proportion z-test p = 0.155.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Topical TXA Group and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes give related but not identical perspectives on bleeding and its consequences. Drain output is a postoperative measurement of fluid collected over a defined interval, while transfusion records whether a participant received a transfusion during the hospital stay. Neither outcome is the same construct as estimated total blood loss during surgery. They can add context to the primary result, but they cannot be treated as interchangeable measures.

At the broad level, the posted drain-output comparison has a pattern aligned with the primary mean comparison, whereas the transfusion comparison is less conclusive. This combination is not inherently contradictory. A continuous measure can detect a shift in average amount without a corresponding clear difference in a comparatively uncommon event. Transfusion decisions can also reflect clinical practices and factors beyond a measured blood-loss estimate; the registry does not describe those decision processes.

Secondary outcomes generally carry less weight than the primary outcome when they are not the principal focus of the study. The registry does not report whether the secondary outcomes were prespecified in a detailed analysis plan, whether all planned outcomes were posted, or whether testing was adjusted for multiplicity. When several outcomes are examined, the chance of observing a seemingly notable result among them can increase. Unadjusted secondary p-values should therefore be interpreted cautiously and alongside the estimates and confidence intervals, not as standalone proof.

The secondary findings may help assess whether the primary pattern is accompanied by related outcome patterns, but they do not establish a mechanism or prove that one outcome mediates another. The registry does not report individual-level relationships among blood loss, drain output, and transfusion. Nor does it report additional analyses that would connect these endpoints. The reasonable reading is that they provide complementary descriptive and comparative evidence with different levels of precision, rather than a single unified measure of treatment effect.

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

• Drain Output
• The Number Patients Requiring a Transfusion

9. Statistical Interpretation

10. Statistical Methods Explained

The main comparison is a difference between group means for a continuous outcome. For total blood loss, the registry reports a mean and standard deviation for each treatment group, then gives a mean difference comparing intravenous with topical administration. The sign of a difference depends on the order of subtraction. In this comparison, a negative value means the posted mean is lower in the intravenous group than in the topical group. The unit remains milliliters, so the estimate is interpretable in the original measurement scale.

What does a standard deviation describe?

A standard deviation describes how spread out individual measurements are around their group mean. It is not the uncertainty of the mean itself and is not a confidence interval. A large standard deviation relative to the mean difference indicates that individual outcomes vary substantially compared with the average contrast. In the primary results, the group standard deviations are 255.9 and 212.1 ml, and the pooled standard deviation listed for the comparison is 235.0 ml. These summaries describe the observed distributions but do not show their full shape or whether unusual values strongly influence the means.

What does a confidence interval add?

A confidence interval places uncertainty around an estimate. For the primary mean difference, the reported interval runs from -88.78 to -15.96 ml. Under the method’s assumptions, the interval indicates a range of effect values compatible with the observed data. It does not mean that a particular interval has a probability of containing the true value, and it does not incorporate every possible source of uncertainty, such as measurement error, bias, or departures from the analysis assumptions. The registry does not report the detailed method used to calculate these intervals.

How should the p-value be read?

A p-value assesses how unusual data at least as inconsistent with a null hypothesis would be if that hypothesis and the analysis assumptions held. It is not a measure of clinical importance and is not the probability that the result occurred by chance. The primary comparison has an unadjusted p-value of 0.005. The word unadjusted indicates that the posted value is not reported as corrected for multiple comparisons. The registry does not report whether any other testing strategy was planned.

For drain output, the comparison is again a difference in means, with intravenous administration as the compared group and topical administration as the reference. The reported difference is -103.9 ml, with a confidence interval from -148.3 to -59.52 ml. The posted standard deviations are 297.2 ml for topical and 275.4 ml for intravenous administration. As with the primary outcome, the estimate describes a difference in group averages, not a guarantee about an individual participant’s outcome.

The transfusion outcome is binary at the participant level: a participant either required a transfusion during the stated hospital-stay period or did not. The registry reports counts and a risk difference. The risk difference is the difference between the proportions in the two groups, expressed in the reported scale; it is not a difference in the total number of units transfused. The comparison is topical versus intravenous, and the reported estimate is 0.013 with a confidence interval from -0.005 to 0.030. Because this interval includes zero, the estimate is compatible with no risk difference as well as with differences in either direction under the interval’s assumptions.

The registry also lists a relative risk and an odds ratio for the transfusion comparison. Relative measures compare event frequency across groups using a ratio rather than a subtraction. When events are sparse, such estimates can be unstable and their intervals can be wide. The registry does not report a separate adjusted model or analysis method for these relative measures, so the main interpretation should remain anchored in the posted counts, risk difference, and its interval.

Why can outcome type affect precision?

Continuous measurements use information from the magnitude of each observed value. A binary outcome uses whether an event occurred, and the amount of information depends substantially on the number of events. With few events, the estimated group contrast can remain uncertain even when the overall groups are sizable. That general statistical feature helps explain why the transfusion comparison may be less precise than a continuous outcome comparison; it is not evidence that one outcome is more important than another.

The standardized mean difference listed for the primary comparison is -0.223. A standardized effect expresses a mean contrast relative to a standard deviation, making it dimensionless; it is less directly interpretable in the original clinical units than the mean difference. Standardized values can help with planning illustrations, but do not replace the milliliter estimate or establish clinical importance. No standardized effect is needed to understand the direction of the original-scale result.

The registry reports no outcome-specific analyses in its analysis listings. It does not describe covariate adjustment, missing-data methods, analysis populations, or any model diagnostics. Consequently, it is not possible from the registry record to determine whether the posted comparisons reflect an intention-to-treat analysis, a per-protocol analysis, or another approach. The group summaries and contrasts can still be described, but the unreported analysis details limit assessment of how robustly the results address the randomized comparison.

11. Confidence Intervals and Precision

Precision is the degree to which an estimate is concentrated around a range of plausible values. Confidence intervals are useful for assessing precision because they display uncertainty around an estimate in the same units or scale as the outcome. For the primary mean difference, the estimate is -52.37 ml and the 95% confidence interval ranges from -88.78 to -15.96 ml. The interval lies below zero, indicating that the reported comparison favors a lower mean in the intravenous group, while also showing uncertainty about the size of that difference.

The interval does not identify a single true value, and its endpoints are not guaranteed limits on the effect. Its interpretation relies on the method and assumptions used to calculate it. The registry does not report details of that calculation or a threshold for a clinically important difference. It is therefore possible to describe the statistical direction and range without claiming that all values in the interval have the same practical significance.

The drain-output interval, from -148.3 to -59.52 ml, is also entirely below zero. The transfusion risk-difference interval, from -0.005 to 0.030, crosses zero. This contrast in interval position reflects different evidence in the posted comparisons, but interval width and location should be considered together. For an outcome with few events, a range that spans both directions can signal that the estimate does not pin down the direction precisely.

Confidence intervals account for sampling variation under the chosen analysis; they do not correct for potential bias, measurement limitations, selective reporting, or unrecorded departures from the protocol. The registry does not report missing-data details, the analysis population, or multiplicity handling. Those omissions mean that the posted intervals should be read as precision measures for the reported comparisons, not as complete measures of all uncertainty surrounding the findings.

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 planning figures are illustrations based on the observed effect, not the trial’s original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two groups, a normal approximation, and detection of the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

For these non-time-to-event outcomes, the figures are participants per arm, not the total across both groups. The 80% power column describes the approximate per-arm sample size that, under the stated assumptions, would give an 80% chance of detecting the chosen effect if that effect were the true one. The 90% power column uses a higher chance of detection and therefore generally requires more participants per arm for the same effect. These are design-planning concepts, not guarantees about what a future study would find.

The listed planning scenarios use 100%, 75%, and 50% of the observed effect. As the assumed effect becomes smaller, the planning requirements increase: a smaller difference is harder to distinguish from random variation, so more participants are generally needed to achieve the same target power. The required sample also depends on the outcome and its variability or event frequency; the planning figures differ between continuous measures and the transfusion outcome.

These values are not observed power. They do not measure the probability that the completed trial’s finding is true, and they do not retrospectively prove that the trial was adequately designed. They are conditional illustrations calculated from the observed effect and stated planning assumptions. The registry’s own sample-size rationale is not reported, so the illustrations should not be treated as evidence about what the investigators planned before enrollment.

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 = -52.370; pooled standard deviation σ = 234.999.
2. n = 2 × (1.96 + 0.842)² × 234.999² / -52.370² = 316.1, rounded up to 317 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 <- -52.3699999999999                      # observed difference in means
sigma <- 234.999080530116                     # 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(1940523)
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 = 317 (80% power), 424 (90% power)
 75% of observed effect: n per arm = 562 (80% power), 753 (90% power)
 50% of observed effect: n per arm = 1,265 (80% power), 1,693 (90% power)
power.t.test: 317 
Simulated power at n = 317 per arm: 0.798 (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

Multiplicity arises when several outcomes, comparisons, or analyses are tested. If each test is considered separately without adjustment, the chance of at least one small p-value across a collection of tests can be higher than the chance for a single test. This is a general statistical consideration, not a claim that the trial’s results are false. The registry reports one primary outcome and two secondary outcomes, but does not report whether the investigators planned an adjustment for multiple testing, a hierarchy of tests, or another approach to controlling the overall error rate.

The posted p-values are described as unadjusted. The primary comparison’s p-value can be interpreted as the reported evidence for that comparison under its own test, but it should not be read as accounting for the full set of outcomes or any additional analyses. The record does not report the full set of analyses undertaken, so the extent of multiplicity cannot be determined from the posted information.

Missing-data handling is also not reported in the registry record. The group summaries show 320 participants in each group, but that does not establish that all randomized participants had complete data for every endpoint. The registry does not state whether participants withdrew, whether outcomes were unavailable, how missing values were handled, or whether sensitivity analyses were performed. The absence of a reported missing-data method is a limit on evaluating the robustness of the estimates, rather than evidence that data were missing.

The analysis populations are not reported. In particular, the record does not identify whether the results use all randomized participants, only participants who received their assigned treatment, or another defined population. It also does not report whether participants were analyzed according to randomized assignment. This matters because exclusions or departures from assigned treatment can affect the meaning of a randomized comparison.

Details such as interim analyses, stopping rules, and a prespecified statistical analysis plan are not reported in the registry record. These should not be inferred from the phase, masking label, or completed status. Without those details, readers can describe the posted estimates and their uncertainty, while recognizing that multiplicity control, missingness, and analysis-population choices cannot be independently assessed from the registry results.

15. 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.

The registry records zero serious adverse events affecting participants in each group and zero other adverse events affecting participants in each group. Each group lists 320 participants at risk for these event categories. These are the posted event summaries and should be read as registry-reported counts, not as proof that no adverse events of any kind occurred outside the recorded categories or reporting period.

Death counts are not reported in the registry record. A missing death count should not be interpreted as zero. The registry also lists no serious adverse event terms, which means no specific serious-event terms appear in the posted results; it does not provide additional detail on event definitions, surveillance procedures, or the period of safety follow-up.

These summaries are limited for comparing safety. A zero count in both groups does not establish that the treatments have identical safety profiles, and the record does not report confidence intervals or a formal safety comparison. The adverse-event information is descriptive and should be interpreted within the scope and completeness of the registry reporting.

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

The posted results support a statistical distinction between the group means for the primary blood-loss estimate: the intravenous group had a lower reported mean, and the confidence interval for the mean difference lies below zero. The drain-output comparison has a similar direction. These statements describe the trial’s posted data and do not by themselves establish how important the differences are in practice.

The registry summary frames the study around whether topical and intravenous administration would be equally good at reducing blood loss and transfusion need. However, no equivalence or noninferiority margin is reported. A failure to find a statistically clear difference would not establish equivalence, and a statistically detectable difference does not automatically identify a meaningful advantage. Formal equivalence claims require a prespecified margin and a design and analysis suited to that question; those details are not reported in the registry record.

The transfusion outcome does not show a statistically clear risk difference in the posted unadjusted comparison. Its interval spans zero, leaving uncertainty about whether the groups differ and in which direction. That finding does not prove that the groups are the same. The number of transfusion events and the lack of a reported analysis plan limit how strongly this endpoint can resolve the study’s broader question.

The findings are specific to the trial population, procedures, regimens, and outcome definitions represented in the record. Eligibility criteria beyond the condition and procedure context, participant characteristics, adherence, and details of the full topical protocol are not reported. The registry results do not establish effects in other settings or populations, and they do not provide a basis for individual treatment decisions.

Finally, the registry’s statistical results address group-level comparisons. They do not predict an individual participant’s blood loss, drain output, or transfusion requirement. The absence of reported adverse events in the listed categories also does not prove an absence of risk. A careful reading keeps the observed estimates, statistical uncertainty, clinical importance, and limits of registry reporting distinct.

17. Why This Trial Matters Statistically

This trial is statistically informative because it compares two active administration routes within a randomized parallel-group design, rather than comparing treatment with no treatment. That makes the central contrast one of relative results between topical and intravenous use. Understanding the contrast depends on keeping the direction of subtraction clear and distinguishing the outcome scales: the primary and drain measures are continuous, while transfusion is a participant-level event.

The study also illustrates why a primary endpoint and related secondary endpoints may not tell exactly the same story. Estimated blood loss and drain output summarize quantities, while transfusion is an event with a different frequency and clinical context. The continuous comparisons can show a pattern in group averages even when the event comparison remains uncertain. Treating these endpoints as complementary, rather than interchangeable, avoids over-reading agreement or disagreement among them.

Precision is central to interpretation. The primary confidence interval excludes zero, but still spans a range of possible mean differences. The transfusion interval includes zero and permits uncertainty about the direction of the risk difference. Looking at the estimates and intervals, rather than relying only on whether a p-value crosses a conventional threshold, gives a more complete account of what the posted results can support.

The record also demonstrates the value of transparent reporting. Information about the original sample-size rationale, analysis populations, missing data, multiplicity, and detailed statistical methods is not reported. These omissions do not invalidate the posted summaries, but they constrain assessment of how closely the analyses followed the intended design and how robust the results are to analytic choices. Statistical interpretation is strongest when numerical findings are considered together with these reporting limits.

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.

Several trial-specific limitations follow from what the registry does and does not report. The description of topical administration is incomplete, ending during the account of how the solution was applied. The full administration procedure therefore cannot be reconstructed from the registry record. The intravenous regimen is described in more detail, but further information about adherence to either regimen is not reported.

The primary outcome is an estimate based on blood volume and postoperative versus preoperative hematocrit, rather than a direct measure of all blood lost. The record does not provide the exact calculation details, measurement timing, validation information, or missing-measurement procedures. Although the outcome timeframe is labeled during surgery, its description uses a postoperative hematocrit. This makes the precise measurement window and interpretation dependent on details not reported in the registry record.

Participant eligibility criteria and baseline characteristics are not reported in the registry record from the registry record. It is therefore not possible to assess how closely the randomized groups were balanced on measured characteristics or how broadly the findings may apply. The record also does not identify the exact people masked under the triple-masking label or explain how masking was implemented.

The registry does not report the sample-size justification, a detailed analysis plan, the analysis populations, missing-data handling, or multiplicity procedures. These omissions matter particularly for the secondary outcomes and for understanding whether all randomized participants contributed to each comparison. The posted summaries and estimates remain interpretable as reported results, but these gaps limit independent assessment of analysis robustness and completeness.

Safety reporting is also limited: event counts are posted for serious and other adverse events, but death counts are not reported, and definitions and follow-up details are absent. The record does not provide enough information to infer a complete safety profile from the listed counts alone.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Randomized Controlled Trial of Tranexamic Acid in Total Knee Arthroplasty: Intravenous vs. Topical — NCT01940523.
• Registry record last updated 2019-11-27; status last verified 2019-11.
• Results first posted 2017-06-14.
• 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

The registry record describes a completed phase 4 randomized parallel-group trial of topical versus intravenous tranexamic acid during unilateral total knee arthroplasty for osteoarthritis. It lists triple masking and enrollment of 640 participants. The sponsor is Hospital for Special Surgery, New York; the listed study start is 2013-05 and primary completion date is 2015-12-28.

The primary endpoint was estimated total blood loss in milliliters. Posted results show a lower group mean for intravenous administration, with a reported mean difference of -52.37 ml and a 95% confidence interval from -88.78 to -15.96 ml. Drain output showed a similarly directed comparison; the transfusion comparison was less conclusive. The registry also reports zero serious and zero other adverse events affecting participants in each group, while death counts are not reported.

The record does not report the original sample-size rationale, detailed analysis plan, analysis populations, missing-data methods, or multiplicity procedures. These limits should accompany interpretation of the posted estimates.