Tranexamic Acid Dosing for Major Joint Replacement Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tranexamic Acid Dosing for Major Joint Replacement Surgery (NCT05075200), a non-randomized phase 2 study. The primary outcome is Blood Plasma TXA Concentration - Total Body Clearance.

2. Clinical Question

3. Trial Design

The registry record identifies this as a phase 2 study of tranexamic acid dosing for major joint replacement surgery. The listed conditions are knee and hip replacement. It is described as a parallel study with non-randomized allocation and no masking. The record lists enrollment of 21 and a completed status. It names Sunnybrook Health Sciences Centre as sponsor, with a start date of 2021-12-14 and a primary completion date of 2022-10-26.

The two groups are defined by kidney function rather than randomized assignment. Group I includes participants with glomerular filtration rate below 60 mL/min/1.73m2 and participants on dialysis. Group II includes participants with glomerular filtration rate at least 60 mL/min/1.73m2. The record does not describe a randomized comparison, and these group definitions mean that differences between groups could reflect kidney function or other group characteristics, not only differences in drug handling.

The study description says TXA is given after anesthesia and describes a hospital standard dose of 20mg/kg, with a lower dose for people with kidney problems and lower kidney function. It does not state the exact reduced dose or provide a complete dose schedule for each group. Blood samples were collected at 5/15/30/60/90/180/360/540 minutes after bolus, according to the primary outcome description. The brief summary also describes samples taken through an IV line during and after surgery.

The record lists 11 outcome measures and 0 analyses. It names intraoperative blood loss and transfusion, hemoglobin change, postoperative creatinine and eGFR, in-hospital mortality, and hospital length of stay among secondary outcomes. Numerical results for these outcomes, details of the analysis population, and a statistical analysis plan 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 Blood Plasma TXA Concentration - Total Body Clearance, measured over Collected at 5/15/30/60/90/180/360/540 minutes after bolus.

The primary endpoint is blood plasma TXA concentration—total body clearance, measured in mL/min. Clearance is a pharmacokinetic quantity used to describe how quickly a drug is removed from the body relative to its concentration in the measured fluid. It is not itself a direct measure of bleeding, transfusion, or another clinical outcome.

The registry record describes serial measurement of plasma TXA concentration at 5/15/30/60/90/180/360/540 minutes after a bolus. Those concentration measurements were processed using curve-stripping according to a 2-compartment model. The model produced a single total body clearance value for each participant, and those participant-level values were then averaged. The listed summary measure is a mean, with standard deviation as the dispersion measure.

Pharmacokinetic measurements can help characterize how drug exposure changes over time and can inform the development of dosing regimens. In this study, the stated purpose of the concentration measurements was to build a pharmacokinetic model and dosing regimens for the two kidney-function groups. That is the rationale for measuring clearance rather than relying only on an immediate surgical outcome.

The registry record does not report the mean clearance in either group, the standard deviations, or a between-group estimate. It also does not report the participant-level data or the fitted model details beyond the stated 2-compartment approach. As a result, the endpoint’s definition and collection schedule can be described, but its numerical findings and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary measure summarized as a mean and standard deviation. The endpoint is each participant’s estimated total body clearance of TXA, derived from a series of plasma concentration measurements. The stated analysis then averages participant-level clearance values. The numerical results and the inferential method used to compare groups are not reported in the registry record.

What does a mean describe?

A mean is a measure of the center of a set of values. In this study, the values being averaged are participant-level clearance estimates, not the serial concentration readings themselves. A group mean gives a concise description of typical clearance in that group, but it does not show how individual participants’ values vary. It can also be influenced by unusually high or low values. The registry record identifies the mean as the parameter but does not give the group estimates, so the observed center cannot be assessed.

What does standard deviation describe?

Standard deviation describes the spread of participant-level values around their mean. It is not the same as a confidence interval: standard deviation describes variation among the observed values, whereas a confidence interval expresses uncertainty about an estimated quantity. Both can be useful, but they answer different questions. The record names standard deviation as the dispersion measure and does not report its value for either group. It also does not report a confidence interval for the mean or for a between-group contrast.

How should a confidence interval be read?

In general, a confidence interval represents uncertainty around an estimate under the assumptions of the statistical method used. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. The interval’s interpretation depends on the analysis and its assumptions; it does not establish that a result is clinically important or that a causal effect has been identified. No confidence interval for the primary endpoint is reported in the registry record, so the precision of the clearance estimates or any comparison cannot be judged.

What does the pharmacokinetic model do?

The primary description says that serial plasma concentration data were processed by curve-stripping according to a 2-compartment model. In general, a compartment model represents the movement of a drug through simplified connected spaces in the body. A model can use measurements over time to characterize the concentration curve and derive quantities such as clearance. This is a way to summarize a complex time course, not a direct measurement of every process in the body. The quality of the derived estimate depends on the collected measurements, model assumptions, and fit to the data. The registry record does not report model diagnostics, alternative models, or sensitivity analyses.

The listed collection schedule is 5/15/30/60/90/180/360/540 minutes after bolus. Repeated measurements allow the concentration’s change over time to be observed rather than relying on a single blood sample. The record says the concentration data were used to calculate one value per participant before averaging. It does not report whether all scheduled samples were available for every participant, how missing samples were handled, or whether any participant-level clearance values could not be estimated.

Why does over-dispersion matter?

In general, over-dispersion means that observed variation is greater than a statistical model expects. It matters when the analysis assumes a particular degree of variability: underestimated variation can make uncertainty appear smaller than it is. The primary measure in this record is continuous, and the registry specifies a mean and standard deviation; it does not report a model for count data or an over-dispersion assessment. No finding about over-dispersion can be made from the registry record. More generally, methods should reflect the distribution and spread of the data rather than treating a model assumption as automatically satisfied.

What can be inferred from a non-randomized comparison?

Random assignment is one way to make comparison groups more similar, on average, with respect to factors other than the intervention. This study is explicitly identified as non-randomized, and the groups are defined by kidney function. A comparison between these groups would therefore describe observed differences in the enrolled participants. It would not, by itself, isolate a causal effect of a dosing strategy. Statistical adjustment can sometimes address measured differences, but the registry record does not report an adjusted analysis or the variables that would have been included.

The record’s sample-size assumptions describe a planning illustration computed from the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustration is described as considering a stated fraction of the observed effect. These assumptions are planning conventions, not evidence that the study had a particular probability of detecting an effect. Any sample-size figures of this kind are planning illustrations, never observed power. The numerical effect and numerical planning results are not reported in the registry record, so no such values can be interpreted.

The registry record does not report a statistical analysis plan, the test used for the primary endpoint, any adjustment for covariates, or an inferential comparison. It lists 0 analyses. Accordingly, explanations of means, standard deviations, models, and confidence intervals are general statistical context; they should not be mistaken for additional methods or results reported for this study.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("Group I", "Group II")
n   <- c(10, 11)
m   <- c(58, 116)
sp  <- c(21, 23.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Group I  10  58.000  21.000  42.978  73.022
CARM  Group II  11  116.000  23.900  99.944  132.056

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 11 outcome measures, including the primary TXA total body clearance measure and secondary outcomes related to blood loss and transfusion, hemoglobin, kidney-function measures, mortality, and hospital length of stay. It lists 0 analyses. The record does not report which outcomes were analyzed, which were designated as secondary or exploratory in a statistical plan, or whether any formal hypothesis tests were performed.

When several outcomes or comparisons are examined, the chance of finding at least one apparently notable result by chance can increase. General statistical approaches to multiplicity include defining a primary comparison in advance, adjusting inferential thresholds, or clearly labeling additional analyses as exploratory. The registry record does not report a multiplicity strategy. It is therefore not possible to determine whether or how the study addressed multiplicity.

Missing-data handling is also not reported in the registry record. The primary endpoint depends on serial plasma concentration measurements and a participant-level model-derived clearance estimate. The record does not state whether all scheduled samples were collected for every participant, how incomplete concentration profiles were treated, or how missing outcome values were handled. It does not report a missingness summary or sensitivity analysis.

The analysis population is not reported in the registry record. The listed enrollment is 21, but the record does not specify how many participants contributed to each primary analysis or whether exclusions occurred after enrollment. It also does not describe whether all enrolled participants were included in outcome summaries. Without this information, the relationship between enrollment and the analyzed data cannot be assessed.

12. 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 adverse-event fields list Group I with 10 at risk and 0 serious adverse events, 0 other adverse events, and 0 deaths. Group II is listed with 11 at risk and 0 serious adverse events, 0 other adverse events, and 0 deaths. No top serious adverse-event terms are listed. These figures describe the entries in the registry record; they are not a detailed narrative of safety monitoring.

A zero count means no events were recorded in that field for the listed group. It does not prove that the true risk is zero, and it does not establish that the groups have the same risk. With limited group counts, uncommon events may not appear in the observed record. The registry record does not report the event definitions, the duration or completeness of safety follow-up, or a formal between-group safety analysis.

The listed counts should also be kept distinct from the study’s primary pharmacokinetic endpoint. They do not provide evidence about TXA clearance, blood loss, transfusion, or other secondary outcomes. No medical conclusion about safety should be drawn from these adverse-event entries alone.

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

This study addresses a pharmacokinetic question in the context of hip and knee replacement: how TXA total body clearance is characterized in groups defined by kidney function. The registry record specifies serial plasma concentration measurements, a 2-compartment modeling approach, and participant-level clearance values that were averaged. It also identifies a clinical rationale for examining dosing in this setting.

What the posted record does not establish is the numerical clearance observed in either group. It does not provide group means, standard deviations, confidence intervals, or a between-group estimate. Without those results, the size and precision of any difference cannot be evaluated. The record also does not report numerical findings for the listed secondary outcomes. The study’s stated purpose should not be confused with a reported demonstration of a particular clinical outcome.

The non-randomized design matters to interpretation. The two groups are based on kidney-function categories, not random allocation to competing dosing strategies. Even if group outcomes were available, a simple difference would not necessarily represent the causal effect of changing the dose. Differences in participant characteristics or care could contribute, and the registry record does not report an adjusted analysis addressing this issue.

The safety fields record zero serious adverse events, zero other adverse events, and zero deaths in each group, alongside the listed at-risk counts. Those data are limited to the entries and context reported in the registry record. They do not establish absence of risk or precise comparative safety.

In general, pharmacokinetic results can inform the development of dosing approaches, but a model-derived clearance measure is not the same as evidence of clinical benefit. The registry record does not report the model’s numerical estimates, the exact reduced dose, or results that would show how a dosing approach relates to clinical outcomes. Consequently, the record supports describing the study question and design, but not claiming that a specific dose is optimal or that a treatment succeeds or fails.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary endpoint is a model-derived pharmacokinetic quantity rather than a direct clinical outcome. Serial plasma TXA concentrations are used to estimate one clearance value per participant, and those values are then averaged. Interpretation therefore depends not only on the measurement schedule but also on how well the stated 2-compartment model represents the observed concentration profiles.

The groups are based on kidney function, which is directly relevant to the study’s stated dosing rationale. At the same time, the non-randomized design means the groups are not interchangeable by design. Any observed difference in clearance would need to be interpreted as an association unless the analysis and assumptions justified a stronger causal conclusion. The registry record does not report such an analysis.

The record also illustrates the difference between a study’s stated purpose and reported evidence. It describes the goal of developing dosing regimens, but it does not include numerical primary endpoint results or results for the listed secondary outcomes. A stated rationale and endpoint definition can identify an important research question, but cannot substitute for estimates and uncertainty.

Finally, the record lists sample-size assumptions for a planning illustration based on an observed effect, but does not report the numerical observed effect or the numerical planning results. Planning calculations are not observed power and do not replace an analysis of the collected data. For readers assessing statistical evidence, the absent group estimates, uncertainty measures, model diagnostics, and analysis details are central limitations.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most immediate limitation for interpreting results is that numerical outcomes are not reported in the registry record. This includes the primary group means and standard deviations for total body clearance, any between-group estimate, and uncertainty measures. Although secondary outcomes are listed, their numerical results are also not reported. The study question can be described, but the magnitude and precision of findings cannot be assessed.

The non-randomized allocation and kidney-function-based group definitions limit causal interpretation. The record does not report a statistical adjustment strategy or information on potential differences between groups beyond the kidney-function categories. It is therefore not possible to distinguish an effect attributable to dosing from differences associated with group membership.

The primary outcome relies on a 2-compartment model and curve-stripping to transform serial concentrations into one clearance estimate per participant. The registry record does not report fitted model parameters, model diagnostics, alternative model checks, or sensitivity analyses. It also does not state how incomplete concentration profiles were handled. These omissions restrict evaluation of the model-derived endpoint.

The exact reduced TXA dose for participants with kidney problems is not reported in the registry record. The record also does not specify the analysis population, missing-data methods, statistical tests, or multiplicity strategy. While the adverse-event fields list zero serious events, zero other events, and zero deaths in both groups, definitions and follow-up details are not reported. These limits prevent broad conclusions about either comparative safety or clinical outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Tranexamic Acid Dosing for Major Joint Replacement Surgery — NCT05075200.
• Registry record last updated 2025-12-09; status last verified 2025-02.
• Results first posted 2025-12-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed phase 2, parallel, non-randomized study of TXA dosing in hip and knee replacement surgery. Enrollment is listed as 21. Participants are described in two groups defined by kidney function: below 60 mL/min/1.73m2 or dialysis, and at least 60 mL/min/1.73m2. The primary endpoint is mean blood plasma TXA total body clearance in mL/min, derived from serial concentration measurements using a 2-compartment model.

The study description states that the hospital standard dose is 20mg/kg after anesthesia and that a lower dose is used for participants with kidney problems and lower kidney function; the reduced dose is not reported. The record lists secondary outcomes and adverse-event counts, but does not report numerical primary or secondary outcome results, analysis methods, missing-data handling, or an analysis population. The adverse-event fields list zero serious adverse events, zero other adverse events, and zero deaths in both groups.