Topical (Intra-Articular) Tranexamic Acid and Transfusion Rates Following Hip Hemiarthroplasty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical (Intra-Articular) Tranexamic Acid and Transfusion Rates Following Hip Hemiarthroplasty (NCT02664909), a randomized phase 4 study. The primary outcome is Number of Participants Who Needed Transfusions.

2. Clinical Question

This is a question about a binary outcome at the participant level: each participant either needed a transfusion during the stated period or did not. The registry describes the endpoint as the number of participants who needed transfusions and says that a rate would be calculated for each group. The comparison therefore concerns the frequency of participants with at least one transfusion, rather than the amount of blood transfused. Inpatient transfusion amount is listed separately as a secondary outcome.

The trial addresses a specific perioperative setting: topical application during hip hemiarthroplasty. Its result should be read as a comparison between the two assigned groups in this trial, not as a general estimate for other operations or patient populations. Further detail about eligibility, transfusion criteria, and the analysis population is not reported in the registry record.

3. Trial Design

The registry record describes a completed, randomized, parallel-group, Phase 4 trial sponsored by UConn Health. Enrollment was 36. The record lists quadruple masking, while the brief study summary calls the trial double-blinded and placebo-controlled. Both descriptions identify a placebo comparison, but the registry does not explain the difference in masking terminology or specify which roles were masked.

Participants were assigned to topical tranexamic acid or saline placebo during hip hemiarthroplasty. In the tranexamic acid group, 1 gram of drug was mixed with normal saline to a total volume of 50 cc and applied into the surgical wound at closure; half was delivered intra-articularly. In the placebo group, 50 cc of normal saline was applied at closure, half intra-articularly and half in the subfascial space. The procedure descriptions therefore indicate a difference in the contents of the application and also describe the placebo delivery locations.

The listed study start was 2016-01-01 and primary completion was 2019-06-30. The current status is completed. These dates describe the registry record and do not establish when results were analyzed or submitted. The registry record does not report the allocation ratio, method used to generate the random sequence, concealment procedures, or the identities of the masked roles. It also does not report a detailed protocol or statistical analysis plan.

Seventeen participants are listed in the tranexamic acid arm and 19 in the placebo arm for the primary outcome. Those arm counts sum to the stated enrollment, but the record does not describe participant flow, withdrawals, exclusions, or whether every enrolled participant was included in every outcome analysis. Randomization supports a comparison between assigned groups, but assessment of how that comparison was conducted requires the missing implementation and analysis details.

Six secondary outcomes are listed: inpatient transfusion amount; differences between pre- and post-operative hemoglobin and hematocrit; length of inpatient hospital stay; participants with post-operative complications; and inpatient hospitalization cost. Numerical results are detailed for length of stay and post-operative complications in the registry record. Numerical results for the other listed secondary outcomes 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 Number of Participants Who Needed Transfusions, measured over From the time of surgery until 2-4 days post-operative (length of inpatient hospital stay).

The primary endpoint is the number of participants who needed transfusions from the time of surgery until 2-4 days post-operative, corresponding to the length of the inpatient hospital stay in the endpoint description. The registry states that the rate of transfusion would be calculated for each study group. The reported counts are 0 of 17 participants assigned to tranexamic acid and 5 of 19 assigned to placebo.

This endpoint records whether a participant experienced the event, rather than how many transfusions an individual received or the quantity transfused. That distinction matters because a participant-level count gives each person one outcome classification for the primary comparison. Inpatient transfusion amount appears as a separate secondary outcome, so the primary result does not describe the volume of transfusion or the number of transfusion episodes.

In general, a transfusion endpoint is clinically relevant to a perioperative blood-management question because it captures an event occurring during the hospital stay. Its interpretation also depends on how transfusion need was defined and applied. Specific transfusion thresholds, decision rules, and adjudication procedures are not reported in the registry record. The endpoint’s observation period is limited to the period described in the record; it should not be read as capturing later transfusions beyond that period.

The result is a comparison of the observed event frequencies between the randomized groups. It does not, by itself, establish why the groups differed, nor does it provide information about all other outcomes that may matter after surgery. The other listed outcomes, including transfusion amount, hemoglobin and hematocrit changes, length of stay, complications, and hospitalization cost, address distinct questions.

7. Results Posted in the Registry

• Tranexamic Acid: 0.0% (0/17) versus 26.3% (5/19) on control; risk difference -26.3 percentage points (95% CI -46.1 to -6.5); unadjusted two-proportion z-test p = 0.023.

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.

Length of Inpatient Hospital Stay

• 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:
  • Tranexamic Acid: mean 3.90 versus 4.80 on control; difference -0.90 (95% CI -1.90 to 0.10), standardized effect d = -0.57; z-test p = 0.078.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tranexamic Acid and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Post-operative Complications

• 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: 35.3% (6/17) versus 57.9% (11/19) on control; risk difference -22.6 percentage points (95% CI -54.4 to 9.2), risk ratio 0.61 (0.29–1.29); unadjusted two-proportion z-test p = 0.175.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tranexamic Acid and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists six secondary outcomes, covering transfusion amount, changes in hemoglobin and hematocrit, length of inpatient stay, post-operative complications, and inpatient hospitalization cost. Numerical comparisons are detailed for length of stay and post-operative complications. Numerical results for the remaining listed outcomes are not reported in the registry record, so the full pattern across all six outcomes cannot be assessed from the posted numerical results.

The two outcomes with detailed comparisons have estimates in the same negative direction as the primary risk difference when expressed as tranexamic acid versus placebo. However, their confidence intervals include zero, and their unadjusted p-values are 0.078 and 0.175. They therefore provide less clear statistical evidence about a group difference than the primary outcome’s reported interval and p-value. Their uncertainty should be considered rather than treating the direction of their point estimates as confirmation of the primary result.

Secondary outcomes describe different aspects of the inpatient and post-operative course. They are not interchangeable with the primary transfusion endpoint: a difference in length of stay or complications would not directly establish a difference in transfusion need, and vice versa. The record does not report numerical results for several listed secondary outcomes, limiting the ability to judge whether the primary finding aligns with all other measured outcomes.

Unadjusted secondary comparisons carry less weight when several outcomes are examined because each additional test creates more opportunity for a nominally unusual result to occur by chance. This is a general statistical concern, not evidence that any particular result is false. The registry does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a prespecified strategy for interpreting them. Consequently, secondary p-values should be treated as exploratory signals rather than as a collection of independent confirmatory tests.

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

• Inpatient Transfusion Amount
• Difference Between Pre/Post-operative Hemoglobin
• Difference Between Pre/Post-operative Hematocrit
• Length of Inpatient Hospital Stay
• Number of Participants With Post-operative Complications
• Inpatient Hospitalization Cost

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either needed a transfusion during the stated inpatient period or did not. The registry reports the number with the event in each arm and a risk difference comparing tranexamic acid with placebo. A risk difference expresses the difference between the groups’ event proportions on an absolute scale. A value below zero for this contrast means the event proportion is lower in the tranexamic acid group than in the placebo group.

What does the confidence interval describe?

In general, a confidence interval gives a range of values that are compatible with the observed data under the statistical method used. It communicates uncertainty about the estimated group difference, rather than a range containing a known true value with certainty. For the primary risk difference, the reported interval extends from -0.461 to -0.065. Because the full interval is below zero, the interval does not include a null difference. The registry does not describe the interval-construction method or state its confidence level, so those details should not be inferred.

How should the p-value be read?

The primary unadjusted p-value is 0.023. In general, a p-value measures how unusual data at least as inconsistent with a specified null model would be if that model and the analysis assumptions were correct. It is not a probability that the treatment effect is absent, and it does not indicate the probability that the result will be reproduced. The registry does not describe whether the p-value came from a particular test or whether any covariate adjustment was used. The comparison is explicitly marked unadjusted.

Why does a small event count matter?

Only five transfusion events are reported in the placebo group, and none in the tranexamic acid group. With sparse binary outcomes, each participant’s outcome can have substantial influence on the group estimate. The absolute risk difference and its interval are useful for showing the scale and uncertainty of the comparison, but they cannot remove the limitations of having few events. General statistical methods for sparse outcomes can differ in their behavior; the specific method used for the registry comparison is not reported in the registry record.

What do the secondary analyses add?

Length of stay is a continuous outcome reported as a mean with a standard deviation in each arm. The comparison is a mean difference of -0.9 days, with an interval from -1.902 to 0.102 and an unadjusted p-value of 0.078. A mean difference compares group averages; the standard deviations describe variability among participants within each group. The interval includes zero, so the posted estimate is compatible with differences in either direction under that interval. The record does not report an adjusted analysis for this outcome.

Post-operative complications are reported as a participant count and compared using a risk difference. The estimated difference is -0.226, with an interval from -0.544 to 0.092 and an unadjusted p-value of 0.175. The interval includes zero. The registry also lists relative risk and odds ratio estimates for this outcome, but these are alternative measures of association and do not resolve the uncertainty shown by the interval. No analyses are reported for the other listed secondary outcomes in the detailed results.

What do the planning illustrations mean?

The record includes planning illustrations based on observed secondary-outcome effects. It states that these use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are planning examples, not the trial’s own sample-size justification and not observed power. The registry does not report the trial’s original sample-size assumptions or justification. The illustrations do not show that the trial had a particular probability of detecting an effect after the fact.

The planning values are shown as participants per arm for 80% power and participants per arm for 90% power, at the listed fractions of the observed effect. They should be interpreted as hypothetical design inputs derived from the observed results, not as additional trial findings. Because they depend on the observed effect, they do not independently validate the size or certainty of that effect.

The registry lists no reported analyses for the two secondary outcomes with detailed numerical comparisons. A reported analysis plan, model specification, missing-data approach, and analysis population are not reported in the registry record. Without those details, the posted estimates can be described and compared, but the full analytic process cannot be reconstructed from the record.

11. Confidence Intervals and Precision

The primary estimate is a risk difference of -0.263, with a reported confidence interval from -0.461 to -0.065. This interval is wholly below zero, indicating that the reported range of values does not include no difference. Its width also shows that the point estimate is not known with fine precision: values across a substantial range remain compatible with the data under the interval method. The registry record does not state the confidence level or the method used to construct the interval.

Precision needs to be considered with the event counts. The comparison includes 0 of 17 participants with transfusions in the tranexamic acid group and 5 of 19 in the placebo group. Those counts make the estimate dependent on a small number of observed events. An interval can express uncertainty, but it cannot compensate for limited information or establish that the same difference would be observed in another trial.

The secondary intervals are also informative about precision. The length-of-stay mean-difference interval runs from -1.902 to 0.102, and the post-operative-complications risk-difference interval runs from -0.544 to 0.092. Both include zero, and both allow values on either side of no difference. These results are less conclusive about the direction of their respective comparisons than the primary interval.

In general, a confidence interval should be read for both its position and its width. Whether it includes the null value is not a substitute for considering the range of plausible effect sizes, the outcome definition, and the amount of information in the data. The record does not give enough detail to assess interval construction, missing data, or the influence of any analysis choices.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and six secondary outcomes. It reports unadjusted comparisons for the primary endpoint and for the secondary outcomes with detailed numerical results, but does not report a multiplicity adjustment, a testing hierarchy, or a plan specifying which secondary comparisons were confirmatory. When several outcomes are tested, the chance of observing at least one nominally small p-value can increase. In general, adjustment or prespecified prioritization can help control that issue; whether either was used in this trial is not reported in the registry record.

The record lists 0 reported analyses, and the detailed secondary entries do not include reported analysis descriptions. A formal statistical analysis plan, covariate adjustment strategy, and model specifications are not reported in the registry record. The estimates can therefore be interpreted as the posted unadjusted comparisons, but the record does not provide enough information to reconstruct all analytic decisions or determine whether other planned analyses were conducted.

Missing-data handling is also not reported in the registry record. The listed primary arm counts are 17 and 19, but the record does not describe participant flow, missing outcome observations, exclusions, withdrawals, or imputation. It does not state whether all randomized participants were analyzed in the groups to which they were assigned. The analysis population is therefore not defined in the available record.

These omissions affect interpretation because analysis populations and missing-data assumptions can influence estimates, particularly in a small trial. They do not establish that data were missing or that exclusions occurred; they mean that these details cannot be assessed from the registry record. The record also does not describe interim analyses, stopping rules, or the original sample-size justification. No conclusions about those design features should be inferred from the posted results.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute kidney injury (5.9%), inpatient treatment for myocardial infarction (5.3%), demand ischemia (5.3%).

The registry reports serious adverse events affecting 1 of 17 participants in the tranexamic acid group and 2 of 19 in the placebo group. It also reports other adverse events affecting 6 of 17 and 11 of 19, respectively. No deaths are reported in either group. The record lists acute kidney injury at 5.9%, inpatient treatment for myocardial infarction at 5.3%, and demand ischemia at 5.3% among the top serious-event terms.

These figures are descriptive counts and listed terms, not a definitive comparison of safety between groups. The registry does not report whether events were considered related to treatment, how adverse events were collected or adjudicated, or whether participants could have experienced more than one event. The listed serious-event terms should not be interpreted as mutually exclusive participant groups or as evidence about causation.

The small arm counts limit how precisely differences in adverse events can be assessed. The absence of reported deaths in both groups does not establish the absence of other harms, and the registry record does not provide enough detail to assess event severity, timing, or completeness of reporting. These figures should be read as the adverse-event information posted for this trial, alongside the limits of its reporting.

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

The posted results show fewer participants needing a transfusion in the tranexamic acid group than in the placebo group during the stated inpatient period. The reported risk difference is -0.263, its confidence interval runs from -0.461 to -0.065, and the unadjusted p-value is 0.023. This is evidence of a difference in the observed groups under the reported comparison; it is not a guarantee that the same difference would occur in another study.

The result does not show how much blood was transfused, and it does not describe transfusions after the period from surgery until 2-4 days post-operative. Transfusion amount is a separate listed secondary outcome, for which numerical results are not reported in the registry record. The primary result also does not establish the effect on every other outcome, including length of stay, complications, laboratory changes, or hospitalization cost.

The trial enrolled 36 participants, and the primary outcome involved five reported transfusion events across the two groups. This limited amount of information affects how precisely the comparison can be estimated. The interval is important because it displays uncertainty around the point estimate; it does not remove uncertainty about reproducibility or applicability outside this particular trial.

The registry does not report the original sample-size justification, detailed analysis plan, handling of missing data, or analysis population. Those omissions limit assessment of the full design and analytic process. The result should therefore be interpreted as the posted randomized comparison, with attention to the small sample, sparse events, and incomplete reporting. It neither proves that an effect will be present in every setting nor establishes that there is no effect on outcomes not reported.

15. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should combine an effect estimate, its uncertainty, and the underlying event counts. The primary risk difference is negative and its reported interval lies below zero, while the observed counts are 0 of 17 versus 5 of 19. Seeing all three elements helps readers distinguish the direction of the observed comparison from the amount of information supporting it.

It also demonstrates the limits of relying on a p-value alone. The primary unadjusted p-value is 0.023, but that number does not convey the range of effect sizes compatible with the data or the impact of sparse events. The confidence interval and counts supply complementary information. The secondary comparisons further show why point estimates should not be read without their intervals: their estimates are negative, but their intervals include zero.

The record also makes reporting quality part of the statistical assessment. It identifies a randomized, parallel, masked, placebo-controlled design and posts arm-level results, but does not report the analysis population, missing-data methods, detailed analysis plan, or original sample-size justification. These details matter for judging how the estimates were produced and how well the posted analyses match the intended trial design.

Finally, the secondary outcomes raise a general multiplicity issue. Multiple outcomes can add useful context, but unadjusted comparisons do not carry the same confirmatory weight as a clearly prespecified primary analysis. The record does not describe how secondary outcomes were prioritized or adjusted. Reading the trial statistically therefore requires balancing a clear primary contrast against limited event information, incomplete analytic reporting, and secondary results that remain uncertain.

16. Limitations

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

The main trial-specific limitation is the small enrollment: 36 participants, with 17 in the tranexamic acid group and 19 in the placebo group. The primary endpoint has few observed events, which makes the estimate sensitive to a small number of participant outcomes. The reported interval communicates uncertainty, but the trial’s size restricts the amount of information available for the comparison.

The registry record gives limited detail about trial conduct and analysis. It does not report the randomization method, allocation concealment, masked roles, participant flow, analysis population, missing-data handling, or a detailed statistical analysis plan. Although the record describes quadruple masking and the brief summary calls the study double-blinded, it does not explain the difference. These gaps make it difficult to assess implementation and potential analytic choices.

The primary outcome is limited to the inpatient period described as surgery through 2-4 days post-operative. It does not, on its own, capture later transfusions. The registry does not report the transfusion threshold or decision process, and those details can matter when interpreting a clinical event that involves a treatment decision. The record also lists several secondary outcomes but does not provide numerical results for all of them.

Finally, the available adverse-event information is brief. It does not describe attribution, collection methods, event timing, or overlap among event categories. The trial’s findings are therefore best understood in the context of this specific surgical setting and the information posted, without assuming that all outcomes or design details are fully represented.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Topical (Intra-Articular) Tranexamic Acid and Transfusion Rates Following Hip Hemiarthroplasty — NCT02664909.
• Registry record last updated 2021-07-22; status last verified 2021-07.
• Results first posted 2021-07-21.
• 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.

20. Record Summary

The registry record identifies NCT02664909 as a completed Phase 4 randomized, parallel-group trial sponsored by UConn Health. It enrolled 36 participants undergoing hip hemiarthroplasty for femoral neck fractures and compared topical tranexamic acid with saline placebo. The listed start date is 2016-01-01, and primary completion is 2019-06-30.

The primary outcome was the number of participants needing transfusion during the inpatient period described as surgery through 2-4 days post-operative. The posted counts were 0 of 17 in the tranexamic acid group and 5 of 19 in the placebo group. The reported unadjusted risk difference was -0.263, with a confidence interval from -0.461 to -0.065 and an unadjusted p-value of 0.023.

The record lists six secondary outcomes and reports detailed numerical comparisons for length of stay and post-operative complications. It also posts adverse-event counts and serious-event terms. Details about the analysis plan, missing data, and analysis population are not reported in the registry record.