This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (NCT03376061), a randomized phase 4 study. The primary outcome is Median Volume of Mediastinal Fluid Collected From Participants.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03376061 |
| Phase | Phase 4 |
| Condition | Bleeding, Surgical Blood Loss |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 97 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Population Health Research Institute |
| Results posted | Yes |
2. Clinical Question
Population
Patients undergoing cardiac surgery at Hamilton General Hospital were eligible for the study described in the registry summary. The record identifies bleeding and surgical blood loss as the conditions of interest; it does not report further eligibility details in the registry record.
Intervention
The topical arm received topical tranexamic acid or placebo. The description specifies a 50 mL syringe containing 5 g of tranexamic acid or placebo, applied in two equal portions to the pericardial mediastinal cavities during the operation.
Comparator
The comparator was intravenous tranexamic acid or placebo. The registry describes two 50 mL syringes for intravenous injection. The posted primary comparison is between the topical and intravenous arms.
Primary question
The primary outcome asks whether the median volume of fluid collected from mediastinal drainage tubes during the first 24 hours after surgery differs between the topical and intravenous groups. The posted summaries describe the observed distributions; a primary statistical comparison is not reported in the registry record.
The study is identified as a pilot whose stated aim was to assess the feasibility of conducting a larger international randomized trial. The registry summary also describes the research question as comparing topical application with usual intravenous tranexamic acid. The outcome and treatment descriptions establish what was compared, but they do not by themselves establish whether the groups differed beyond what could arise from sampling variation.
The registry does not report a formal primary-outcome hypothesis test, confidence interval, or adjusted estimate. The primary outcome is presented as a median and interquartile range for each arm. Those summaries allow readers to compare the observed central values and spread, but they do not replace an inferential analysis of the between-group contrast.
3. Trial Design
The registry identifies this as a completed, randomized, parallel-group Phase 4 study with quadruple masking. The record gives an enrollment of 97. Its summary describes a double-blinded, single-centre randomized controlled pilot trial at Hamilton General Hospital, while the design fields list quadruple masking. The record does not explain the difference between those masking descriptions, so the precise masking procedures are not reported in the registry record.
The two arms were topical tranexamic acid and intravenous tranexamic acid. The topical description specifies application to the pericardial mediastinal cavities during surgery. The intravenous description specifies injection. Each arm description also allows for placebo. The registry does not provide further details about how allocation was generated or concealed, or how the placebo procedures were implemented; these details are not reported in the registry record.
The study start date is 2017-12-21, and the primary completion date is 2018-09-04. The status is completed. The stated purpose was to assess feasibility for a larger international trial, rather than to establish a definitive treatment effect. The registry record does not report a protocol for progression from the pilot to a larger study, nor does it state whether a later trial was undertaken.
Results are posted for the primary drainage-volume outcome and for some secondary outcomes. No sponsor-reported analyses are listed in the registry record. This matters when reading the results: posted arm summaries are descriptive, and recalculated unadjusted comparisons for binary secondary outcomes are not a substitute for a prespecified analysis from the study team. The registry record does not report the analysis population, handling of missing observations, or a statistical analysis plan.
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
| Stage | Topical TxA (Intervention) | Intravenous TxA (Control) |
|---|---|---|
| STARTED | 49 | 48 |
| COMPLETED | 49 | 48 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Topical TxA (Intervention) | Intravenous TxA (Control) | Total |
|---|---|---|---|---|
| Participants analysed | 49 | 48 | 97 | |
| Age, Continuous | years | 67.3 (SD 9.4) | 67.8 (SD 9.2) | 67.5 (SD 9.2) |
| Sex: Female, Male: Female | Participants | 5 | 6 | 11 |
| Sex: Female, Male: Male | Participants | 44 | 42 | 86 |
| Race/Ethnicity, Customized: White/Caucasian | Participants | 46 | 46 | 92 |
| Race/Ethnicity, Customized: Hispanic/Latino | Participants | 0 | 2 | 2 |
| Race/Ethnicity, Customized: Southeast Asian/Malaysian | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Aboriginal/Native Persons | Participants | 2 | 0 | 2 |
| Region of Enrollment: Canada | participants | 49 | 48 | 97 |
| Diabetes mellitus | Participants | 17 | 21 | 38 |
| Stroke | Participants | 3 | 3 | 6 |
| Transient ischemic attack | Participants | 2 | 2 | 4 |
| Carotid endarterectomy/stent | Participants | 3 | 1 | 4 |
| History of seizures | Participants | 1 | 0 | 1 |
| New oral anticoagulants (NOAC) | Participants | 3 | 4 | 7 |
| Aspirin | Participants | 38 | 42 | 80 |
| Clopidogrel (Plavix) | Participants | 12 | 7 | 19 |
| Ticagrelor | Participants | 3 | 5 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Median Volume of Mediastinal Fluid Collected From Participants, measured over Fluid collected in the first 24 hours after the surgical procedure.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the median cumulative volume of fluid collected from mediastinal drainage tubes during the first 24 hours after the surgical procedure. It is measured in mL. The outcome is a direct measure of postoperative drainage during a defined period, and the registry identifies it as the primary measure of blood loss for this pilot comparison.
The posted median is 500 mL in the topical group, with an interquartile range of 350 to 750 mL. In the intravenous group, the median is 540 mL, with an interquartile range of 420 to 700 mL. The interquartile range describes the middle half of the observed values in each group; it communicates variability without assuming that the values are symmetrically distributed.
Using medians is a descriptive choice that can be useful when an outcome is skewed or contains unusually high values. That is a general statistical explanation, not a report of the distributional properties observed in this trial. The registry does not report a test of the primary endpoint, a confidence interval for the difference between medians, or an adjusted estimate. Therefore, the posted summaries describe the group distributions but do not establish the precision or statistical significance of a treatment contrast.
The endpoint is restricted to drainage collected during the first 24 hours. It does not, on its own, describe blood loss outside that period or capture every clinical consequence related to bleeding. The registry lists additional outcomes, including transfusion and re-operation, but those measures address different aspects of postoperative care.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The observed median drainage volume was 500 mL in the topical arm and 540 mL in the intravenous arm. The corresponding interquartile ranges were 350 to 750 mL and 420 to 700 mL. These are descriptive summaries. The registry record does not report a primary-outcome test or confidence interval, so the precision of the between-group contrast cannot be assessed from the posted primary result alone.
The interquartile ranges overlap. As a general statistical point, overlap or lack of overlap between separate interquartile ranges is not itself a formal test of a difference between groups. It also does not quantify uncertainty in the difference between medians. A formal analysis would need to estimate the contrast and its uncertainty using a method appropriate to the endpoint and study design; that analysis is not reported in the registry record.
The study is described as a pilot intended to assess feasibility for a larger trial. Its posted summaries therefore should not be treated as definitive evidence for or against a treatment effect. The registry does not report a primary inferential result, a sample-size justification for the trial, or a stated target effect for the primary endpoint. Those items are not reported in the registry record.
For the posted binary secondary outcomes, the comparison values are unadjusted recalculations from the arm-level counts. For seizures, the recalculated risk difference is -0.021, with a confidence interval from -0.061 to 0.020 and p = 0.31. For mortality, the recalculated risk difference is -< 0.001, with a confidence interval from -0.057 to 0.056 and p = 0.988. For RBC transfusion, the recalculated risk difference is -0.091, with a confidence interval from -0.288 to 0.105 and p = 0.364. These intervals include values on either side of no difference. They are wide, especially relative to the point estimates, and indicate limited precision in these comparisons.
These recalculated secondary comparisons are not reported sponsor analyses; the registry lists no reported analyses. They should be read as exploratory descriptions, not as a replacement for a prespecified analysis. The posted results do not establish that the treatments are equivalent, nor do they demonstrate a reliable difference. A non-significant p-value is not proof that there is no effect, and a point estimate alone does not show that an observed difference is precise or reproducible.
Deaths were recorded in each arm, while the adverse-event record lists zero participants affected by serious adverse events and zero affected by other adverse events in each arm. The record does not explain the relationship between the adverse-event categories and the mortality outcome. These figures should therefore be read as separate entries rather than combined into a causal or clinical conclusion.
9. Statistical Methods Explained
The registry reports arm-level summaries and does not list sponsor-reported analyses. Statistical explanations below are general where stated; they clarify how to read the posted statistics, but they do not describe an analysis plan that is absent from the registry record.
What do the median and interquartile range describe?
A median is the middle value after observations are ordered. It is less influenced by extreme values than a mean, which can make it useful for outcomes with an asymmetric distribution. The interquartile range gives the interval from the first quartile to the third quartile and describes the central spread of the observations. This is a general explanation of these statistics, not evidence that the trial outcome had any particular distributional shape.
For the primary drainage outcome, the posted medians and interquartile ranges are descriptive summaries for each arm. They do not directly estimate uncertainty in a contrast between arms. A comparison of medians would typically report an estimated difference and an interval or test that accounts for sampling uncertainty. No such primary comparison is reported in the registry record. The available summaries should not be used to create a new estimate of that contrast.
How should a risk difference be read?
A risk difference compares the observed proportions with an outcome in the intervention and control groups. A negative value in the posted comparisons indicates a lower observed proportion in the topical arm than in the intravenous arm, according to the direction used for those recalculations. The risk difference is an absolute measure: it expresses the difference between group proportions, rather than a relative ratio.
The confidence interval gives a range of values compatible with the data under the assumptions of the analysis. In general, wider intervals reflect less precision. If an interval includes zero for a risk difference, the data are compatible with no difference as well as with differences in either direction at the interval's stated confidence level. The registry does not identify a confidence level for these recalculated intervals, so no level should be inferred from the record.
The posted p-values for the binary comparisons are unadjusted. A p-value describes how unusual data at least as incompatible with a null hypothesis would be under that hypothesis and the assumptions of the test. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. The registry does not report a statistical analysis plan, including the test used for sponsor analyses; indeed, no sponsor analyses are listed.
What does “recalculated” mean for these comparisons?
The secondary risk differences, confidence intervals, and p-values are unadjusted recalculations from the posted arm summaries. They are not adjusted for baseline characteristics or other outcomes. No discrepancy is flagged in the record, but the recalculations remain distinct from a sponsor-reported analysis. If an inconsistency between a recalculation and the sponsor's own analysis were identified, the sponsor's analysis would take precedence; the registry record lists no sponsor analysis to compare against these results.
Arm-level counts are available for seizures, mortality, and RBC transfusion. The primary outcome is reported as medians and interquartile ranges. Other secondary outcomes are listed in the record, but the available results do not give a complete analysis for every listed outcome. The number of analyses reported in the registry is zero. The absence of a posted analysis means that details such as covariate adjustment, model choice, and prespecified contrasts are not reported in the registry record.
Why do over-dispersion and distributional assumptions matter?
General statistical context: a model that assumes the variability of count data follows a particular probability distribution can underestimate uncertainty when the observed variability is greater than that model allows. This is called over-dispersion. It can lead to intervals that are too narrow and p-values that are too small if it is ignored. This concern may be relevant in some count-outcome analyses, but the primary endpoint is reported as a median and interquartile range, and the registry does not report a model-based analysis or identify over-dispersion as an issue.
Likewise, a normal approximation is an assumption used in some planning calculations, not a guarantee about the distribution of observed data. The registry's planning illustrations specify a normal approximation and equal allocation. They are illustrations based on observed effects, not evidence that the trial was powered according to those calculations.
How should the planning illustrations be interpreted?
The posted planning calculations are explicitly based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. For mortality, the illustrations give participants per arm for 80% and 90% power at 100%, 75%, and 50% of the observed effect. For RBC transfusion, illustrations are given for the same effect fractions and power levels. For example, planning for 75% of the observed effect gives 3,125,643 participants per arm for 80% power and 4,184,348 participants per arm for 90% power for mortality; for RBC transfusion, the corresponding figures are 824 and 1,103.
These values are planning illustrations, not observed power and not the trial's enrollment target. They are sensitive to the small observed event counts and the estimated effect used as their starting point. The record does not report the trial's own sample-size justification, assumptions, or planned power, so those aspects are not reported in the registry record. A planning calculation based on an unstable pilot estimate should not be read as a reliable forecast of the size required for a definitive trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, but a plan for controlling multiplicity is not reported in the registry record. When several outcomes are tested, the chance of at least one apparently unusual result can increase. This is a general statistical concern; it does not establish that any particular posted result is spurious. The reported secondary p-values are unadjusted, and no correction or outcome hierarchy is reported.
The analysis population is not reported in the registry record. It is therefore unclear whether the posted results follow an intention-to-treat approach, a per-protocol approach, or another population definition. The registry does not explain whether participants were analyzed according to randomized assignment, whether any participants were excluded from particular outcomes, or how protocol deviations were handled.
Missing-data methods are also not reported in the registry record. The available arm summaries do not describe whether any outcome measurements were missing, how missingness was assessed, or whether imputation or other methods were used. Without that information, it is not possible to judge how missing observations may have affected the reported summaries or comparisons.
The registry does not report a statistical analysis plan, endpoint-specific modeling choices, covariate adjustments, or whether interim analyses were conducted. These items are not reported in the registry record; their absence should not be interpreted as evidence that a particular procedure was or was not used. No sponsor-reported analyses are listed. The recalculated unadjusted comparisons should consequently be treated as descriptive and exploratory rather than as a complete account of the trial's planned inferential analyses.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Topical TxA (Intervention) | 0 | 49 | 0.0% |
| Intravenous TxA (Control) | 0 | 48 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Topical TxA (Intervention) | 1 of 49 |
| Intravenous TxA (Control) | 1 of 48 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Topical TxA (Intervention) | 0 of 49 |
| Intravenous TxA (Control) | 0 of 48 |
The adverse-event record lists zero participants affected by serious adverse events in the topical arm and zero in the intravenous arm. It also lists zero participants affected by other adverse events in each arm. Separately, the mortality outcome records one death in each arm. These categories are reported separately in the registry, and their relationship is not explained.
The counts describe what is entered in the record; they do not establish that no other safety events occurred or that the treatments have equivalent safety. The registry does not provide event narratives, timing, causes of death, attribution to treatment, or details about ascertainment. Those details are not reported in the registry record.
With a pilot study and limited event counts, the absence of recorded affected participants in an adverse-event category cannot rule out uncommon events or precisely estimate risk. The mortality counts are also too sparse to support a confident comparison on their own. These figures should be read as descriptive safety information from this study, not as a comprehensive safety assessment or a causal conclusion about either treatment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this pilot compared topical and intravenous tranexamic acid in open cardiac surgery and posted arm-level summaries for mediastinal drainage during the first 24 hours. The primary summaries are medians and interquartile ranges. They provide a description of the observed outcome distributions in the two groups, but the record does not report a primary-outcome test or confidence interval for the between-group contrast.
The results do not show whether any apparent difference in the primary summaries is compatible with sampling variation, because the primary comparison's uncertainty is not reported. The available information therefore does not establish that one approach is better, worse, or equivalent. That interpretation is not a treatment recommendation; it is a limit on what can be concluded from the posted statistics.
The secondary comparisons are also limited. They are unadjusted recalculations from posted counts, have confidence intervals spanning no difference, and do not include a reported multiplicity adjustment. The sparse event information and absence of details about analysis populations or missing data further limit interpretation. Lack of a statistically significant result does not prove there is no difference, just as a point estimate does not by itself demonstrate a reliable treatment effect.
The stated purpose was to assess feasibility for a larger randomized trial. The record does not report feasibility outcomes beyond the stated aim, nor does it provide a trial-specific sample-size justification or a complete analysis plan. The planning illustrations based on observed secondary effects are not observed power and should not be mistaken for the study's original design calculation.
In short, the posted information is useful for understanding the study question, design, observed primary summaries, and selected secondary outcomes. It is not sufficient to provide a definitive estimate of the primary treatment contrast or a complete account of safety, missingness, or the planned analysis.
13. Why This Trial Matters Statistically
This trial illustrates a central statistical challenge in pilot studies: observed group summaries can describe what happened in the study, but small or exploratory studies may provide limited precision for treatment comparisons. The registry states that the study was intended to assess feasibility for a larger international trial. Its primary outcome is clinically relevant to the stated question, yet the record does not include an inferential comparison for that endpoint.
The distinction between descriptive and inferential results matters. Medians and interquartile ranges show the distributions' central values and spread in each arm; they do not quantify uncertainty in the difference between arms. Similarly, secondary risk differences and p-values recalculated from counts are exploratory and unadjusted, rather than sponsor-reported analyses. Clear labeling of these distinctions helps prevent overinterpretation.
The planning illustrations also demonstrate why pilot estimates require caution. Calculations based on observed effects can produce very different planning requirements depending on the assumed fraction of the observed effect. Such calculations are useful for illustrating sensitivity to assumptions, but they are not the original sample-size justification and do not represent observed power. The registry does not report the study's own sample-size rationale.
Finally, the record shows why completeness of reporting is part of statistical interpretation. The absence of a primary test, analysis population, missing-data approach, and multiplicity plan leaves important uncertainty about how results should be evaluated. These gaps do not negate the descriptive information, but they limit what can be concluded and underscore the value of prespecified, transparent reporting in later trials.
14. 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.
This trial-specific reading is limited by the information reported in the registry. The primary endpoint has arm-level medians and interquartile ranges, but no reported between-group estimate, confidence interval, or test. The primary result therefore cannot be evaluated for statistical precision from the registry record alone.
The registry describes the study as a pilot and states that its purpose was to assess feasibility. It does not report feasibility results in detail or a sample-size justification. The design fields identify quadruple masking, while the narrative describes a double-blinded trial; the record does not reconcile these descriptions. Allocation concealment and the specific masking procedures are not reported in the registry record.
Results are available for only some listed secondary outcomes in the information reported. The record does not provide results for re-operation for bleeding or tamponade, ICU hours, or plasma tranexamic acid concentration. Secondary comparisons are unadjusted recalculations, and no multiplicity strategy or analysis hierarchy is reported. Their confidence intervals are not a substitute for the missing primary comparison.
The analysis population, missing-data handling, protocol deviations, covariate adjustment, and interim analysis procedures are not reported in the registry record. Safety reporting is limited to affected-participant counts and deaths, without event descriptions, timing, or attribution. These reporting limitations restrict assessment of bias, precision, and the completeness of outcome ascertainment; they do not establish that any unreported procedure or event did or did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery — NCT03376061.
- Registry record last updated 2021-02-11; status last verified 2021-01.
- Results first posted 2019-09-09.
- 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.
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18. Record Summary
The registry record describes NCT03376061, a completed, randomized, parallel-group Phase 4 pilot study of topical versus intravenous tranexamic acid in open cardiac surgery. It reports quadruple masking in the design fields and describes a double-blinded, single-centre study in the narrative. Enrollment was 97. The study start date was 2017-12-21, and primary completion was 2018-09-04.
The primary outcome was median mediastinal drainage volume during the first 24 hours after surgery. Results are posted as arm-level medians and interquartile ranges, but a primary inferential comparison is not reported. Several secondary outcomes are listed; the available binary comparisons are unadjusted recalculations, and no sponsor-reported analyses are listed. The registry does not report a statistical analysis plan, missing-data approach, or multiplicity strategy.