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 The Effect on Blood Loss of Topical and Intravenous Tranexamic Acid in Cardiac Surgery Patients (NCT01895101), a randomized phase 4 study. The primary outcome is Postoperative Blood Loss.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01895101 |
| Phase | Phase 4 |
| Condition | Blood Loss, Tranexamic Acid, Cardiac Surgery |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 750 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Amphia Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Patients scheduled for cardiac surgery on cardiopulmonary bypass. The registry record describes the planned study groups but does not report further eligibility details or an analysis population definition.
Intervention
Pericardial lavage with 2 gr tranexamic acid diluted in 200 ml normothermic saline, given just before sternal closure. The registry record describes intravenous tranexamic acid as part of the anaesthetic protocol for all groups.
Comparator
Two comparison groups: pericardial lavage with 200 ml normothermic saline, or no pericardial lavage. Both groups also received the described intravenous regimen.
Primary question
Does adding topical tranexamic acid lavage reduce chest-tube blood loss 12 hours after cardiac surgery, compared with saline lavage or no lavage, when intravenous tranexamic acid is used in all groups?
The registry description states a hypothesis of a 25% reduction in postoperative blood loss with topical treatment added to intravenous treatment. That is the study's stated hypothesis, not a reported result. The primary outcome is reported as a median with an inter-quartile range for each arm. The registry record does not report a formal primary-outcome comparison, confidence interval, or p-value.
3. Trial Design
The registry record describes a randomized, quadruple-masked, parallel-group Phase 4 trial sponsored by Amphia Hospital. Its status is completed, and enrollment is listed as 750. The record lists a start of 2013-10 and primary completion of 2015-03. It describes three groups, with 250 participants planned in each: topical tranexamic acid lavage, saline lavage, and no lavage.
According to the arm descriptions, participants in all three groups received intravenous 2 gr tranexamic acid before sternal incision and 2 gr after cardiopulmonary bypass. The topical-treatment group also received pericardial lavage with 2 gr tranexamic acid in 200 ml normothermic saline. The saline group received pericardial lavage with 200 ml normothermic saline, and the third group received no pericardial lavage. The brief summary places lavage just before sternal closure.
The primary endpoint results list 249 participants for the saline-lavage group, 245 for the no-lavage group, and 245 for the tranexamic-acid-lavage group. These outcome denominators differ from the planned group counts. Reasons for the differences, the randomization method, allocation concealment, and the details of masking are not reported in the registry record.
The record names surgical re-exploration and cumulative red blood cell transfusions as secondary outcomes. It does not include posted analyses for the primary endpoint, and the secondary analysis list is empty. The registry record does not report protocol deviations or a participant flow account.
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 | Pericardial Lavage With 200 ml Normothermic Saline Solution | No Pericardial Lavage | 2 gr Tranexamic Acid Diluted in 200 ml Normothermic Saline |
|---|---|---|---|
| STARTED | 250 | 250 | 250 |
| COMPLETED | 249 | 245 | 245 |
| NOT COMPLETED | 1 | 5 | 5 |
Reasons for not completing this period:
| Reason | Pericardial Lavage With 200 ml Normothermic Saline Solution | No Pericardial Lavage | 2 gr Tranexamic Acid Diluted in 200 ml Normothermic Saline |
|---|---|---|---|
| OPCAB procedure | 1 | 1 | 3 |
| Withdrawal by Subject | 0 | 1 | 2 |
| another study, enrolled in other study | 0 | 1 | 0 |
| Death | 0 | 1 | 0 |
| coagulation disorder | 0 | 1 | 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 | Pericardial Lavage With 200 ml Normothermic Saline Solution | No Pericardial Lavage | 2 gr Tranexamic Acid Diluted in 200 ml Normothermic Saline | Total |
|---|---|---|---|---|---|
| Participants analysed | 249 | 245 | 245 | 739 | |
| Age, Continuous | years | 68 (62 to 75) | 68 (63 to 76) | 69 (62 to 75) | 69 (62 to 75) |
| Sex: Female, Male: Female | Participants | 45 | 65 | 49 | 159 |
| Sex: Female, Male: Male | Participants | 204 | 180 | 196 | 580 |
| Region of Enrollment: Netherlands | participants | 249 | 245 | 245 | 739 |
6. Primary Endpoint
The registry lists the primary outcome as Postoperative Blood Loss, measured over 12 hours postoperative.
| 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 postoperative blood loss in millilitres, measured as chest-tube production 12 hours after the surgical procedure. The registry describes this measurement as the main study parameter and specifies a median and inter-quartile range for its summary.
Chest-tube output is a direct measure of blood collected after surgery. It is used in this trial to assess postoperative bleeding during a defined period. The listed results are 290.0 ml, with an inter-quartile range of 210.0 to 410.0, for saline lavage; 300.0 ml, with an inter-quartile range of 190.0 to 450.0, for no lavage; and 290.0 ml, with an inter-quartile range of 190.0 to 430.0, for tranexamic-acid lavage. These summaries describe the observed distributions in the outcome groups; they do not by themselves establish whether differences between groups are statistically distinguishable.
General: a median identifies the middle of an ordered set of observations, while the inter-quartile range describes the middle half of those observations. An inter-quartile range is not a confidence interval and does not quantify uncertainty in a treatment comparison. The registry record does not report a primary endpoint confidence interval, p-value, or formal group-comparison result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint summaries are close across the three groups: the median is 290.0 ml with saline lavage, 300.0 ml with no lavage, and 290.0 ml with tranexamic-acid lavage. The inter-quartile ranges overlap substantially. These descriptive results do not show a large separation in the middle of the observed blood-loss distributions, but the registry record does not report a formal statistical comparison for this outcome.
The stated study hypothesis was that topical tranexamic acid would reduce 12-hour postoperative blood loss by 25% when added to intravenous treatment. The posted primary outcome summaries do not report an estimated treatment effect against that hypothesis, a confidence interval, or a p-value. It is therefore not possible from the registry results to quantify the precision of a treatment contrast or determine whether the stated reduction was supported. The medians alone cannot establish equivalence, absence of an effect, or a clinically important difference.
The outcome denominators are 249 for saline lavage, 245 for no lavage, and 245 for tranexamic-acid lavage. The planned allocation was 250 participants per group. The registry record does not explain the differences between planned group sizes and the outcome denominators, or state whether the displayed outcome groups reflect an intention-to-treat or another analysis population.
Secondary results include recalculated unadjusted comparisons for surgical re-exploration and red blood cell transfusions. Those estimates are not identified as sponsor-reported analyses, and the registry record lists no reported analyses. Their confidence intervals and unadjusted p-values should therefore be read as exploratory rather than as a complete prespecified analysis plan. In particular, multiple secondary comparisons can make isolated unadjusted results less persuasive.
For re-exploration, the recalculated risk-difference confidence intervals include zero for both comparisons with saline lavage. For transfusions, the recalculated confidence interval for the no-lavage comparison also includes zero; the topical-treatment comparison has an estimated mean difference of 0.0 and a confidence interval from -0.273 to 0.273. These intervals indicate substantial uncertainty in the secondary contrasts. They do not substitute for an unreported primary analysis, nor establish that groups are equivalent.
Overall, the registry record provides primary endpoint summaries but not the inferential results needed to answer its main statistical question. The posted numbers support a description of the observed outcomes, not a definitive claim about the effect of topical lavage.
9. Statistical Methods Explained
The registry record reports the primary blood-loss endpoint as a median and inter-quartile range. This is a descriptive approach that shows the center and spread of the observed outcome without requiring the mean to represent a possibly uneven distribution. The registry record does not report the statistical test, model, treatment contrast, or uncertainty interval used for the primary endpoint. Accordingly, the displayed medians and ranges should not be treated as a formal test of the trial hypothesis.
How should the primary summaries be read?
The median blood loss is 290.0 ml in the saline-lavage group, 300.0 ml in the no-lavage group, and 290.0 ml in the tranexamic-acid-lavage group. The respective inter-quartile ranges are 210.0 to 410.0, 190.0 to 450.0, and 190.0 to 430.0. General: the inter-quartile range is a description of observed spread, not a measure of uncertainty around the median or of uncertainty in a between-group effect. Overlapping inter-quartile ranges do not constitute a statistical test.
What do the secondary confidence intervals mean?
The comparison estimates listed for secondary outcomes are recalculated unadjusted estimates from the posted summary statistics. For surgical re-exploration, the risk difference is -0.003 for no lavage compared with saline lavage, with a 95% confidence interval from -0.037 to 0.030 and an unadjusted p-value of 0.843. For tranexamic-acid lavage compared with saline lavage, the risk difference is 0.009, with a 95% confidence interval from -0.028 to 0.045 and an unadjusted p-value of 0.635.
For red blood cell transfusions, the recalculated mean difference is 0.4 for no lavage compared with saline lavage, with a 95% confidence interval from -0.047 to 0.847 and an unadjusted p-value of 0.08. The mean difference for tranexamic-acid lavage compared with saline lavage is 0.0, with a 95% confidence interval from -0.273 to 0.273 and an unadjusted p-value of 1.0. General: a confidence interval gives a range of values compatible with the data under the assumptions of the method. When an interval includes zero for a difference, the data do not clearly distinguish that difference from no difference at the stated confidence level. An interval that includes zero does not prove equality.
Why are the secondary calculations unadjusted?
The p-values are unadjusted, meaning that they do not account for the several comparisons and outcomes in the registry record. General: when many hypotheses are tested, the chance of at least one apparently notable result can increase. A multiplicity adjustment or a prespecified hierarchy can address that issue, but such a plan is not reported in the registry record. The secondary p-values should therefore not be treated as confirmatory on their own.
How should the planning illustrations be interpreted?
The planning illustrations use the observed effect as their starting point and assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is a stated fraction of the observed effect. For example, planning for 75% of the observed effect is an illustration based on that assumed effect size, not an observed trial result. The record explicitly characterizes these calculations as planning illustrations rather than the trial's own design. They are not observed power and do not show the probability that the completed study detected an effect. The registry record does not report its own sample-size justification.
Some planning illustrations are listed for the re-exploration contrasts and for the transfusion comparison between no lavage and saline lavage. A corresponding illustration is not listed for the transfusion comparison between tranexamic-acid lavage and saline lavage. The recalculated effect for that comparison is 0.0, so an observed-effect-based illustration is not presented in the registry material.
What analysis details remain unknown?
The registry record lists zero reported analyses for the primary outcome and no reported analyses for the secondary outcomes. It does not report the primary-outcome test or model, covariate adjustment, handling of missing outcome data, analysis population, or multiplicity procedure. The posted secondary comparisons are explicitly recalculated, unadjusted summaries and should be distinguished from a sponsor's prespecified analysis. General: confidence intervals and p-values depend on the chosen model and its assumptions; without a reported analysis plan, the recalculated estimates cannot establish which method the trial investigators intended to use.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists no reported primary or secondary analyses. It does not report whether the trial had a prespecified multiplicity strategy, a hierarchy of endpoints, or adjustments for the two secondary outcomes and their multiple group comparisons. The posted secondary p-values are unadjusted recalculations. They should not be interpreted as if a family-wise error strategy or a confirmatory testing sequence had been applied.
The record also does not report how missing data were handled, whether any participants were excluded from outcome analyses, or the analysis population definition. The primary outcome denominators are 249, 245, and 245, while the planned group allocation was 250 per group. Those figures indicate that the outcome summaries do not use all of the planned participants in each group, but the reason is not reported in the registry record. No imputation approach, sensitivity analysis, or missingness pattern is described.
Randomization is listed, but the registry record does not describe the method used to generate the allocation sequence or conceal it. Quadruple masking is listed without specifying which roles were masked or how masking was maintained. The record does not report interim analyses, stopping boundaries, or a monitoring procedure. It also does not provide a primary-outcome analysis model or an account of protocol deviations.
General: missing-data handling matters because an analysis restricted to observed outcomes can be misleading if outcome availability is related to the outcome or assigned group. Multiplicity matters because several tests can increase the chance of an apparently unusual result. Without these details, the recalculated secondary estimates remain useful descriptions of the posted summaries but have limited confirmatory interpretation.
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 |
|---|---|---|---|
| Pericardial Lavage With 200 ml Normothermic Saline Solution | 7 | 250 | 2.8% |
| No Pericardial Lavage | 4 | 250 | 1.6% |
| 2 gr Tranexamic Acid Diluted in 200 ml Normothermic Saline | 4 | 250 | 1.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pericardial Lavage With 200 ml Normothermic Saline Solution | 0 of 250 |
| No Pericardial Lavage | 0 of 250 |
| 2 gr Tranexamic Acid Diluted in 200 ml Normothermic Saline | 0 of 250 |
Most frequent serious adverse event terms
| Event term | Organ system | Pericardial Lavage With 200 ml Normothermic Saline Solution | No Pericardial Lavage | 2 gr Tranexamic Acid Diluted in 200 ml Normothermic Saline |
|---|---|---|---|---|
| Death | Cardiac disorders | 4 of 250 | 2 of 250 | 2 of 250 |
| cerebrovascular accident | General disorders | 3 of 250 | 1 of 250 | 2 of 250 |
| epileptic seizures | General disorders | 0 of 250 | 1 of 250 | 0 of 250 |
Serious events with the highest arm-level rate: death (1.6%), cerebrovascular accident (1.2%), epileptic seizures (0.4%).
The registry record lists serious adverse events for 250 participants at risk in each group. The affected counts are 7 for saline lavage, 4 for no lavage, and 4 for tranexamic-acid lavage. It lists 0 other adverse events in each group. Arm-specific death counts are not reported in the registry record.
The serious-event terms listed across the record include Death at 1.6%, cerebrovascular accident at 1.2%, and epileptic seizures at 0.4%. The registry record does not provide arm-specific counts for these terms, so they should not be attributed to a particular treatment group. It also does not state whether each affected participant experienced one or more events, or give event timing, severity details beyond the serious classification, or causal attribution.
General: serious adverse-event counts describe events recorded under the registry's reporting definitions; they do not by themselves establish that an intervention caused an event. Small differences in counts should be interpreted cautiously without the full safety analysis, follow-up details, and group-specific event information. No arm-specific death count can be inferred from the aggregate serious-event terms.
12. What the Result Does, and Does Not, Mean
The posted primary outcome summaries describe blood loss at 12 hours after surgery in the three randomized groups. The medians are 290.0 ml for saline lavage, 300.0 ml for no lavage, and 290.0 ml for tranexamic-acid lavage, with broad and overlapping inter-quartile ranges. This is a descriptive pattern, not a formal estimate of the added effect of topical tranexamic acid.
The trial's stated hypothesis concerned a 25% reduction in postoperative blood loss when topical tranexamic acid was added to intravenous treatment. The registry record does not report a primary comparison, confidence interval, p-value, or analysis method. The posted information therefore does not quantify how compatible the data are with that target or with other possible treatment effects. Similar medians do not prove that the groups are equivalent, and the absence of a reported test is not evidence that no effect exists.
The secondary outcomes add information about re-exploration and transfusions, but the available comparisons are unadjusted recalculations. Their uncertainty and the absence of a reported multiplicity plan limit the strength of conclusions that can be drawn from them. Likewise, the serious-event counts are descriptive, with no arm-specific breakdown for the listed serious terms.
General: statistical uncertainty is not the same as absence of an effect. A precise estimate can rule out some values more effectively than an imprecise estimate; the registry record does not provide a primary-outcome interval that would permit that assessment. The posted summaries can characterize the trial's reported outcomes, but they cannot establish the success or failure of the stated hypothesis or support a causal conclusion beyond the information reported.
13. Why This Trial Matters Statistically
This trial is statistically notable for separating a clinically specific question from a shared background treatment. All three groups are described as receiving intravenous tranexamic acid, while the randomized contrast concerns topical lavage with tranexamic acid, saline lavage, or no lavage. The design therefore concerns the added contribution of the topical procedure within the stated treatment context, rather than a comparison of intravenous tranexamic acid with no intravenous treatment.
The registry record illustrates why the endpoint's summary and its inferential analysis are distinct. Medians and inter-quartile ranges describe the observed distributions, but they do not provide a confidence interval or hypothesis test for the between-group effect. Although the registry states a 25% reduction hypothesis, the primary result is not accompanied by an estimated contrast or uncertainty interval. That reporting gap limits assessment of precision and of the relationship between the observed data and the stated target.
The secondary outcomes also demonstrate the importance of distinguishing recalculated, unadjusted comparisons from reported trial analyses. Their estimates can help describe the posted summaries, but the absence of reported analyses and a multiplicity plan means they should not be treated as a complete confirmatory analysis. Planning illustrations based on observed effects are similarly different from the original sample-size rationale and from observed power.
For clinical researchers, the record is a reminder that randomization and masking labels alone do not convey the full statistical design. Understanding an estimate requires the analysis population, missing-data approach, model, and prespecified testing strategy. Those details are not reported in the registry record, leaving important limits on how strongly the results can be interpreted.
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.
The most important limitation for interpreting this registry record is the lack of a reported primary-outcome comparison. The primary endpoint is summarized by arm, but no treatment contrast, confidence interval, p-value, test, or model is reported. This prevents a direct assessment of the stated 25% reduction hypothesis and of the precision of the between-group effect.
Outcome denominators are lower than the planned 250 per arm, and the registry record does not explain why. It does not report participant flow, reasons for missing outcomes, analysis population definitions, or missing-data handling. These omissions make it difficult to assess whether the available outcome summaries represent all randomized participants or whether exclusions could have affected the results.
The record lists a randomized, quadruple-masked design but does not describe the randomization procedure, allocation concealment, or the roles covered by masking. It also does not report protocol deviations, interim analyses, stopping procedures, or the trial's own sample-size justification. These details are not available for judging implementation or the prespecified statistical approach.
The secondary comparisons are recalculated and unadjusted, and the record lists no reported analyses. No multiplicity strategy is reported. The safety information includes group-level serious-event counts but not arm-specific counts for the serious terms, including Death. Finally, the registry description says the groups were planned at 250 each, while posted outcome summaries use different denominators; the record does not explain that discrepancy. These limitations concern the information available in the registry record and do not establish what may be described elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effect on Blood Loss of Topical and Intravenous Tranexamic Acid in Cardiac Surgery Patients — NCT01895101.
- Registry record last updated 2015-05-20; status last verified 2015-05.
- Results first posted 2015-04-10.
- 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
NCT01895101 is a completed randomized, quadruple-masked, parallel-group Phase 4 trial sponsored by Amphia Hospital, with enrollment listed as 750. It compared pericardial tranexamic-acid lavage, saline lavage, and no lavage in cardiac surgery patients; the arm descriptions specify intravenous tranexamic acid for all groups.
The primary endpoint was chest-tube blood loss 12 hours after surgery, reported as a median and inter-quartile range. The record also lists surgical re-exploration and cumulative red blood cell transfusions as secondary outcomes and reports serious adverse-event counts.
The registry record does not report a formal primary-outcome analysis, a sample-size justification, missing-data methods, or multiplicity handling. Secondary comparisons are recalculated and unadjusted, while the record lists no reported analyses.