TXA in Spinal Fusion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for TXA in Spinal Fusion (NCT04272606), a randomized phase 2 study. The primary outcome is Transfusion.

2. Clinical Question

In statistical terms, the central question is whether the recorded transfusion experience differs between the randomized arms. That question requires outcome counts for each arm and a defined comparison that accounts for the outcome categories and their time windows. The record describes the endpoint but does not report the arm-level outcome counts, effect estimates, uncertainty intervals or test results needed to assess the comparison.

The trial also registered other topics of interest, including delirium severity, change in interleukin-6 concentration and length of postoperative stay prior to discharge. These outcomes do not replace the primary transfusion question. The record does not report their numerical results or the analysis procedures used for them.

3. Trial Design

This was a phase 2, randomized, parallel-group study with quadruple masking, according to the registry record. The official title describes it as prospective, randomized and double blind. The arm descriptions state 1:1 randomization. The treatment arm received tranexamic acid during surgery, while the comparison arm received standard of care treatment during surgery. Both arm descriptions include a visual acuity exam. Saline solution is listed among the interventions, and the summary refers to placebo.

The study concerned lumbar spinal fusion and instrumentation. The brief summary describes patients who elected to undergo lumbar interbody fusion on 2 or more levels. The registry lists degenerative disc disease as the condition. The enrollment field is 123. The record lists the study as completed, with a start date of 2020-08-01 and a primary completion date of 2023-06-12.

Random allocation is intended to make treatment assignment independent of participant characteristics, on average, although chance imbalances can remain. Masking is intended to reduce the influence of knowledge about assignment on care, assessment or reporting. The record labels masking as quadruple but does not specify which roles were masked or provide the procedures used to maintain masking. The official title’s description as double blind does not resolve that missing detail.

The record identifies six outcome measures and lists delirium severity, change in interleukin-6 concentration and length of postoperative stay prior to discharge as secondary outcomes. It describes a transfusion outcome with several categories and time points as primary. Details of the full outcome set, allocation concealment, participating sites, protocol deviations and analysis populations are not reported in the registry record. The registry lists no analyses. Consequently, the design features can be described, but the available record does not support a reconstruction of how the investigators analyzed the collected data.

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.

Before assignment: 37 subjects were excluded and not randomized due to the following reasons: * Exclusion criteria was found (14 subjects) * Surgery cancelled (8 subjects) * Subjects withdrew (5 subjects) * Surgery changed to min invasive and so subject did not qualify (3 subjects) * Surgeon decision (2 subjects) * trial on hold during randomization period (2 subjects) * study medication order problems (3 subjects)

Overall Study

Reasons for not completing this period:

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 Transfusion, measured over Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported.

The primary endpoint counts participants who had red blood cells transfused. Its description separates transfusions occurring intraoperatively, those occurring postoperatively before discharge or at day 5, and those occurring in either period. The stated assessment window is up to 5 days or until discharge, whichever came first; data were to be collected on the discharge day or day 5, as applicable.

This endpoint is used to capture whether participants received a transfusion during the specified perioperative period. As a participant-level outcome, each category can be interpreted as a count of people meeting that category’s definition, rather than as the total volume of blood transfused or the number of transfusion units. The registry does not define whether participants could appear in more than one of the separately described categories, nor does it report category-specific counts.

In general, a clearly specified endpoint helps connect the trial question to a measurable outcome. The timing rules matter because an outcome measured over different observation periods may not be comparable. Here, the stated stopping point is discharge or day 5, whichever occurred first. The record does not report additional rules for handling a transfusion after discharge, incomplete follow-up, or missing transfusion information.

The endpoint description alone does not show whether the treatment arms differed. Numerical counts by arm, a comparison estimate and a measure of uncertainty are not reported in the registry record. The three outcome categories also mean that a single, unambiguous primary comparison cannot be selected from the description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information available for this study is limited. The registry identifies randomization, a parallel-group model, quadruple masking and 1:1 assignment. It describes the primary outcome as participant counts in several transfusion categories. It does not report outcome analyses, so there are no posted primary effect estimates or inferential results to explain. General statistical concepts can clarify what those missing elements would ordinarily contribute, but they cannot fill in results that are not reported in the registry record.

What does randomization contribute?

In general, randomization assigns participants to study arms by chance according to a specified procedure. Its purpose is to reduce systematic differences in baseline characteristics between arms, so that a later outcome comparison is less confounded by the way participants were assigned. Randomization does not guarantee that every characteristic will be balanced in a particular trial. A comparison still depends on valid outcome measurement, appropriate handling of missing data and analysis consistent with the design. The registry states 1:1 randomization but does not describe the sequence-generation or allocation-concealment procedures.

What does masking contribute?

Masking can limit changes in treatment, assessment or reporting that arise when people know an assignment. The record labels masking quadruple, while the official title says double blind. It does not identify the roles covered by the quadruple label or explain how masking was maintained. This means the masking description can be reported, but the practical safeguards and the extent to which each role remained unaware of assignment are not reported in the registry record.

How should a participant count be analyzed?

For a defined outcome category, the number of participants with a transfusion is a count of participants meeting that category’s outcome definition. A statistical comparison would ordinarily also need the relevant number at risk or analyzed in each arm, along with an explicit choice of effect measure and method. For a binary outcome, analysts may compare event proportions or model the probability of the event; the appropriate method depends on the design and analysis plan. These are general descriptions, not methods attributed to this trial. The registry does not report its analysis method, the analyzed denominators for the primary endpoint, an effect measure or estimates.

The primary outcome description contains three related categories and time windows. In general, multiple outcome definitions require clarity about whether categories overlap, which comparison is primary, and how participants with incomplete observation are handled. A combined category can answer a different question from a category limited to events during surgery or after surgery. The record notes that the outcome has several categories or time points and was not reduced to one comparison. It does not report a hierarchy, a prespecified contrast or the analysis used for each category.

What would uncertainty measures show?

In general, an estimate without an uncertainty measure can give an incomplete picture. A confidence interval communicates the precision of an estimate and the range of values compatible with the data under the model and assumptions used. It does not establish that every value in the interval is equally plausible, and its interpretation depends on the analysis. A p-value addresses a different question: how the observed data compare with a null model. Statistical significance, by itself, does not describe the size or practical importance of an effect. No confidence intervals or p-values for the primary comparison are reported in the registry record.

What is the role of the planning illustration?

The registry describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. It says time-to-event illustrations give a total number of events using the Schoenfeld method, while other illustrations give participants per arm. These are planning assumptions, not evidence that the trial was originally designed using those assumptions, and not observed power. Numerical planning estimates are not reported in the record summarized by these registry entries. The registry does not report the trial’s own sample-size justification.

More generally, a planning calculation asks how much information a future study might need to detect a specified effect under stated assumptions. It does not establish the probability that a completed trial’s result is true, and it cannot substitute for an analysis of observed outcomes. A calculation based on an observed effect can be especially sensitive to how that effect was estimated. Since the record does not provide the primary outcome estimates or numerical planning results, no planning value or precision claim can be evaluated.

Why can over-dispersion matter?

As a general concept, over-dispersion occurs when variability in count data is greater than a model assumes. If an analysis treats counts as less variable than they are, standard errors may be too small and uncertainty may be understated. This concern is relevant to some count or rate models, but the registered primary outcome is described as the number of participants with a transfusion in defined categories. The record does not state that a count model was used, nor does it report evidence of over-dispersion or any adjustment for it. It would therefore be inappropriate to attribute a particular model or over-dispersion issue to this trial.

Overall, the registry supports a description of the design and endpoint but not a reconstruction of the statistical analysis. The analysis plan, model specifications, covariate adjustments, assumptions checks and inferential results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies six outcome measures and describes several primary transfusion categories, along with secondary outcomes including delirium severity, change in interleukin-6 concentration and length of postoperative stay prior to discharge. When a study examines multiple outcomes or multiple contrasts, the chance of at least one apparently unusual result can increase if each is tested separately without an appropriate plan. In general, a prespecified hierarchy or multiplicity adjustment can help clarify which results are confirmatory and how to interpret related tests.

The record does not report a multiplicity strategy, a hierarchy among the primary outcome categories, or a single primary contrast. It flags the primary outcome as having several categories or time points that were not reduced to one comparison. The registry lists 0 analyses. As a result, no multiplicity-adjusted or unadjusted outcome finding can be evaluated from the record.

Missing-data handling is also not reported in the registry record. The endpoint description sets the assessment window at up to 5 days or until discharge, whichever came first, but does not specify how missing transfusion status, early discharge, incomplete follow-up or other unavailable measurements were handled. The analysis population is not reported, and the record does not say whether participants were analyzed according to randomized assignment or another rule.

The record’s enrollment field is 123, while the adverse-event summaries list at-risk groups of 43 and 40. Those figures concern different reported fields; the record does not explain their relationship or identify the analysis population for the primary endpoint. No reconciliation should be inferred from the registry entries alone. The absence of an analysis plan or outcome analyses limits the assessment of missingness, multiplicity and population selection.

11. 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: pulmonary embolism (2.5%), embolic stroke (2.5%).

The registry lists serious and other adverse events separately. In the treatment arm, serious adverse events affected 0 of 43 participants at risk; other adverse events affected 6 of 43. In the placebo arm, serious adverse events affected 2 of 40 participants at risk; other adverse events affected 6 of 40. Deaths are listed as 0 in each arm. The record also lists pulmonary embolism and embolic stroke among the top serious terms, each at 2.5%.

These figures are descriptive counts as entered in the registry. They do not by themselves establish whether an event was caused by the assigned treatment, and the record does not report a formal statistical comparison, an uncertainty interval or detailed event-level timing. The serious-event terms are not linked to a specific arm in the information, so they should not be assigned to one.

In general, adverse-event summaries require attention to the definitions used, the observation period, the population at risk and whether events are counted by affected participants or event occurrences. The registry labels the figures as participants at risk and participants affected, but detailed definitions and analysis procedures are not reported in the registry record. Small or descriptive counts should not be treated as proof that a risk is absent or that two arms are equivalent.

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

The registry record establishes that a randomized phase 2 study compared tranexamic acid during surgery with a placebo or standard-care comparison for lumbar spinal fusion. It describes a primary transfusion outcome with intraoperative, postoperative and combined categories, assessed up to 5 days or discharge, whichever came first. It also lists several secondary outcomes and adverse-event summaries.

What the record does not establish is the comparative result for transfusion. Arm-level primary outcome counts, estimates of the difference, confidence intervals and p-values are not reported in the registry record. Without them, the direction, magnitude and precision of the primary comparison cannot be assessed. The registry’s completed status and its enrollment field do not fill that evidentiary gap.

The safety counts can be reported as recorded, but they do not constitute a full comparative safety analysis. They do not establish that an event was caused by treatment, and they do not show that a difference between arms is or is not statistically distinguishable. The serious-event terms listed in the record should be read as registry-reported terms, without assigning them to an arm where the record does not do so.

In general, a trial result is most informative when the outcome definition, analyzed population, effect estimate, uncertainty and analysis method can be considered together. A result that is not reported cannot be treated as a null finding. Nor can a planning illustration, which concerns assumptions for study planning, replace the observed outcome analysis.

The appropriate interpretation is therefore limited: the registry describes the question and design, and provides selected adverse-event counts, but it does not report the primary analysis needed to determine how the randomized arms compared on transfusion. No treatment-effect conclusion follows from the information reported in the registry record.

13. Why This Trial Matters Statistically

This study raises a useful statistical issue: a clearly named primary outcome can still require careful interpretation when its definition contains several categories and time points. Transfusion during surgery, transfusion after surgery and transfusion in either period are related but not identical questions. A reader needs to know how those categories relate, which comparison was planned as primary and how the analysis accounted for the specified observation window.

The randomized parallel-group design is also relevant to interpretation. Random allocation is intended to support a fair comparison, while masking can reduce some forms of assessment or treatment bias. But those design labels do not replace numerical outcome results. Estimation and uncertainty are needed to understand what the observed data say, and the registry record lists no analyses.

The record also illustrates why outcome reporting and analysis populations matter. The enrollment field is 123, while the safety summaries use at-risk counts of 43 and 40. The registry does not explain the relationship between these fields or provide primary-outcome denominators. Without that context, readers cannot trace how the enrolled group contributed to the reported summaries or evaluate missing outcome information.

Finally, the record lists multiple outcomes and several transfusion categories but does not report a multiplicity approach or outcome analysis. In general, prespecified outcome priorities and transparent reporting help readers distinguish planned comparisons from exploratory ones and interpret uncertainty appropriately. Here, the design and endpoint description are available, but the posted record does not provide the results required for those judgments.

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.

A central limitation of the available record is that it does not report numerical primary outcome results or any analyses. The primary endpoint is described through several transfusion categories, but counts by arm and comparative estimates are not reported. The record itself notes that the outcome has multiple categories or time points and was not reduced to one comparison. This prevents assessment of effect direction, size or precision.

Details needed to judge the analysis are also absent. The statistical analysis plan, handling of missing data, analysis populations, covariate adjustment, multiplicity strategy and outcome-specific denominators are not reported in the registry record. The record does not explain how the enrollment field of 123 relates to the safety summaries’ at-risk groups. No inference about exclusions, follow-up or participant flow should be made from that difference in reported fields.

The description of masking is incomplete: the registry labels it quadruple, while the official title says double blind, but the roles masked and procedures are not reported. The randomization method and allocation-concealment procedures are not reported either. The record gives limited detail on eligibility beyond degenerative disc disease and the summary’s description of patients electing multilevel lumbar interbody fusion. Further participant characteristics, site information and protocol details are not reported in the registry record.

The adverse-event figures are descriptive and lack a reported comparative analysis, uncertainty estimates and further event definitions. The record does not provide enough detail to attribute events to treatment or assess the completeness of safety follow-up. These limitations concern the information reported in the registry and do not establish that the trial itself lacked protocols, analyses or additional data.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: TXA in Spinal Fusion — NCT04272606.
• Registry record last updated 2024-12-12; status last verified 2024-11.
• Results first posted 2024-05-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes NCT04272606, titled TXA in Spinal Fusion, as a completed phase 2 randomized parallel-group study with quadruple masking. It compares tranexamic acid during surgery with a placebo or standard-care arm for lumbar spinal fusion and instrumentation. The record lists degenerative disc disease as the condition and an enrollment of 123.

The primary outcome is the number of participants receiving red blood cell transfusion intraoperatively, postoperatively before discharge or day 5, or in either period. The registry lists six outcome measures and secondary outcomes concerning delirium severity, interleukin-6 concentration and postoperative stay. It lists no analyses and does not report numerical primary outcome results or a statistical comparison.

Safety summaries report serious and other adverse events by arm, along with deaths and serious-event terms. These figures are descriptive; a formal comparative safety analysis is not reported in the registry record.