A Study of Tranexamic Acid (XP12B) in Women With Heavy Menstrual Bleeding: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Tranexamic Acid (XP12B) in Women With Heavy Menstrual Bleeding (NCT01280981), a non-randomized phase 3 study. The primary outcome is Participants With Treatment-Emergent Adverse Events (AEs).

2. Clinical Question

3. Trial Design

This was a Phase 3, multicenter, open-label extension study of tranexamic acid in women with menorrhagia. It enrolled people who had completed either of two pivotal efficacy studies, NCT00401193 or NCT00386308. Allocation was non-randomized, masking was absent, and the study used a single-group model. Consequently, there was no concurrent randomized control arm in this extension.

The planned treatment phase covered 9 menstrual periods. During menstruation, participants took tranexamic acid orally at a dose of 1.3 g three times daily for up to 5 days, with no more than 15 doses during a menstrual period. The registry describes a follow-up phone call approximately 30 days after the last dose, with a range of 25 to 35 days.

The study was completed. The registry lists enrollment of 288. The primary endpoint population is identified as the intent-to-treat population, while the adverse-event summary gives 260 participants at risk. The record does not explain how these populations relate or why their totals differ. Nor does it report the number who completed every treatment period or the follow-up call.

As an open-label extension, the study’s stated focus was safety during continued exposure, rather than a randomized estimate of comparative efficacy. The registry lists six outcome measures, including the primary treatment-emergent adverse-event outcome and secondary measures concerning gynecological examinations, blood pressure, laboratory values, intraocular pressure, and QTcFRI. A statistical analysis plan, interim-analysis details, and a sample-size justification 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat population (ITT)

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 Participants With Treatment-Emergent Adverse Events (AEs), measured over Day 1 to up to Month 9.

The primary endpoint counts participants with treatment-emergent adverse events from Day 1 to up to Month 9. The registry describes event groupings based on the investigator’s assessment of relationship to study drug; whether an event was serious or life-threatening; whether a participant died or withdrew because of an event; and whether a thrombotic or thromboembolic event occurred. The stated population is the intent-to-treat population.

Safety endpoints are used to describe adverse events observed during and after exposure, including their seriousness and clinical category. A participant count communicates how many people were recorded in a category, but it does not by itself show the timing, duration, severity, or causal relationship of every event. The event grouping and the investigator’s assessment are part of how these results should be read.

The registry’s primary endpoint is not an efficacy comparison. Because the extension has a single group and no randomized control, its adverse-event counts describe the participants receiving tranexamic acid in this study. They do not establish how those counts would compare with a control group. The record does not report a formal comparative analysis or a complete set of results for each primary-endpoint category.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study design determines what statistical conclusions are available. This extension had a single group, non-randomized allocation, and no masking. Statistical methods can describe the recorded events in that group, but without a concurrent randomized comparator they cannot produce a like-for-like randomized estimate of treatment differences. The registry does not report an alternative comparative analysis.

What does a participant count describe?

A participant count records the number of people meeting an outcome definition during the stated observation period. It is distinct from an event count: one participant may experience more than one event, while a person-level endpoint counts that participant according to the specified rule. The primary endpoint is described as a count of participants with treatment-emergent adverse events, grouped by event characteristics and investigator assessments. The registry does not provide detailed rules for deduplicating participants across categories in the posted summary.

The adverse-event summary reports 5 participants in the serious-event grouping and 218 in the other-event grouping, each among 260 at risk. These should be interpreted using their stated groupings, rather than as a comparison between treatment arms. The serious terms and their percentages are descriptive entries; the record does not explain the percentage denominator or fully specify whether these are participant proportions, event proportions, or another presentation convention. The reported percentages should therefore be read as listed, not used to reconstruct unreported counts.

Why does the design matter?

Random assignment, when used, helps make treatment groups comparable in expectation and supports estimation of differences between them. This study did not use random assignment and had no control group. Its single-group counts therefore describe what was recorded during tranexamic acid exposure, without a same-study counterfactual. Differences from an external population or another study would not substitute for a concurrent randomized comparison unless the relevant design and assumptions were established; those details are not reported in the registry record.

Open-label status means participants and investigators were not masked to treatment assignment. In general, knowledge of treatment can influence reporting, follow-up, and assessment, particularly for outcomes that depend on observation or judgment. This does not establish that a particular event assessment was biased, but it is a design feature to keep in mind when interpreting investigator-assessed event relationship and event descriptions.

What do uncertainty measures add?

In general, a confidence interval describes the range of estimates reasonably compatible with the data under a specified statistical model. It conveys sampling uncertainty that a point estimate alone does not. The registry summary does not list confidence intervals or other uncertainty estimates for the adverse-event counts. Consequently, it does not quantify how precisely the reported counts estimate a broader event frequency. Such estimates would also depend on the population and observation process to which the results are intended to apply.

In general, hypothesis tests assess data relative to a specified null hypothesis and analysis plan. A p-value is not the probability that a treatment works or that a result is due to chance. No outcome analyses are listed in the registry record, and no inferential result should be inferred from the descriptive counts. The analysis plan, test choices, and any adjustment for multiple outcomes are not reported in the registry record.

How should planning illustrations be understood?

In general, sample-size planning estimates how many participants a future study might need under specified assumptions about the target effect, variability, significance level, and desired power. Such a planning illustration is not an observed study result and is not observed power. The registry describes planning assumptions using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions do not match this single-group, non-randomized extension design. Any illustration based on them is a hypothetical two-arm planning exercise, not a retrospective measure of this study’s ability to detect an effect. The registry does not report that this was the trial’s own design justification.

For time-to-event outcomes, general methods may use event totals and assumptions about event rates and allocation; for other outcomes, planning commonly expresses a required number of participants per arm. No time-to-event primary endpoint or corresponding event total is described for this study. The registry does not provide the underlying observed effect or a planning result in the record summarized for these outcomes, so no such value can be interpreted as a finding from the trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and secondary outcomes concerning abnormal gynecological examinations, blood pressure at Week 36, treatment-emergent adverse experiences of laboratory values related to treatment, intraocular pressure at Month 9, and QTcFRI at Month 9. Considering multiple outcomes can raise a multiplicity issue: in general, the chance of at least one apparently unusual result can increase when many statistical tests are conducted. Whether and how to address that issue depends on the planned objectives and analysis strategy.

The statistical plan and any multiplicity adjustment are not reported in the registry record. The record lists 0 analyses, so readers should not infer that formal testing was conducted or that a particular adjustment was used. The outcomes can be described as registered measures, but no inferential conclusion across them can be recovered from their presence alone.

Missing-data methods are also not reported in the registry record. Enrollment was 288, the primary endpoint population is called intent to treat, and the safety summary reports 260 at risk. The record does not explain the difference, state how missing outcome data were handled, or report follow-up completeness by outcome. It is therefore not possible to determine from this summary whether counts reflect all enrolled participants, only participants with available observations, or a specific rule for incomplete follow-up.

The registry does not report details of interim analyses, imputation, sensitivity analyses, or reasons for missing observations. In general, missingness can affect interpretation when the probability of having an observed outcome is related to participant characteristics or events. Without information about missingness and its handling, the direction or size of any resulting influence cannot be assessed from the posted record.

11. Safety Results

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

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: menorrhagia (0.8%), blood glucose decreased (0.4%), carcinoid tumour of the stomach (0.4%), brain stem infarction (0.4%), intracranial aneurysm (0.4%).

The adverse-event summary reports 5 participants affected in the serious-event grouping, with 260 participants at risk. It separately reports 218 participants affected in the other-event grouping, also with 260 at risk. These are counts for the tranexamic acid group; they are not a comparison with a control group. The record does not provide a death count, so deaths are not reported in the registry record.

The listed serious-event terms are Menorrhagia, 0.8%; Blood glucose decreased, 0.4%; Carcinoid tumour of the stomach, 0.4%; Brain stem infarction, 0.4%; Intracranial aneurysm, 0.4%; and Trigeminal neuralgia, 0.4%. These percentages are quoted as recorded. The summary does not specify their denominator or explain whether a participant could appear under more than one term, so they should not be converted into participant counts.

In general, serious-event status and suspected relationship to study drug are separate classifications: seriousness describes an event category, while causality assessment concerns whether the event is considered related to treatment. The primary endpoint description says investigators assessed relationship to study drug, but the posted summary does not show those relationship counts. The observed counts alone do not establish that treatment caused or prevented an event.

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

The registry record describes a prolonged, open-label extension in which women who completed either of two pivotal efficacy studies received tranexamic acid during menstruation for up to 9 menstrual periods. Its primary focus was treatment-emergent adverse events over a period extending from Day 1 to up to Month 9. The posted safety data include participant counts in serious and other adverse-event groupings and a list of serious-event terms with percentages.

Those observations can help characterize events recorded in the study population during the extension. They do not by themselves establish the rate that would occur in a different population, provide a controlled estimate of risk, or determine whether an event was caused by study treatment. The non-randomized, single-group design has no concurrent control, and the open-label approach means treatment was not masked. These features limit causal and comparative interpretation.

The record does not provide a complete breakdown of all primary endpoint categories, the death count, uncertainty estimates, or outcome analyses. The difference between the enrollment total and the safety denominator is not explained. Missing-data procedures and the detailed statistical plan are also not reported in the registry record. These omissions limit assessment of the completeness and precision of the safety findings.

No conclusion about comparative efficacy follows from these safety counts. The record identifies secondary safety and measurement outcomes, but does not list analyses for them. The results are best understood as descriptive registry data from a single treatment group, rather than evidence of a treatment effect against a comparator or a definitive causal assessment.

13. Why This Trial Matters Statistically

Extension studies address a different statistical question from randomized efficacy trials. They can describe safety observations during continued treatment among participants who completed an earlier study, as this study did. That continuation context is relevant because it identifies the population being followed and the treatment exposure being observed. It also means the participants were selected through completion of one of the preceding pivotal studies, rather than drawn as a new, independent randomized sample.

The design makes the distinction between description and comparison especially important. A group-level count can tell readers what was recorded among participants at risk, but without a concurrent control it cannot estimate a randomized treatment contrast. The open-label design also makes assessment practices relevant when outcomes include investigator judgments about relationship to study drug or event classification.

The registry’s reporting illustrates why denominators and outcome definitions matter. Enrollment is 288, while the safety summary gives 260 at risk; the record does not explain this difference. The primary endpoint description includes several event categories, but the posted summary does not provide every category count or a death count. These are not minor presentation details: they affect what can be inferred about coverage, completeness, and the scope of the reported safety results.

Finally, the record distinguishes registered outcomes from statistical analyses. It lists a primary and secondary set of measures, but no analyses are listed. For clinical researchers, that distinction helps prevent descriptive counts from being mistaken for hypothesis tests or comparative evidence. The study is statistically informative as an example of safety follow-up, while its design and reporting constrain claims about precision and causality.

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 principal design limitation for interpretation is the absence of randomization, masking, and a concurrent control group. The study can describe events during treatment, but cannot provide a direct randomized comparison. The extension population was drawn from participants who completed either of two earlier efficacy studies; the registry does not report how that selection affects representativeness or generalizability.

The record reports 288 enrolled participants and an adverse-event denominator of 260 at risk, without explaining the difference. It does not report how many participants completed all 9 menstrual periods, reasons for discontinuation, or completeness of the follow-up phone call. Missing-data handling is not reported in the registry record, limiting evaluation of whether unobserved outcomes could affect the counts.

The posted primary endpoint summary does not include all category-specific results described in its definition. The death count is not reported in the registry record. Although the record lists serious-event terms and percentages, it does not clarify the percentage denominator or participant overlap across terms. The investigator’s relationship assessments are part of the endpoint definition, but their counts are not included in the posted summary.

Statistical analysis details, confidence intervals, hypothesis tests, interim analyses, and multiplicity procedures are not reported in the registry record. The registry also does not report the trial’s sample-size justification. These omissions mean the precision, analysis choices, and completeness of outcome reporting cannot be fully assessed from the record. The listed sample-size assumptions describe a two-arm planning illustration and should not be read as the design or achieved power of this single-group extension.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Tranexamic Acid (XP12B) in Women With Heavy Menstrual Bleeding — NCT01280981.
• Registry record last updated 2011-07-26; status last verified 2011-06.
• Results first posted 2011-07-26.
• 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

NCT01280981 was a completed Phase 3, multicenter, open-label extension study of oral tranexamic acid for women with menorrhagia who completed either of two pivotal efficacy studies. The single-group, non-randomized study enrolled 288 participants and planned treatment across 9 menstrual periods, with a follow-up phone call approximately 30 days after the last dose.

The primary endpoint counted participants with treatment-emergent adverse events from Day 1 to up to Month 9. The safety summary reports 5 participants in the serious-event grouping and 218 in the other-event grouping, each among 260 at risk. The record does not explain the difference between enrollment and the safety denominator, report a death count, or list outcome analyses. With no concurrent control group, these results are descriptive safety observations rather than a randomized comparative estimate.