Multi-center Study to Evaluate the Safety of Apixaban (BMS-562247) in Indian Subjects Undergoing Elective Total Knee Replacement or Total Hip Replacement Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multi-center Study to Evaluate the Safety of Apixaban (BMS-562247) in Indian Subjects Undergoing Elective Total Knee Replacement or Total Hip Replacement Surgery (NCT01884337), a na phase 4 study. The primary outcome is Number of Participants With Composite of International Society on Thrombosis and Haemostasis (ISTH) Major Bleeding/Clinically Relevant Non-major Bleeding (CRNM) While Undergoing Elective TKR or THR at the End of Treatment + 2 Days.

2. Clinical Question

3. Trial Design

This is a phase IV, open-label, multi-center study of apixaban in Indian subjects undergoing elective total knee replacement or total hip replacement surgery. Its registered model is single-group, allocation is listed as NA, and masking is listed as none. The record therefore describes a safety study without a randomized control group. It explicitly cautions that the arms are not a like-for-like control comparison.

The intervention is apixaban 2.5 mg tablets taken by mouth twice daily. The recorded treatment duration is 12 days for TKR subjects and 35 days for THR subjects. The primary endpoint is assessed at the end of treatment plus 2 days, with separate timeframes of 2 weeks + 2 days for TKR and 5 weeks + 2 days for THR. These different follow-up windows should be kept in mind when interpreting the two surgery groups; the registry does not describe a direct comparative analysis between them.

Enrollment is recorded as 557. The serious and other adverse-event summaries separately list participants at risk in the TKR and THR groups. How these figures relate to enrollment, and how the participants were assigned to the event-summary groups, is not reported in the registry record. The record identifies the study as completed, with a start date of 2015-03-24 and a primary completion date of 2018-06-04.

The registry lists 2 outcome measures, including the primary bleeding endpoint and a secondary composite of VTE or all-cause death at the end of treatment plus 2 days. It lists 0 analyses. Details of the statistical plan, including any prespecified comparisons or adjustment methods, 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.

Before assignment: 557 participants were enrolled, of whom 498 were treated. Of the 59 who were not treated, 42 no longer met study criteria, 6 withdrew consent, 11 due to other reasons. Of the 326 who started Total Knee Replacement, 324 continued into follow-up period and of the 172 who started Total Hip Replacement, 170 continued into follow-up period.

Treatment

Reasons for not completing this period:

Follow-up Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug during the Treatment 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 Number of Participants With Composite of International Society on Thrombosis and Haemostasis (ISTH) Major Bleeding/Clinically Relevant Non-major Bleeding (CRNM) While Undergoing Elective TKR or THR at the End of Treatment + 2 Days, measured over 2 weeks + 2 days for TKR, 5 weeks + 2 days for THR.

The primary endpoint is a count of participants with either ISTH major bleeding or clinically relevant non-major bleeding (CRNM) during elective TKR or THR, assessed at the end of treatment plus 2 days. Its unit is participants, so the endpoint is intended to describe how many people met the composite bleeding definition, rather than the number of bleeding episodes or a rate per unit of follow-up.

The registry defines ISTH major bleeding using serious clinical criteria: fatal bleeding; bleeding in a critical organ or location; or bleeding associated with a fall in hemoglobin of 2 g/dL or more or transfusion of 2 units or more of packed red cells or whole blood within 24 hours. CRNM bleeding is described as clinically acute and overt bleeding that does not meet major-bleeding criteria but requires medical intervention. The example in the record refers to a visit to a physician's office, emergency room, or urgent care center for epistaxis. Any further CRNM definition beyond the text recorded is not reported in the registry record.

A composite endpoint can capture more than one clinically relevant type of event in a single measure. Its interpretation depends on the definitions and on which component events occurred. The registry does not report the primary endpoint count, a breakdown by bleeding component, or an analysis. Thus, the endpoint definition is available, but the result for this primary question is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study can describe the events observed in the participants who received the study intervention. Without a concurrent control group, it does not directly estimate how outcomes would have differed under another treatment or under no treatment. Observed events can be influenced by the participants’ health, the surgery, follow-up, and other circumstances, as well as by the intervention. The registry describes this study as single-group and explicitly says it is not a randomized comparison.

What does the primary count represent?

The primary outcome is a binary participant-level measure summarized as a count: each participant either meets the composite bleeding definition during the stated assessment period or does not. In general, a count is easiest to interpret alongside the population assessed and the definition of an event. The registry specifies that the endpoint population includes participants who received at least one dose during the Treatment Period. It does not report the observed primary count or the denominator used in an analysis, so a primary endpoint frequency cannot be read from this record.

The composite combines ISTH major bleeding and CRNM bleeding. In general, combining event types can make an endpoint capture a broader range of clinically important outcomes, but the overall result can be driven by one component more than another. Component-specific counts help clarify that interpretation. Such counts are not reported for the primary endpoint in the registry record.

How should uncertainty be assessed?

In general, a confidence interval describes a range of values compatible with the observed data under the statistical model used. It communicates precision as well as the estimate itself. A count without an analysis denominator or uncertainty interval does not show how precisely an underlying event frequency has been estimated. The registry lists 0 analyses and does not report a confidence interval for the primary endpoint or the adverse-event summaries.

For a study without a control group, uncertainty around an event frequency would not resolve the main causal limitation: the absence of a randomized treatment contrast. Even a precise description of observed events would remain a description of this study group rather than a randomized estimate of what would happen under an alternative intervention. No comparative effect estimate is reported in the registry record.

What do the planning assumptions mean?

The planning illustration associated with the posted material is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is based on a stated fraction of an observed effect. These are planning assumptions, not a description of the registered single-group design. The registry does not report a randomized two-arm comparison or the primary endpoint’s observed effect needed to interpret a specific illustration. Such sample-size illustrations are not observed power and should not be mistaken for a trial result or a protocol-based sample-size justification.

In general, a sample-size calculation asks what size of study would be needed under specified assumptions to detect a specified effect with a chosen probability and significance threshold. Its answer depends on the assumed effect and analysis model. It does not establish that the effect is real, nor does it show that the completed study had a particular probability of detecting an effect. The registry does not report the trial’s sample-size justification or statistical plan.

Why does the open-label design matter?

In general, when participants and investigators know the assigned intervention, expectations and clinical decisions can influence event recognition, reporting, and management. That possibility is especially relevant to outcomes that include clinical judgment, such as whether bleeding requires medical intervention. The registry specifies no masking, but does not describe independent event adjudication or other procedures that may have been used to standardize assessment. Those details are not reported in the registry record.

Why keep the surgery groups separate?

TKR and THR have different recorded treatment durations and endpoint timeframes. In general, counts collected over different observation periods may not be directly comparable as measures of risk. A comparison may require methods that account for follow-up duration and relevant group differences; the registry does not report such an analysis. The figures should therefore be read as descriptive summaries for the separately named surgery groups, not as evidence of a difference between them.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures: the primary composite of ISTH major bleeding or CRNM bleeding and a secondary composite of VTE or all-cause death. It lists 0 analyses. The statistical plan, including whether any endpoint was designated for confirmatory testing, is not reported in the registry record.

In general, when several outcomes are tested, the chance of at least one apparently notable result can increase if each is assessed separately without accounting for the number of tests. Methods for addressing this issue depend on the study’s goals and prespecified analysis plan. No multiplicity adjustment, testing hierarchy, or other approach is reported in the registry record. With no posted outcome analyses, there are no reported test results to interpret in relation to multiplicity.

The registry identifies the primary endpoint population as all participants who received at least one dose during the Treatment Period. It does not describe the analysis population used for the adverse-event summaries or explain how participants with missing assessments were handled. Reasons for missing data, the extent of missingness, and any imputation or sensitivity analyses are not reported in the registry record.

Enrollment is listed as 557, while the adverse-event summaries list separate at-risk groups for TKR and THR. The record does not explain the relationship between enrollment, the endpoint population, and these groups. This limits interpretation of the denominators and prevents a reader from inferring how participants without an event record or endpoint assessment were treated.

In general, missing outcome information can affect both the estimated event frequency and its precision, particularly when missingness is related to participants’ health or follow-up. Without information on missingness and analysis populations, the direction or extent of any such influence cannot be assessed from the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (0.3%), vertigo (0.3%), deep vein thrombosis (0.3%).

The serious adverse-event summaries are reported separately for the surgery groups. For TKR, the record lists 2 participants affected among 326 at risk; for THR, it lists 0 affected among 172 at risk. The record also lists other adverse events for 23 participants among 326 at risk in TKR and 6 among 172 at risk in THR. Deaths are recorded as 0 in each group. These are descriptive counts as posted, not estimates from a randomized comparison.

The record lists Anaemia, Vertigo, and Deep vein thrombosis among the top serious terms, each at 0.3%. These terms should not be confused with the primary composite bleeding endpoint: the registry does not provide a breakdown showing whether any particular serious event met the primary endpoint definition. Nor does it explain how the listed terms relate to the serious-event participant counts.

The at-risk figures are not the same as the recorded enrollment, and their relationship to enrollment is not reported in the registry record. The registry also does not report confidence intervals or an adjusted analysis for these summaries. A count of zero in a group means no deaths were recorded in that group in the posted summary; it does not establish that the underlying risk is zero. The different follow-up periods for TKR and THR also matter when reading the group summaries side by side.

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

The record documents a completed phase IV, open-label, single-group study of apixaban in Indian participants undergoing elective TKR or THR. It specifies the dose, the different treatment durations by surgery type, the primary bleeding endpoint, and selected adverse-event summaries. This information describes what the study was designed to assess and what event counts the registry posts.

It does not report the observed count for the primary composite of ISTH major bleeding or CRNM bleeding, a confidence interval for that endpoint, or an analysis of it. The secondary VTE or all-cause death composite also has no posted result in the record. Accordingly, the registry information does not establish the frequency or precision of either composite outcome.

The adverse-event counts are descriptive. Because there is no randomized control group, they cannot by themselves show what would have occurred with a different treatment or no apixaban. The TKR and THR groups are not described as randomized comparison arms, and the registry explicitly cautions that they are not like-for-like controls. Their event counts should not be interpreted as a causal comparison.

The figures also do not establish that a recorded event was caused by apixaban. In general, attributing an event to a treatment requires careful assessment of timing, alternative explanations, and an appropriate comparison; those analyses are not reported in the registry record. The open-label design and the registry’s lack of reported event-adjudication details further limit what can be inferred about event assessment.

Finally, the record does not explain why enrollment is 557 while the adverse-event summaries list 326 at risk for TKR and 172 at risk for THR. Without that reconciliation, readers should not infer how the populations relate. The safest interpretation is limited to the registered design and the specific posted counts, without extrapolating to unreported outcomes or comparative effects.

13. Why This Trial Matters Statistically

This study raises several important statistical issues for reading safety evidence. First, an observed event count is not a treatment effect. In a single-group study, counts can describe events among treated participants, but there is no randomized control group to help separate intervention-related events from events associated with surgery, underlying health, or other factors. That distinction is central when interpreting safety findings after major elective surgery.

Second, endpoint definitions matter. The primary measure combines ISTH major bleeding and CRNM bleeding, which have different criteria and levels of severity. The total count, if reported, would not by itself show which component contributed to the result. Component details would help explain what the composite captures, but are not reported for the primary endpoint in this record.

Third, denominators and follow-up need careful attention. The registry gives different treatment and endpoint timeframes for TKR and THR, and it lists separate at-risk counts for adverse events. It does not explain the relation between those counts and enrollment. Raw counts across groups with different observation periods and unclear analysis populations do not support a straightforward comparison.

Fourth, precision is essential to interpretation. Counts without confidence intervals or a described statistical analysis give limited information about how uncertain an underlying event frequency may be. The registry lists 0 analyses, so the primary endpoint’s statistical precision cannot be assessed from the record.

Finally, planning assumptions should be kept distinct from study results. A planning illustration based on a two-arm comparison does not change the registered single-group design and is not observed power. Together, these points show why a safety summary needs its endpoint definition, analysis population, follow-up, uncertainty, and design context to be read as a whole.

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 direct limitation for interpreting the primary question is that the registry describes the bleeding endpoint but does not report its observed participant count or a statistical analysis. The endpoint’s component-specific counts and uncertainty are also not reported in the registry record. As a result, readers cannot assess the primary bleeding frequency or its precision from the posted information.

The single-group, open-label design has no randomized control group. The registry expressly notes that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The TKR and THR summaries therefore cannot serve as a substitute for a randomized comparison. The record also does not report whether outcome assessment was independently adjudicated or otherwise standardized.

The record identifies enrollment as 557, but the adverse-event summaries list at-risk groups of 326 for TKR and 172 for THR. It does not explain this relationship or identify the analysis population for those summaries. Missing data, exclusions, follow-up completeness, and the handling of participants without endpoint assessments are not reported in the registry record.

TKR and THR have different treatment durations and endpoint timeframes. No method for accounting for those differences in any comparison is reported. The safety summaries do not include confidence intervals or adjusted analyses, and no statistical plan or sample-size justification is reported in the registry record. These omissions limit assessment of precision, comparability, and the basis for the study’s planned size.

The record lists no analyses, and it does not provide results for the primary or secondary composite outcomes. The available adverse-event counts should therefore be interpreted as the specific descriptive summaries recorded, not as a complete statistical evaluation of the trial’s safety objectives.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Multi-center Study to Evaluate the Safety of Apixaban (BMS-562247) in Indian Subjects Undergoing Elective Total Knee Replacement or Total Hip Replacement Surgery — NCT01884337.
• Registry record last updated 2019-11-29; status last verified 2019-11.
• 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.

18. Record Summary

NCT01884337 is a completed phase IV, open-label, multi-center, single-group study of apixaban in Indian subjects undergoing elective TKR or THR. The registered regimen is apixaban 2.5 mg by mouth twice daily, for 12 days for TKR subjects or 35 days for THR subjects. Enrollment is recorded as 557.

The primary endpoint is the participant count with ISTH major bleeding or CRNM bleeding at the end of treatment plus 2 days. The registry lists 2 outcome measures and 0 analyses. The primary endpoint result and secondary VTE or all-cause death result are not reported in the registry record.

Adverse-event summaries list serious events for 2 participants among 326 at risk in TKR and 0 among 172 at risk in THR; other adverse events are listed for 23 and 6 participants, respectively. Deaths are recorded as 0 in both groups. The registry does not explain how the adverse-event populations relate to enrollment. These descriptive figures do not constitute a randomized comparison or establish causation.