Can Rivaroxaban Lead to Anticoagulation-Related Nephropathy?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Can Rivaroxaban Lead to Anticoagulation-Related Nephropathy? (NCT02900170), a registered phase not stated study. The primary outcome is Incidence of Anticoagulant-related Nephropathy in the Cohort.

2. Clinical Question

3. Trial Design

The registry record describes a completed cohort study named Can Rivaroxaban Lead to Anticoagulation-Related Nephropathy? Its stated subject is the incidence of anticoagulant-related nephropathy in participants taking rivaroxaban. Enrollment is reported as 8. The listed condition is acute kidney injury, and the primary endpoint is an incidence measure expressed as a percentage of participants.

The endpoint is assessed over 6 months. Anticoagulant-related nephropathy is not defined by a creatinine change alone: the record also requires that a standard clinical evaluation and work-up by the participant’s primary care physician, cardiologist, or nephrologist find no other obvious cause of the acute kidney injury. This makes clinical assessment part of the outcome definition.

The record does not state an allocation method or identify a comparator arm. It therefore does not document randomization or a controlled treatment comparison. Details such as the recruitment approach, eligibility criteria, treatment regimen, visit schedule, frequency of creatinine measurement, and follow-up completeness are not reported in the registry record.

The study status is COMPLETED, and the primary completion date is 2018-06-11. Completion status describes the study’s administrative status; it does not itself establish that the primary outcome was analyzed or reported. Although the record lists a primary endpoint, it does not include an endpoint analysis. The registry record also does not describe the protocol’s sample-size justification, interim analyses, or a statistical analysis plan.

Planning illustrations use assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe a hypothetical planning exercise, not the documented cohort design. They should not be read as evidence that the study randomized participants or enrolled a comparison arm.

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:

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 Incidence of Anticoagulant-related Nephropathy in the Cohort, measured over 6 months.

The primary endpoint is the incidence of anticoagulant-related nephropathy in the cohort, expressed as a percentage of participants over 6 months. The endpoint identifies acute kidney injury through an increase in baseline serum creatinine of at least 0.3 mg/dL. It further requires that a standard clinical evaluation and work-up identify no other obvious cause for the injury.

This definition is intended to distinguish a kidney injury temporally observed in the setting of anticoagulant exposure from an injury with another apparent explanation. The requirement for clinical evaluation is important because a creatinine rise is a measurement, not by itself a diagnosis of anticoagulant-related nephropathy. Attribution depends on assessing possible alternative causes.

As a percentage, incidence is intended to communicate the proportion of the cohort meeting the outcome definition during the stated follow-up period. Its interpretation depends on consistent outcome ascertainment, complete follow-up, and a clear denominator. The registry record does not report how often creatinine was measured, how missing follow-up was handled, or how endpoint assessments were reviewed.

The endpoint is specified in the registry record, but its observed value is not reported in the registry record. The adverse-event counts do not substitute for this endpoint: acute kidney injury meeting the primary definition and serious adverse events are distinct outcome concepts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint such as whether a participant meets a defined acute kidney injury criterion, an incidence percentage is a simple summary of how frequently the outcome is observed in the cohort. The interpretation depends on both the event count and the number of participants whose outcome status can be assessed. The registry record reports enrollment of 8, but does not report a primary endpoint count, an analyzed denominator, or an incidence estimate. The percentage therefore cannot be reconstructed from the record.

What does a confidence interval convey?

In general, a confidence interval describes statistical uncertainty around an estimate under a specified method and its assumptions. A narrow interval indicates greater precision than a wide interval, while neither interval removes possible bias from outcome misclassification, incomplete follow-up, or selection into the cohort. For an incidence estimate, uncertainty is especially important when the cohort is small or events are sparse. No primary outcome confidence interval is reported in the registry record, so its precision cannot be evaluated.

Why can sparse events be difficult to analyze?

In general, methods that rely on large-sample approximations may perform poorly when event counts are low. Estimates can be unstable, and interval methods can have limitations near the boundaries of possible percentages. Exact or otherwise suitable methods may be considered depending on the analysis question, but the registry record does not identify a method for estimating the primary endpoint or its uncertainty. No method should be attributed to the study without that documentation.

Why does outcome definition matter?

The primary endpoint combines a laboratory criterion with clinical judgment. The creatinine increase must reach at least 0.3 mg/dL, and a standard clinical work-up must find no other obvious cause. This is more specific than counting any creatinine increase, but the result still depends on the timing and availability of measurements and on how potential causes are assessed. The registry record does not describe measurement schedules, adjudication procedures, or consistency checks. Without those details, the reproducibility of endpoint classification cannot be assessed.

What can a cohort estimate?

In general, a cohort can describe the occurrence of an outcome among the participants followed under the recorded conditions. A comparison between exposure groups requires clearly defined groups and an appropriate analysis; causal interpretation also depends on how differences between groups are addressed. The record identifies no comparator and does not state allocation. It therefore describes an incidence question, not a documented randomized comparison. Potential confounding and selection effects cannot be evaluated from the registry information available.

How should planning calculations be read?

The planning assumptions state a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe planning illustrations based on a fraction of the observed effect. Such calculations ask how many participants per arm might be needed under their assumptions; they are not results from the cohort and are never observed power. In particular, hypothetical equal allocation between two arms does not establish that this cohort had arms. The registry record does not report the protocol’s own sample-size justification, and it does not report a primary effect estimate from which the observed-effect basis could be assessed.

General caution applies when planning uses an effect estimated from a small study: the estimate may be unstable, and planning results can depend strongly on the selected effect and model assumptions. A planning illustration does not show that a study has adequate precision, and it cannot recover an unreported endpoint result. No numerical planning estimates are stated in the registry record, so none can be interpreted as a study result.

What analysis details are missing?

The registry record lists a primary outcome measure but no analysis results. It does not describe the statistical model, the confidence-interval method, handling of missing measurements, analysis population, or any adjustment for covariates. It also does not report interim analyses or a prespecified statistical plan. These omissions limit assessment of whether the analysis matched the endpoint definition and how uncertainty or incomplete observations were handled. The absence of these details does not establish that a particular method was or was not used; it means that method is not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Participants")
n      <- c(8)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Participants  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study tests or reports several outcomes, subgroups, time points, or comparisons. In general, conducting many statistical tests can increase the chance of observing an apparently notable result by chance. A prespecified analysis plan can clarify which endpoint is primary and whether adjustments or a hierarchy of tests are intended.

The registry record identifies one primary outcome measure, but reports no analyses. It does not state whether additional outcomes, subgroup analyses, repeated assessments, or multiple comparisons were planned, nor does it describe a multiplicity strategy. The protocol’s statistical analysis plan is not reported in the registry record. No conclusion about multiplicity adjustment can therefore be drawn.

Missing data also affect an incidence estimate. If some participants lack the measurements needed to classify the endpoint, the denominator and estimated percentage may depend on how those observations are handled. In general, excluding participants with incomplete measurements can bias an estimate if missingness is related to health status or outcome risk. Other approaches require assumptions that should be made explicit.

The registry record does not report missing-data counts, reasons for missingness, follow-up completeness, or a method for handling missing observations. It also does not identify an analysis population, such as all enrolled participants or only those with a complete endpoint assessment. Enrollment of 8 does not by itself establish how many participants contributed to an endpoint analysis. These details are not reported in the registry record, so the denominator and the effect of missingness cannot be assessed.

12. 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.

The registry safety summary lists 0 serious events affecting participants, 0 other events affecting participants, and 0 deaths. The group is labeled Participants, with 8 reported as at risk for each adverse-event category. These are safety-summary figures and should be read separately from the primary endpoint.

A count of 0 in a registry safety summary does not establish that there was no risk of an event. It records what was reported for this cohort and does not provide a precise estimate of the frequency of uncommon harms. The record does not give a confidence interval for these figures, describe safety surveillance procedures, or state the time window used for the adverse-event summary.

The primary endpoint is acute kidney injury meeting a specified creatinine threshold with no other obvious cause identified after clinical work-up. Serious adverse events and other adverse events are different reporting categories, so their counts cannot be used as a substitute for the primary endpoint result. The registry record does not list serious adverse-event terms. It also does not report a numerical analysis of anticoagulant-related nephropathy.

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

The record establishes that a completed cohort study focused on the incidence of anticoagulant-related nephropathy in relation to rivaroxaban. It specifies a 6-month endpoint based on acute kidney injury, a creatinine increase of at least 0.3 mg/dL, and the absence of another obvious cause after clinical evaluation. It also reports enrollment of 8 and a safety summary with 0 serious events, 0 other events, and 0 deaths.

The record does not report the primary outcome count, incidence percentage, confidence interval, or analysis. It therefore does not establish how often participants met the endpoint or how precisely that frequency was estimated. The safety figures do not fill this gap, because adverse-event reporting and the defined primary endpoint are not interchangeable.

The cohort description also does not document a comparator or random allocation. In general, observing an outcome in an exposed cohort is different from estimating the effect of exposure relative to an alternative. Without a documented comparison and analysis, the record cannot establish that rivaroxaban caused or prevented kidney injury, or quantify a difference from another treatment.

The study brief places the question in the context of prior concern about anticoagulant-related nephropathy, including discussion of warfarin and reports involving other oral anticoagulants. That background explains the rationale for studying rivaroxaban; it is not a result from the cohort. Likewise, COMPLETED status indicates the registered study is complete but does not mean its primary outcome has been posted.

Any planning illustrations based on an observed effect are planning exercises, not observed power and not clinical findings. Their assumptions include equal allocation between two arms, although the registry record does not document a two-arm randomized design. The appropriate reading is therefore limited: the registry states the question and endpoint, but the posted results do not answer the incidence question.

14. Why This Trial Matters Statistically

The trial matters statistically because it illustrates the difference between a clearly stated outcome definition and a reported estimate. The registry record defines a clinically assessed incidence endpoint with a laboratory threshold and an exclusion of other obvious causes. That specificity helps clarify what would count as an event, but it cannot show how many events occurred. Without a result and its uncertainty, readers cannot assess the estimated frequency or its precision.

The distinction between a cohort description and a controlled comparison is also important. The record identifies no comparator and does not state allocation. An observed incidence in a cohort can describe the participants followed, but it does not by itself identify what would have happened under another treatment or exposure. This limits causal interpretation regardless of the clinical interest of the question.

Enrollment of 8 makes precision and transparent reporting particularly important. In general, sparse data can yield substantial uncertainty, and a zero count in a safety category is not proof of zero underlying risk. The registry safety figures are informative as reported counts, but they do not substitute for an endpoint analysis or an uncertainty interval.

Finally, planning assumptions should not be mistaken for the study’s actual design or evidence of adequacy. The listed planning illustration assumes two arms with equal allocation and a normal approximation, while the registered study is described as a cohort without a comparator. Recognizing that mismatch helps prevent a hypothetical sample-size calculation from being read as a randomized-trial result. The registry record does not report a primary outcome analysis or a protocol-based sample-size justification.

15. 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 primary limitation for interpreting this study is that the registry record does not report a numerical result for its primary endpoint. Although the endpoint is defined and the study is marked COMPLETED, no event count, incidence percentage, confidence interval, or analysis is reported. The central question therefore remains unanswered by the posted results.

The record reports enrollment of 8, but does not provide participant characteristics, eligibility criteria, recruitment details, or the endpoint-analysis denominator. It is not possible to assess how representative the cohort was or whether all enrolled participants were followed and assessed. Follow-up is specified as 6 months, but the schedule and completeness of outcome measurement are not reported in the registry record.

Outcome classification depends on a creatinine threshold and a clinical determination that no other obvious cause was identified. The registry record does not describe how often creatinine was measured, how alternative causes were evaluated consistently, or whether outcome assessments were independently reviewed. Those details could affect whether cases were detected and classified uniformly.

No comparator is identified, and allocation is not stated. The record therefore does not establish a like-for-like control comparison. Information about treatment duration, adherence, concomitant care, and changes in exposure is also not reported in the registry record. These limitations prevent assessment of treatment contrasts and potential confounding.

The analysis plan, handling of missing data, analysis population, and methods for estimating uncertainty are not reported in the registry record. The planning assumptions describe equal allocation between two arms, which is not the design documented for the cohort. Finally, the safety summary’s zero counts do not resolve the missing primary outcome and do not quantify rare-event uncertainty.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Can Rivaroxaban Lead to Anticoagulation-Related Nephropathy? — NCT02900170.
• Registry record last updated 2020-07-07; status last verified 2020-06.
• Results first posted 2020-06-24.
• 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.

19. Record Summary

NCT02900170 is a completed cohort study titled Can Rivaroxaban Lead to Anticoagulation-Related Nephropathy? The listed condition is acute kidney injury, and enrollment is reported as 8. The primary endpoint is incidence of anticoagulant-related nephropathy over 6 months, based on acute kidney injury with a serum creatinine increase of at least 0.3 mg/dL and no other obvious cause found after standard clinical evaluation.

The primary endpoint result and statistical analysis are not reported in the registry record. No comparator or allocation method is identified. The safety summary reports 0 serious events, 0 other events, and 0 deaths. The record does not report the analysis population, missing-data handling, uncertainty estimates, or protocol-based sample-size justification.