Azilsartan Tablets Special Drug Use Surveillance: Long-term Use: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Azilsartan Tablets Special Drug Use Surveillance: Long-term Use (NCT02092025), a registered phase not stated study. The primary outcome is Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs).

2. Clinical Question

The surveillance was intended to assess the safety and efficacy of long-term azilsartan use among people with hypertension in routine clinical settings. Its primary endpoint focuses on adverse drug reactions, defined as adverse events that the investigator considered causally related to treatment. This makes the primary question about events attributed to the drug by investigators, rather than every unfavorable health event occurring during the observation period.

The registry also lists changes from baseline in systolic and diastolic blood pressure at each time point as secondary outcomes. However, numerical results for those outcomes are not reported in the registry record. The record identifies 3437 participants as enrollment, while the safety analysis set is described separately. The primary endpoint's numerical result is not reported in the registry record, so the documented aim can be described but its observed frequency cannot be evaluated from these registry entries.

3. Trial Design

This is a special drug use surveillance record for azilsartan tablets in people with hypertension. The stated purpose was to evaluate safety and efficacy during long-term use in routine clinical care. The record is marked COMPLETED. It gives a study start date of 2012-06-20 and a primary completion date of 2016-01-15, and lists enrollment of 3437.

The intervention was azilsartan, given as tablets at 20 mg - 40 mg orally once daily for up to 12 months. The dose was based on disease severity, and treatment was part of routine medical care. The registry record does not describe a comparator arm, and it does not state how participants were allocated. It therefore does not document a randomized comparison or a like-for-like control group. Comparisons between treated and untreated groups cannot be inferred from this record.

The safety analysis set included participants who received at least 1 dose of study drug. The serious adverse event figures use 3369 as the number at risk, as do the figures for other adverse events. Those figures should be understood within their stated safety context and not treated as the enrollment count or as the primary endpoint result.

The record lists a primary safety endpoint and secondary blood-pressure outcomes, but it does not report numerical results for the primary endpoint or those secondary outcomes. It lists 0 analyses. Information about the planned statistical analysis, sample-size justification, interim analyses, and handling of follow-up is not reported in the registry record. The design can therefore be described as routine-care surveillance, but its analytic plan and detailed conduct cannot be reconstructed from the recorded information.

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: Participants with a historical diagnosis of hypertension were enrolled to receive Azilsartan 20 milligram (mg) - 40 mg tablet, orally, once daily for up to 12 months.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis set included all participants who received at least 1 dose of study drug.

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.

Population: Safety Analysis set included all participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs), measured over Up to 12 Months.

The primary endpoint is the number of participants who experienced at least one adverse drug reaction during follow-up of up to 12 months. An adverse drug reaction is defined as an adverse event that, in the investigator's opinion, has a causal relationship to study treatment. An adverse event is defined as an unfavorable and unintended sign, symptom, or disease temporally associated with use of a medicinal product, reported from the first dose through the last dose of study drug.

This endpoint is used to describe the occurrence of treatment-attributed harm in the safety analysis set. Counting participants with at least one reaction focuses on whether a participant experienced an event, rather than how many separate events that participant experienced. It is therefore a participant-level count, not a count of all event episodes. The investigator's causal judgment is part of the definition, so the endpoint is not equivalent to a count of every event occurring during treatment.

The registry record does not report the numerical primary endpoint result. Consequently, the frequency of participants with at least one adverse drug reaction cannot be assessed from the posted results described in the record. The serious and other adverse event figures are separate safety summaries and should not be substituted for the primary adverse drug reaction endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a count of participants who experienced at least one adverse drug reaction. For a binary outcome, each participant is classified according to whether the defined event occurred. This differs from counting every event episode: a participant with repeated reactions still contributes to the endpoint as a participant who experienced at least one reaction. The registry record does not report the numerical count for this endpoint, so no event frequency can be described.

When a binary outcome is reported, the count is interpreted alongside the number of participants assessed. The resulting proportion describes how common the event was in that observed group. A confidence interval, when available, communicates uncertainty around an estimated proportion; it does not remove limitations in how the participants were selected, observed, or classified. No confidence interval for the primary endpoint is reported in the registry record.

Why does the endpoint definition matter?

The endpoint is restricted to adverse events that the investigator considers causally related to treatment. The broader adverse-event definition covers unfavorable and unintended signs, symptoms, or diseases temporally associated with use of a medicinal product. Temporal association alone does not establish causality. Requiring investigator attribution makes the primary endpoint more specific to suspected treatment reactions, but it also makes the result dependent on the judgments and practices used to assign causality. Details of any common adjudication procedure are not reported in the registry record.

The observation window runs from the first dose to the last dose of study drug, with the endpoint timeframe stated as up to 12 months. A participant's opportunity to have an event recorded depends on observation during treatment. The registry record does not describe the completeness of follow-up, event ascertainment procedures, or how observations after treatment ended were handled.

How should the safety counts be read?

The serious adverse event summary reports 10 affected participants among 3369 at risk. The other adverse event summary reports 15 affected participants among 3369 at risk. These counts describe the posted safety summaries; they do not provide an estimate of the primary adverse drug reaction endpoint. They also do not establish that an event was caused by azilsartan. The record's primary endpoint has a separate causal-attribution definition.

General statistical interpretation of a count requires attention to the denominator, the event definition, the observation period, and the analysis population. Counts without a comparison group describe what was recorded in the observed group; they cannot identify what would have happened under a different treatment. No comparative estimate or test of a treatment difference is reported in the registry record.

What can a planning illustration tell the reader?

A sample-size planning illustration is a calculation about the design of a hypothetical future comparison under specified assumptions. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a fraction of an observed effect. Such an illustration is not the study's observed power, does not show that the surveillance was designed with those assumptions, and does not provide an outcome result.

The record describes a routine-care surveillance group without a reported comparator. A planning scenario based on two arms is therefore distinct from the design information recorded for this surveillance. The actual sample-size justification and statistical plan are not reported in the registry record. Planning calculations should not be read as a substitute for a prespecified analysis or as evidence that an effect was detected.

Why are no inferential results described?

Inferential statistics such as confidence intervals and hypothesis tests need numerical outcome data and a defined analysis. The registry record lists 0 analyses and does not report a numerical result for the primary endpoint. Without those details, it is not possible to describe statistical significance, precision, or an adjusted treatment effect. This is a limitation of the record's reported information, not a finding that the endpoint was zero or that the study had no relevant observations.

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("Azilsartan")
n      <- c(3369)
events <- c(94)
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  Azilsartan  3369  94  2.8  2.3  3.4  2.3  3.4  2.3  3.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety outcome and secondary outcomes for changes from baseline in systolic and diastolic blood pressure at each time point. Examining multiple outcomes or multiple time points can increase the chance of observing an apparently notable result by chance if formal tests are performed. Statistical approaches to multiplicity can address that issue, but the appropriate approach depends on the planned analyses and the questions being tested. A multiplicity strategy is not reported in the registry record.

The record lists 0 analyses and does not report numerical results for the primary or secondary outcomes. It also does not report p-values, confidence intervals, adjusted estimates, or an analysis plan. It is therefore not possible to assess whether multiplicity adjustments were used or whether results were analyzed according to a prespecified hierarchy. The lack of reported results should not be interpreted as evidence that no tests were conducted outside the registry record.

The safety analysis set included participants who received at least 1 dose of study drug. That definition identifies who was eligible for the safety analysis, but it does not explain how incomplete outcome data were handled. The amount or pattern of missing data, reasons for missingness, and any imputation or sensitivity analyses are not reported in the registry record. The record also does not describe the analysis population for the secondary blood-pressure outcomes. These omissions limit assessment of whether the reported safety summaries represent complete observation of the eligible participants.

12. 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 0.4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: decreased appetite (0.0%), cerebral infarction (0.0%), loss of consciousness (0.0%), prinzmetal angina (0.0%), sinus arrest (0.0%).

The serious adverse event summary reports 10 participants affected among 3369 at risk. The summary for other adverse events reports 15 participants affected among 3369 at risk. The record also lists the following serious event terms, each reported as 0.0%: decreased appetite, cerebral infarction, loss of consciousness, Prinzmetal angina, sinus arrest, and bradycardia.

A displayed percentage of 0.0% does not necessarily establish that an event never occurred; a rounded percentage can display as 0.0% even when the underlying count is not zero. The registry record does not give event counts for these individual terms, so their counts should not be inferred from the displayed percentages. Nor do the serious event summaries establish that the events were caused by treatment. The primary adverse drug reaction endpoint uses an investigator's causal assessment and is not numerically reported in the registry record.

These safety figures describe recorded events in a routine-care surveillance setting without a reported comparator. They should not be interpreted as comparative risks or as proof of causation.

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

The registry record documents a surveillance study intended to assess long-term azilsartan safety and efficacy in routine clinical care among people with hypertension. It identifies the dose range, treatment route, follow-up timeframe, primary safety question, and safety analysis population. The reported serious and other adverse event summaries provide limited descriptive information about events recorded in the safety population.

The record does not report the numerical result for the primary endpoint, which is the number of participants experiencing at least one adverse drug reaction. It also does not report numerical changes in systolic or diastolic blood pressure. As a result, the posted information does not establish the observed frequency of the primary endpoint or the magnitude and precision of blood-pressure changes. No conclusion about a treatment effect can be drawn from an absent endpoint result.

The safety summaries are not a controlled comparison. No comparator group is reported, and allocation is not stated. Counts in a surveillance group cannot show how outcomes would compare under another treatment or without treatment. Furthermore, the primary endpoint depends on investigator attribution, while the event summaries do not by themselves identify causal relationships.

Accordingly, the study's stated purpose and recorded safety counts can be described, but they do not establish that azilsartan caused or prevented any particular outcome. The record also does not support a claim that the treatment is effective or ineffective. Interpretation is constrained by the missing numerical results, absent analysis details, and lack of a reported comparison group.

14. Why This Trial Matters Statistically

This record illustrates a distinction that matters in biostatistics: a study's stated objective and endpoint definition are not the same as a reported result. The registry describes a participant-level adverse drug reaction endpoint and a safety analysis set, but the primary endpoint count is not reported. Without the event count and its denominator for that endpoint, readers cannot assess its observed frequency or precision, even though the study's enrollment and other safety counts are recorded.

It also shows why safety outcomes need careful definitions. An adverse event is defined by its temporal association with medicinal product use, while an adverse drug reaction additionally requires the investigator's opinion that it is causally related to treatment. The two concepts are not interchangeable. Serious and other adverse event summaries can inform a descriptive account, but they do not replace the primary causal-attribution endpoint.

Routine-care surveillance can describe observations made in clinical practice, while a reported comparator and analysis plan are important for estimating treatment differences. Neither a comparison group nor a stated allocation method appears in this record. The record therefore serves as an example of how the scope of conclusions depends on what was measured and reported, not solely on enrollment size or study completion status.

Finally, planning assumptions should be kept separate from observed findings. A sample-size illustration based on an assumed two-arm comparison is a planning exercise, not evidence that a treatment effect was observed or that the surveillance had a particular power. This distinction is important when registry information is used to understand the strength and limits of a clinical evidence record.

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 endpoint is defined, but its numerical result is not reported in the registry record. Numerical results for the listed secondary blood-pressure outcomes are also not reported. This prevents assessment of the endpoint frequency, blood-pressure changes, and statistical precision.

No comparator group is reported, and allocation is not stated. The record therefore does not support a like-for-like comparison or an estimate of treatment differences. Although the surveillance took place in routine clinical care, the record does not describe participant selection, event ascertainment in detail, or whether follow-up was complete.

The primary endpoint relies on an investigator's opinion about whether an adverse event was causally related to treatment. Procedures for standardizing or reviewing attribution are not reported. Missing-data amounts, reasons for missingness, and methods for handling missing observations are also not reported in the registry record.

The safety analysis set is defined as participants who received at least 1 dose, and the adverse event summaries report 3369 at risk. The record does not explain the relationship between that safety denominator and enrollment of 3437. It lists 0 analyses and does not report a statistical analysis plan, multiplicity approach, sample-size justification, or interim analyses. These limits restrict interpretation to the study description and the posted safety counts rather than a detailed evaluation of treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Azilsartan Tablets Special Drug Use Surveillance: Long-term Use — NCT02092025.
• Registry record last updated 2019-01-15; status last verified 2018-07.
• Results first posted 2019-01-15.
• 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

This completed special drug use surveillance record concerns azilsartan tablets for hypertension in routine clinical care. Enrollment is listed as 3437. The study started on 2012-06-20, and primary completion is listed as 2016-01-15. Treatment was azilsartan 20 mg - 40 mg orally once daily for up to 12 months, with dose based on disease severity.

The primary endpoint was the number of participants with at least one adverse drug reaction. The safety analysis set included participants who received at least 1 dose. Serious adverse events were reported for 10 participants among 3369 at risk, and other adverse events for 15 among 3369 at risk. The primary endpoint result and numerical secondary blood-pressure results are not reported in the registry record. No comparator group or analysis is reported.