Safety and Effectiveness of Agent Paclitaxel-Coated PTCA Balloon Catheter. (AGENT Japan SV): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Effectiveness of Agent Paclitaxel-Coated PTCA Balloon Catheter. (AGENT Japan SV) (NCT04058990), a randomized na study. The primary outcome is Percentage of Participants With Events Included in the Primary Endpoint (Target Lesion Failure).

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked, parallel-group device trial comparing the Agent Paclitaxel-Coated PTCA Balloon Catheter with the SeQuent Please Drug Eluting Balloon Catheter. The official title describes a 2:1 randomized trial. The listed outcome groups contain 101 participants for Agent and 49 for SeQuent Please; the registry reports enrollment of 180. The primary endpoint population is described as participants who signed informed consent, enrolled, and were implanted with their assigned randomized study device.

The trial concerns treatment of a small-vessel de novo native coronary artery lesion. Both devices are paclitaxel-coated balloons, with different stated paclitaxel densities: 2.0 μg/mm² for Agent and 3.0 μg/mm² for SeQuent Please. The registry lists the trial phase as NA and its status as completed. The listed start date is 2019-12-12 and primary completion date is 2021-12-22.

The primary outcome is a binary participant-level measure: whether a participant experienced any event included in target lesion failure by 6 months post procedure. The registry identifies the analysis as non-inferiority and reports a Farrington-Manning analysis. The non-inferiority margin and detailed statistical analysis plan are not reported in the registry record. The registry record also does not report further details on masking procedures, treatment implementation, or the allocation process beyond describing the trial as randomized, single-masked, and parallel-group.

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

Analysis population for the primary outcome, as defined in the registry: Non-inferiority analysis - ITT population - all subjects who sign an Informed Consent Form, are enrolled in the trial, and are implanted with the assigned, randomized study device.

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: Data are reported separately for each cohort as pooled mean and standard deviations across cohorts do not provide meaningful data.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Events Included in the Primary Endpoint (Target Lesion Failure), measured over 6 months post procedure.

The primary endpoint is the percentage of participants with an event included in target lesion failure by 6 months post procedure. It is a participant-level binary outcome: each participant either experienced at least one qualifying event during the stated period or did not. The registry defines target lesion failure as ischemia-driven revascularization of the target lesion, myocardial infarction related to the target vessel (Q-wave or non-Q-wave), or cardiac death.

A combined endpoint can capture several clinically important types of failure in one measure. In general, such endpoints are useful when a trial seeks to assess a broader outcome than any one component alone. They also require careful interpretation: an overall result does not show which component contributed most, and components may differ in frequency or clinical meaning. Component-specific results are not reported in the registry record.

The registry reports counts of participants with events, rather than only a continuous measure. The endpoint’s stated timeframe is 6 months post procedure. Results outside that period, or longer-term follow-up for this endpoint, are not reported in the registry record. The registry calls the analysis non-inferiority, but the margin used to define an acceptable difference is not reported in the registry record. That missing design detail limits interpretation of what the non-inferiority test was intended to establish.

7. Results Posted in the Registry

• SeQuent Please Drug Eluting Balloon Catheter: 0.0% (0/49) versus 3.0% (3/101) on control; risk difference -3.0 percentage points (95% CI -6.3 to 0.3); unadjusted two-proportion z-test p = 0.223.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because it records whether each participant experienced at least one qualifying target lesion failure event within the specified follow-up. The posted group results are counts of participants with an event. For a binary endpoint, the risk is generally the proportion of participants experiencing the event in a group. A risk difference compares those group risks by subtraction. The recalculated risk difference is reported as -0.030 for SeQuent Please relative to Agent. The posted analysis does not adjust this recalculation for other variables.

What does a risk difference represent?

In general, a risk difference expresses an absolute contrast in event probability between groups. Its sign depends on the order of subtraction. A negative value for SeQuent Please relative to Agent corresponds to a lower observed event proportion in SeQuent Please in this recalculation. The estimate is not a relative risk, and it does not state how many events would occur in a different population. The estimate should be read with its uncertainty interval and the design context, rather than as a standalone measure.

What is the role of the confidence interval?

In general, a confidence interval describes the range of effect estimates compatible with the data under the statistical procedure used. It conveys precision as well as direction. For the recalculated risk difference, the interval runs from -0.063 to 0.003 and includes zero. This means the interval includes both a negative risk difference and values slightly above zero. The interval does not establish that the groups are equivalent, and it is not a probability statement about the true effect. The confidence level for this particular interval is not reported in the registry record.

How does non-inferiority differ from a usual difference test?

In general, a non-inferiority test compares an estimated treatment contrast with a prespecified margin. The margin defines the largest disadvantage that the design regards as acceptable for the non-inferiority question. A conventional test of no difference instead asks whether the data are inconsistent with a zero difference. These are different hypotheses, so a non-inferiority result cannot be inferred from an ordinary unadjusted p-value or from the direction of the observed event counts. The non-inferiority margin for this trial is not reported in the registry record.

The registry names the Farrington-Manning method for its non-inferiority analysis and reports p = 0.001. In general, the Farrington-Manning approach is used for testing non-inferiority between proportions while accounting for a specified margin. The registry does not report the margin, the analysis estimate, or a confidence interval for the sponsor’s test. The posted p-value therefore identifies the reported test result but does not provide the missing margin or quantify the contrast on its own.

Why can the recalculation differ from the sponsor analysis?

The recalculation is an unadjusted comparison derived from the posted summary counts. The registry’s named analysis is a Farrington-Manning non-inferiority test. The methods address different formulations of the comparison: the recalculation reports an ordinary risk difference and unadjusted p-value, while the sponsor analysis is explicitly framed as non-inferiority. The registry record marks a discrepancy between the analyses. Accordingly, the sponsor’s own analysis takes precedence; the recalculation is useful as a descriptive check on the posted counts, not as a replacement for the trial’s reported analysis.

For binary outcomes, sparse events can make estimates and tests sensitive to the method used. General statistical methods may use different assumptions or constraints, especially when one group has no observed events. Here, the SeQuent Please group has 0 events, while the Agent group has 3. The recalculation’s confidence interval and p-value should be understood as results of that unadjusted procedure, not as a substitute for the sponsor’s non-inferiority test.

What can be inferred from the analysis population?

The registry describes the primary endpoint as an ITT analysis population comprising participants who signed informed consent, enrolled, and were implanted with their assigned randomized device. This wording is the registry’s stated population definition. In general, intention-to-treat principles aim to preserve randomized group comparisons, but the record’s stated definition includes implantation and does not provide further detail on how participants without implantation or missing endpoint data were handled. Those details are not reported in the registry record.

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as a stated fraction of the observed effect. These are planning illustrations, not observed power and not a description of the trial’s original design justification. The trial’s own sample-size justification is not reported in the registry record.

10. Confidence Intervals and Precision

The recalculated risk difference is -0.030, with an interval from -0.063 to 0.003. The interval spans values on both sides of zero, so the estimate is not precise enough to rule out no difference under this unadjusted calculation. Its width also permits a range of negative differences, rather than identifying one narrowly determined effect. The confidence level for the interval is not reported in the registry record.

Precision is affected by the amount of information in the data and by how frequently the outcome occurs. In general, a binary outcome with few events tends to yield less stable comparisons than an outcome with many events. The posted results contain 3 events in the Agent group and 0 in the SeQuent Please group. With no events in one group, a change in only a few observed outcomes could meaningfully alter the estimated contrast. This is a reason to avoid treating the point estimate as a definitive measure of the underlying difference.

The sponsor’s Farrington-Manning analysis is reported with p = 0.001, but the registry does not report its estimate or confidence interval. The p-value alone does not show the range of plausible effect sizes, and the non-inferiority margin is not reported in the registry record. Thus, the sponsor result cannot be used to describe precision in the same way as the recalculated interval.

Planning illustrations in the registry are based on the observed effect, use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect described as a fraction of the observed effect. Such illustrations depend on assumptions and are not observed power. No numerical planning results are reported in the registry record. They should not be confused with evidence that the trial was adequately powered for its stated non-inferiority question.

11. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a Farrington-Manning non-inferiority test with p = 0.001. Separately, an unadjusted recalculation from the posted summary counts gives a risk difference of -0.030 for SeQuent Please relative to Agent, an interval from -0.063 to 0.003, and p = 0.223. These are not identical analyses: the recalculation is an unadjusted risk-difference comparison, whereas the sponsor analysis is explicitly a non-inferiority test. The registry record flags a discrepancy, so the sponsor’s own analysis takes precedence over the recalculation.

The sponsor’s reported p-value should be presented as the result of that named non-inferiority analysis, not substituted with the recalculated p-value. At the same time, p = 0.001 does not supply the non-inferiority margin, the estimated contrast, or its confidence interval. Those details are not reported in the registry record. Without the margin, readers cannot assess the exact threshold used for the non-inferiority question from the posted result alone.

The recalculation remains informative as a descriptive comparison of the posted counts, but it should not be framed as overturning the sponsor’s analysis. Nor should the sponsor’s p-value be treated as a complete account of effect size or precision. The record supports reporting both results with their distinct roles and the stated discrepancy.

12. Multiplicity, Missing Data and Analysis Populations

The registry record reports one primary endpoint and one analysis, and no secondary outcome results are posted. The number of secondary outcomes with posted results is recorded as 0. A list of all planned outcomes and their analysis hierarchy is not reported in the registry record. It is therefore not possible to determine from the record whether additional outcomes were planned but not posted, or how any such outcomes were intended to relate to the primary question.

Multiplicity arises in general when several outcomes, time points, subgroups, or statistical tests are examined. Repeated testing can increase the chance of finding an apparently notable result by chance unless the analysis plan addresses it. The registry record does not report a multiplicity adjustment or a broader testing strategy. That absence should not be taken as evidence that no such plan existed; the details are simply not reported in the registry record.

The posted primary population is described as an ITT population of participants who signed informed consent, enrolled, and were implanted with the assigned randomized device. The record does not provide further details about exclusions, adherence to assigned treatment, or how missing primary endpoint data were handled. It also does not report the number of participants with missing outcome status or a missing-data method. These omissions limit assessment of how closely the analyzed population and observed data align with the stated population.

In general, missing outcome data can affect a binary endpoint if the probability of missingness differs between groups or is related to the outcome. The available record does not establish whether such a problem occurred. The analysis population description and lack of missing-data detail therefore call for caution, not an assumption that data were missing or that the result was biased. The analysis plan, missingness patterns, and sensitivity analyses are not reported in the registry record.

13. 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: cardiac disorders (6.9%), gastrointestinal disorders (3.3%), vascular disorders (2.0%), hepatobiliary disorders (2.0%), injury, poisoning and procedural complications (2.0%).

The registry lists serious adverse events affecting 15 participants in the Agent group and 4 in the SeQuent Please group. It lists other adverse events affecting 46 participants in the Agent group and 20 in the SeQuent Please group. Deaths are recorded as 0 in each of these two randomized groups. These are descriptive safety counts; the registry record does not provide a statistical comparison for them in the information presented.

A separate group, “Agent DCB - Single Arm ISR Sub Study,” is listed with 3 participants affected by serious adverse events, 12 affected by other adverse events, and 1 death. This is a single-arm subgroup listing, not a third arm in the randomized comparison described for the primary endpoint. The record does not provide enough information to compare this group directly with either randomized group.

The registry lists serious adverse event terms with percentages: Cardiac disorders, 6.9%; Gastrointestinal disorders, 3.3%; Vascular disorders, 2.0%; Hepatobiliary disorders, 2.0%; Injury, poisoning and procedural complications, 2.0%; and Eye disorders, 1.0%. The registry excerpt does not specify the attribution of these term percentages to individual randomized groups. They should not be treated as arm-specific rates.

In general, adverse event counts depend on the definitions, observation period, and reporting procedures used. Further detail on event severity, timing, relatedness, and the denominators underlying the listed term percentages is not reported in the registry record. These figures describe recorded events and do not, by themselves, establish a causal relationship to a device.

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

The results describe a randomized comparison of two paclitaxel-coated balloon catheters for small-vessel de novo native coronary artery lesions, with target lesion failure assessed at 6 months post procedure. The posted primary endpoint counts are 3 participants with an event in the Agent group and 0 in the SeQuent Please group. The unadjusted recalculation reports a risk difference of -0.030 for SeQuent Please relative to Agent, with an interval from -0.063 to 0.003 and p = 0.223. The registry separately reports a Farrington-Manning non-inferiority p-value of 0.001, and that sponsor analysis takes precedence over the recalculation.

The results do not show that the devices are identical. In general, a failure to demonstrate a difference in an ordinary test is not evidence of equivalence, and a non-inferiority conclusion depends on a prespecified margin. The margin is not reported in the registry record. The sponsor’s non-inferiority p-value is recorded, but the associated estimate and confidence interval are not. Those omissions prevent a full assessment of the margin-based comparison from the registry result alone.

The endpoint combines target lesion revascularization, target-vessel-related myocardial infarction, and cardiac death. The overall count does not show how many events came from each component, because component-specific results are not reported in the registry record. The findings also do not describe outcomes beyond the stated six-month timeframe. Secondary outcome results are not reported in the registry record.

These data should not be extended to other lesions, procedures, populations, devices, or follow-up periods without evidence addressing those settings. Event counts are sparse, and the unadjusted interval is broad enough to include zero. The registry record also lacks details on the non-inferiority margin, missing data, and several aspects of the statistical plan. The appropriate reading is therefore limited to the recorded groups, endpoint, follow-up, and analyses—not a general claim about treatment benefit or lack of benefit.

15. Why This Trial Matters Statistically

This trial raises a central statistical issue in comparative device research: the distinction between testing for a difference and testing for non-inferiority. Those questions use different hypotheses and need different information for interpretation. The record names a non-inferiority analysis and reports its p-value, but does not report the margin. Without that threshold, a reader cannot evaluate the precise degree of disadvantage the study was designed to exclude.

The results also illustrate how sparse binary outcomes affect interpretation. There are 3 target lesion failure events in one randomized group and 0 in the other. Such counts make the observed comparison sensitive to a small number of outcomes. A point estimate may look directional, while its interval still covers values on either side of no difference. Reporting event counts, an effect estimate, and uncertainty together helps prevent overinterpretation of either the direction or the test result.

The sponsor’s analysis and the unadjusted recalculation answer differently framed statistical questions. The registry flags a discrepancy, and the sponsor’s own analysis takes precedence. Keeping the analyses distinct is important: replacing a margin-based non-inferiority test with an ordinary unadjusted comparison would change the inferential question, while citing the sponsor p-value without its missing margin and estimate would leave key context unclear.

Finally, interpretation depends on what is reported. The primary endpoint definition and population are stated, but component-specific outcomes, secondary results, missing-data handling, and the non-inferiority margin are not reported in the registry record. These gaps limit independent assessment of the analysis and show why a p-value alone is not a complete statistical account.

16. 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 main limitation for interpreting the primary result is that the registry does not report the non-inferiority margin. It also does not report the sponsor analysis’s effect estimate or confidence interval. Although the sponsor’s Farrington-Manning p-value is available and takes precedence over the recalculation, these missing details prevent an independent assessment of the margin-based contrast and its precision.

The endpoint event counts are sparse: 3 participants had events in the Agent group and 0 in the SeQuent Please group. Sparse outcomes can make estimates sensitive to individual observations. The unadjusted interval extends from -0.063 to 0.003, and the confidence level is not reported in the registry record. The recalculation is therefore a limited descriptive check, not a replacement for the sponsor’s analysis.

The record provides a specific primary population description, but does not explain how participants who were randomized but not implanted, or participants with missing outcome data, were handled. Missing-data counts, methods, and sensitivity analyses are not reported in the registry record. The record also does not give details of the randomization procedure, concealment, or masking implementation beyond its general design labels.

Target lesion failure combines several outcomes, but their separate counts are not reported in the registry record. The primary result is restricted to 6 months post procedure; longer follow-up is not reported. No secondary outcome results are posted. For safety, the registry lists adverse event counts and serious event terms, but does not report enough detail to establish event timing, relatedness, or arm attribution for the term percentages.

The record states that enrollment was 180, while the two primary endpoint groups list 101 and 49 participants. The registry excerpt does not explain the relationship between the enrollment figure and the endpoint group sizes. The trial’s sample-size justification and full statistical analysis plan are also not reported in the registry record.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Safety and Effectiveness of Agent Paclitaxel-Coated PTCA Balloon Catheter. (AGENT Japan SV) — NCT04058990.
• Registry record last updated 2026-07-23; status last verified 2026-07.
• Results first posted 2022-12-23.
• 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.

20. Record Summary

NCT04058990 is a completed randomized, single-masked, parallel-group device trial comparing Agent Paclitaxel-Coated PTCA Balloon Catheter with SeQuent Please Drug Eluting Balloon Catheter for small-vessel de novo native coronary artery lesions. The official title describes a 2:1 randomized trial. The registry lists enrollment of 180, a start date of 2019-12-12, and a primary completion date of 2021-12-22.

The primary endpoint is target lesion failure at 6 months post procedure, defined to include ischemia-driven target lesion revascularization, target-vessel-related myocardial infarction, or cardiac death. The registry reports 3 events among 101 participants in the Agent group and 0 among 49 in the SeQuent Please group. It reports a Farrington-Manning non-inferiority p-value of 0.001. An unadjusted recalculation gives a risk difference of -0.030, an interval from -0.063 to 0.003, and p = 0.223; because the registry flags a discrepancy, the sponsor’s own analysis takes precedence.

The non-inferiority margin, sponsor estimate and interval, missing-data handling, and secondary outcome results are not reported in the registry record. The posted findings are limited to the stated endpoint and follow-up.