The SAPIEN 3 Ultra System in Intermediate Risk Patients With Symptomatic, Severe Aortic Stenosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The SAPIEN 3 Ultra System in Intermediate Risk Patients With Symptomatic, Severe Aortic Stenosis (NCT03471065), a na na study. The primary outcome is Procedural Success.

2. Clinical Question

The study asks whether procedural success was observed after transcatheter aortic valve replacement using the SAPIEN 3 Ultra System in patients with severe, calcific aortic stenosis who were considered at intermediate operative risk for standard aortic valve replacement. Its primary endpoint is a count of participants meeting a definition of success at the end of the procedure-room period. The record also lists major vascular complications and valve migration or embolization as secondary outcomes.

This design describes outcomes among participants who received the device; it does not estimate a difference against another treatment or a control group. The registry record does not report the observed count for the primary endpoint, so the magnitude and precision of the procedural-success result cannot be assessed from the recorded primary outcome information.

3. Trial Design

This was a prospective, single-arm, multicenter study of a device for aortic valve replacement. Its official title describes participants with severe, calcific aortic stenosis at intermediate risk. The registry lists 100 participants enrolled and identifies transcatheter aortic valve replacement as the study arm. The study status is completed. The recorded dates are a start date of 2018-06-01 and a primary completion date of 2019-12-23.

Because the study has a single group and no like-for-like control arm, its principal descriptive role is to report outcomes among those who received the SAPIEN 3 Ultra System. The record lists allocation as NA and masking as none. It also lists phase as NA. These registry entries do not establish an allocation procedure or a blinded assessment process beyond what is recorded. A randomized treatment contrast, comparison with standard surgery, or estimate of relative effect cannot be derived from this design.

The primary outcome is procedural success, expressed as a participant count and assessed at Day 0. Success is defined by freedom from all of three specified events at exit from the procedure room: mortality, conversion to surgery, and moderate or severe paravalvular regurgitation. The registry also names major vascular complications and valve migration or embolization among the secondary outcomes. It records three outcome measures in total, but does not list a statistical analysis record.

The study's brief summary says it will confirm procedural safety and performance in this population. That aim is not itself evidence that confirmation was achieved. The registry record does not report a prespecified statistical plan, a sample-size justification, or the result for the primary outcome. Without a comparator, observed outcomes can describe the study cohort but cannot separate the device's contribution from other influences or support a causal comparison with an alternative strategy.

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

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 Procedural Success, measured over Day 0.

The primary endpoint counts participants with procedural success at Day 0. The registry defines success as freedom from all of the following at exit from the procedure room: mortality, conversion to surgery, and moderate or severe paravalvular regurgitation. This is a composite definition: a participant must avoid each listed event to meet the success criterion. The endpoint therefore focuses on the immediate procedural result rather than a longer-term clinical outcome.

A participant count is a direct way to describe how many people met a specified outcome definition. It is useful for communicating the observed frequency of a procedural outcome in the treated group, provided the count and its denominator are available and the endpoint definition is applied consistently. The registry states the outcome unit as participants, but does not report the number meeting the success definition or a corresponding proportion. It is therefore not possible to describe the observed success frequency or its precision from the primary outcome entry.

Composite endpoints can summarize several clinically distinct events in a single measure, but the components may differ in nature and importance. A composite result alone would not show which component occurred most often; component-specific results would be needed for that interpretation. The record gives the defining components but does not report their individual primary-endpoint counts. The use of a procedure-room time point also limits the scope of the endpoint: it addresses events through that point, not outcomes over later follow-up.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical task in this study would be to describe a binary participant-level outcome: whether each participant met the procedural-success definition. For a binary outcome, the observed data can be expressed as the number meeting the definition and the number assessed. The registry identifies the endpoint as a count of participants, but does not report the count meeting the definition. Without that numerator, neither the observed success proportion nor an interval around it can be interpreted.

What a confidence interval would describe

In general, a confidence interval quantifies uncertainty around an estimated quantity under a specified statistical method and its assumptions. For a single-group binary endpoint, an interval could describe uncertainty in the cohort's underlying success frequency. It would not create a comparison group or remove possible bias in who entered the study, how the outcome was assessed, or how missing observations were handled. The registry record does not report a confidence interval, the method for calculating one, or a statistical analysis plan for the primary endpoint.

Why the single-group structure matters

A one-group study can summarize outcomes among participants receiving the device, but it cannot directly estimate the difference between the device and another intervention. A contrast requires outcome information for a comparator group and a defined method for comparing groups. No concurrent comparator is listed, and allocation is recorded as NA. Therefore, a treatment-effect estimate, comparative p-value, or randomized contrast is not available from this design. Comparisons with external experience would require additional data and assumptions not described in the registry record.

Reading the adverse-event summaries

The adverse-event record gives the number at risk and the number affected for serious and other adverse events in the TAVR group. These are descriptive counts. A participant may experience more than one event or event term, and a person may appear in more than one category; the registry does not specify the overlap. For that reason, the serious-event count, other-event count, death count, and term-specific percentages should be read as separate summaries rather than components that can automatically be combined. The record does not give a time-at-risk denominator or details sufficient to turn these summaries into event rates over follow-up.

For general context, over-dispersion matters when a statistical model assumes that variation is limited by a particular probability distribution but the observed data vary more than that assumption allows. In such cases, uncertainty estimates from an overly restrictive model can be too small. This is a general concept, not a reported feature or analysis of this study. The registry record lists no analysis model, so there is no basis for stating whether over-dispersion was assessed or relevant to an analysis.

Planning illustrations are not trial results

The described planning approach is explicitly an illustration based on an observed effect, rather than the trial's own design. It specifies a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation; it also describes detecting stated fractions of the observed effect. For time-to-event planning, the approach uses a total event count, while other planning outputs are expressed as participants per arm. These assumptions do not turn this single-group study into a two-arm trial and should not be mistaken for its actual enrollment plan.

In general, sample-size planning estimates how much information a hypothetical study might need to detect a chosen effect under stated assumptions. The output depends on the effect size, variability, significance threshold, desired power, allocation, and analysis method. A planning calculation is not observed evidence, and it is not observed power. The registry record does not report the trial's own sample-size justification, a power target, or a prespecified effect for the primary endpoint. No numerical planning output is available in the record described for this study, so no participant requirement can be inferred.

What is not documented

The registry record does not report an inferential method for the primary endpoint, an adjustment strategy, an interim-analysis plan, or a handling rule for missing data. It also does not list analysis records. Without these details, readers cannot determine whether the endpoint was analyzed exactly as defined, whether exclusions occurred, or how uncertainty was quantified. These gaps do not prove that such procedures were absent from the conduct of the study; they mean that they are 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("Transcatheter Aortic Valve Replacement (TAVR)")
n      <- c(100)
events <- c(100)
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  Transcatheter Aortic Valve Replacement (TAVR)  100  100  100.0  96.4  100.0  96.3  100.0  96.4  100.0

11. Multiplicity, Missing Data and Analysis Populations

The study record lists three outcome measures, identifies procedural success as the primary endpoint, and names major vascular complications and valve migration or embolization as secondary outcomes. It does not report how testing across outcomes was handled. When several outcomes are assessed, the chance of at least one apparently notable finding can increase if each is tested separately without a multiplicity strategy. This is a general statistical concern; no adjustment method, testing hierarchy, or other multiplicity plan is reported in the registry record.

The primary endpoint definition combines freedom from mortality, conversion to surgery, and moderate or severe paravalvular regurgitation. The record gives the composite definition but does not provide component-specific results. It therefore does not show whether any participant failed the composite because of a particular component, nor how the components were summarized statistically. The listed secondary outcomes are named, but their results are not included in the registry information.

Missing-data handling can affect estimates if participants lack outcome assessments or if missingness is related to their outcomes. The registry record does not report whether primary outcome observations were incomplete, how missing values were treated, or which analysis population was used. It also does not provide a participant flow or an accounting of exclusions from the primary analysis. These points remain unknown rather than evidence that data were missing or that a particular approach was used.

The registry lists no analysis records. It does not report an interim-analysis plan or a statistical analysis plan. Accordingly, the available record does not establish the timing or rules for any formal analyses, whether multiplicity was controlled, or how the primary and secondary outcomes were prioritized analytically. These reporting gaps limit reproducibility and interpretation of the planned inferential framework, but they do not establish what procedures may have been used outside the registry record.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrioventricular block complete (7.0%), bundle branch block left (3.0%), vascular access site haemorrhage (3.0%), ischaemic stroke (3.0%), atrioventricular block first degree (2.0%).

For the transcatheter aortic valve replacement group, the registry lists 100 participants at risk for serious adverse events, with 28 affected. It separately lists 100 at risk for other adverse events, with 14 affected, and records one death. The serious adverse-event terms with the highest listed percentages include complete atrioventricular block at 7.0%, left bundle branch block at 3.0%, vascular access site haemorrhage at 3.0%, ischaemic stroke at 3.0%, first-degree atrioventricular block at 2.0%, and vascular access site haematoma at 2.0%.

These figures are descriptive summaries for the study group, not comparative estimates. The registry does not state whether participants could contribute multiple events or appear under more than one adverse-event category, so counts and percentages should not be summed to create a total. It also does not state whether the death is included in the serious-adverse-event count. The record does not give details on event timing, duration, severity criteria beyond the serious classification, or the relationship of events to the device. The figures therefore describe what the registry reports, while leaving these contextual questions unresolved.

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

The record establishes that this was a completed, prospective, multicenter, single-group study enrolling 100 participants with aortic valve stenosis. Its stated aim was to confirm procedural safety and performance of the SAPIEN 3 Ultra System in participants with severe, calcific aortic stenosis at intermediate operative risk. The primary endpoint is defined clearly enough to identify what would count as procedural success and when it would be assessed: at exit from the procedure room on Day 0.

The primary outcome result itself is not reported in the registry record. Consequently, the available information does not show how many participants met the procedural-success definition, how frequent success was, or how precisely that frequency was estimated. The registry does report serious and other adverse-event counts and one death, along with selected serious-event terms and percentages. Those summaries describe events in the treated group, but they do not show how event occurrence compares with another treatment or with a control group.

A single-group study can document outcomes experienced by participants who received an intervention. It cannot, by itself, determine what would have happened to comparable participants under a different strategy. Differences in underlying risk, clinical care, participant selection, and outcome assessment cannot be separated from the intervention's contribution without an appropriate comparison and analysis. The absence of a comparator does not invalidate descriptive observations; it limits the questions those observations can answer.

The posted information also does not establish the precision of the primary endpoint estimate, because no primary count or interval is recorded. It does not report a statistical analysis plan, missing-data method, or analysis population. These limitations mean the registry record cannot support a detailed inferential assessment of procedural success. The findings should be understood as registry-reported design and safety summaries, not as proof of a comparative effect or as a complete account of the study's statistical analysis.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary question is framed as a participant-level procedural outcome in a single-group device study. The endpoint has an explicit composite definition and a specific time point, which helps clarify what the intended outcome represents. At the same time, the absence of a reported primary count means that a clearly defined endpoint is not enough on its own: interpretation also depends on the result, denominator, and uncertainty estimate being available.

The single-group design illustrates the difference between describing an outcome and estimating a treatment contrast. Counts among participants who received a device can inform a descriptive account of procedural experience. They do not show whether outcomes would differ under an alternative treatment. This distinction matters especially when a study's stated aim concerns safety and performance: descriptive findings and comparative evidence answer different statistical questions.

The adverse-event entries also show why denominators and category definitions matter. Counts for serious and other events, a death count, and percentages for selected event terms each convey different information. Without details on overlap, event timing, and the relationship between categories, they should not be combined into a single total or interpreted as comparative rates. Clear reporting of those details can make safety summaries easier to assess.

Finally, the registry record lists no analysis records and does not report the primary endpoint result, the analysis population, missing-data handling, multiplicity strategy, or sample-size justification. These are not minor technical details: they shape how readers assess uncertainty, reproducibility, and the scope of conclusions. The record illustrates why a protocol-level question, an observed result, and an inferential analysis need to be distinguishable in clinical-trial reporting.

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 most direct limitation of the registry information is that the primary outcome is defined but its observed count is not reported. Without that result, the central procedural-success question cannot be answered from the registry record, and no estimate of its precision can be evaluated. The record also does not provide component-specific outcomes for mortality, conversion to surgery, or moderate or severe paravalvular regurgitation.

The single-group design has no concurrent control for comparing outcomes. Thus, the study record cannot provide a randomized or like-for-like estimate of the difference between the SAPIEN 3 Ultra System and another treatment. The enrollment of 100 participants describes the cohort size, but it does not by itself establish that the study had adequate precision for the primary endpoint; the registry record does not report the trial's sample-size justification.

For safety, the record gives participant counts and selected term percentages but does not explain overlap among categories, event timing, duration of follow-up for these summaries, or the relationship of the recorded death to the intervention. Major vascular complications and valve migration or embolization are named as secondary outcomes, but their results are not reported in the information available. The serious-event percentages should be read as listed, without summing them or treating them as a comprehensive safety profile.

Analysis methods and populations are also not documented in the registry record. It does not report missing-data handling, exclusions, confidence intervals, a multiplicity strategy, interim analyses, or an analysis plan. These are reporting limitations; they do not establish that the study lacked procedures for addressing them. They constrain what can be reproduced or inferred from the registry entry alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The SAPIEN 3 Ultra System in Intermediate Risk Patients With Symptomatic, Severe Aortic Stenosis — NCT03471065.
• Registry record last updated 2025-05-18; status last verified 2025-05.
• Results first posted 2021-01-19.
• 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

The registry record describes NCT03471065, a completed, prospective, multicenter, single-group study of the SAPIEN 3 Ultra System in patients with symptomatic, severe, calcific aortic stenosis at intermediate operative risk. Enrollment was 100. The intervention was the SAPIEN 3 Ultra Delivery System with the SAPIEN 3 Ultra THV for transcatheter aortic valve replacement; allocation is listed as NA and masking as none.

The primary endpoint was procedural success at Day 0, defined as freedom from mortality, conversion to surgery, and moderate or severe paravalvular regurgitation at exit from the procedure room. Its observed count is not reported in the registry record. The registry lists 28 participants with serious adverse events among 100 at risk, 14 with other adverse events among 100 at risk, and one death. It names major vascular complications and valve migration or embolization as secondary outcomes. No analysis records are listed, and statistical methods, missing-data handling, and the trial's sample-size justification are not reported.