CONFIDENCE Registry to Assess Safety and Performance of Portico System to Treat Patients With Severe Aortic Stenosis.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CONFIDENCE Registry to Assess Safety and Performance of Portico System to Treat Patients With Severe Aortic Stenosis. (NCT03752866), a non-randomized na study. The primary outcome is Cardiovascular Mortality.

2. Clinical Question

3. Trial Design

CONFIDENCE is a completed, non-randomized clinical registry evaluating Portico transcatheter aortic valve implantation. The registry describes a sequential study model with no masking. It records enrollment of 1001 and identifies two groups according to the delivery system used: the Portico delivery and loading system, or the FlexNav delivery and loading systems. Both groups received the Portico valve.

Because treatment allocation was not randomized, the groups should not be interpreted as exchangeable by design. A direct difference between their outcomes would not, on its own, isolate an effect of the delivery system. The registry explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The selection process for each system and any adjustment for differences between participants are not reported in the registry record.

The record gives a study start date of 2018-10-25, a primary completion date of 2021-11-02, and a completed status. The stated purpose is to characterize procedural safety and device performance in participants with symptomatic degenerative aortic stenosis. The primary endpoint is cardiovascular mortality at 30 days from the index procedure. Secondary outcomes include counts of participants with myocardial infarction, stroke, bleeding events, acute kidney injury, vascular complications, annular rupture, coronary obstruction, and conversion to open surgery. The registry lists 21 outcome measures overall.

The record does not report a detailed statistical analysis plan, a sample-size justification for the registry, or how participants were assigned to a delivery-system group. The study’s sequential model and observational allocation describe its structure; they do not establish that changes over time or group differences can be attributed to a device configuration.

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: The number of participants analyzed includes subjects who were available at that time of analysis

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 Cardiovascular Mortality, measured over 30 days from the index procedure.

The primary endpoint is the count of participants with cardiovascular mortality at 30 days from the index procedure. The registry defines cardiovascular mortality broadly: it includes death due to a proximate cardiac cause, non-coronary vascular conditions, procedure-related deaths, valve-related deaths, sudden or unwitnessed death, and death of unknown cause. The analysis population is described as participants available at that time of analysis.

As a safety endpoint, mortality captures an outcome with clear clinical importance and avoids treating less consequential events as equivalent to death. Including several specified causes also makes the endpoint broader than a narrow count of deaths attributed only to a single cardiac mechanism. That breadth can be useful when evaluating procedural safety, although interpretation depends on consistent cause classification and complete follow-up. Those classification and follow-up procedures are not reported in the registry record.

The registry gives no primary endpoint count, estimate, or uncertainty interval. Accordingly, the posted information does not show the observed 30-day cardiovascular-mortality result, nor does it establish how precisely that result was estimated. The adverse-event death counts are separate posted figures and should not be substituted for the primary endpoint: their definitions and relationship to the cardiovascular-mortality endpoint are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a registry study records outcomes among participants receiving care in the setting described, rather than assigning treatment through randomization. Here, the record identifies non-randomized allocation and a sequential model. That means the system groups are descriptive cohorts, not randomized arms. Participants in one group may differ from those in the other in ways related to system selection, timing, clinical characteristics, or practice. Whether any such differences occurred, and how they were handled analytically, are not reported in the registry record.

What does a count endpoint tell the reader?

The primary outcome is expressed as a count of participants with cardiovascular mortality, with a defined 30-day timeframe. A count conveys how many outcome events were recorded in the analysis population, but its interpretation depends on the number of participants assessed and on outcome ascertainment. For a comparison, counts alone are not enough: the groups’ denominators, follow-up, and analysis approach matter. The record says that the number analyzed includes participants available at the time of analysis, but it does not report the primary count or the corresponding analysis details.

In general, a proportion places an event count in relation to the number assessed, while an uncertainty interval describes the precision of that estimate. A confidence interval is not a guarantee that the true value lies within its limits; it is an interval produced by a method with stated long-run coverage properties when its assumptions hold. No primary-outcome estimate or confidence interval is reported in the registry record, so its precision cannot be assessed from the posted primary results.

Why does non-random allocation matter?

Randomization is commonly used to balance, on average, known and unknown prognostic factors between study groups. Without randomization, descriptive group differences can reflect participant selection or other differences, not only the device configuration. Statistical adjustment can sometimes address measured differences, but it cannot automatically remove unmeasured confounding. The registry record does not report an adjusted analysis, covariates, or a method for estimating a comparative effect. The posted group counts should therefore be read as descriptive, not as a causal estimate.

In general, the sequential model describes the order or structure in which groups are included; it does not by itself establish a statistical comparison or control for changes over time. Masking is recorded as none. The record does not explain whether outcome assessors were independent or whether outcome classifications were reviewed under a particular procedure. Those details are not reported in the registry record.

What do the planning illustrations represent?

The planning illustrations are described as calculations based on an observed effect, not as the registry’s original design justification. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The illustrations consider detecting a stated share of the observed effect. For non-time-to-event outcomes, they are expressed as participants per arm for 80% or 90% power; time-to-event illustrations instead give a total number of events.

Such calculations are planning scenarios. They do not describe the number of participants or events actually observed, and they are not observed power. Observed power is not a substitute for examining an effect estimate and its uncertainty. The registry record does not report the original sample-size rationale, the assumptions behind the original enrollment target, or the calculations used in the study’s own design. The planning assumptions should not be mistaken for the trial’s prespecified analysis plan.

In general, over-dispersion matters when variation in outcome counts exceeds what a chosen statistical model expects. Ignoring it can make uncertainty estimates too narrow. The primary endpoint is a count of participants, and the record does not report an over-dispersion estimate or a model addressing it. There is therefore no basis to describe the primary analysis as having used a particular count model, variance correction, or distributional assumption.

What can be inferred from the posted analyses?

The registry lists no analysis entries. This does not establish that no analyses were conducted outside the registry; it means that analysis results are not reported in the registry record. There are no posted primary-outcome estimates, inferential tests, or adjusted comparisons to interpret. In general, a p-value addresses compatibility of data with a specified null model and assumptions; it does not measure effect size or clinical importance. No primary p-value is reported, and none should be inferred from the descriptive event summaries.

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("Portico™ Valve, Delivery System(s) and Loading Sys", "Portico™ Valve, FlexNav Delivery and Loading Syste")
n      <- c(501, 500)
events <- c(15, 6)
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  Portico™ Valve, Delivery System(s) and Loading Sys  501  15  3.0  1.7  4.9  1.8  4.9  1.8  4.9
ARM  Portico™ Valve, FlexNav Delivery and Loading Syste  500  6  1.2  0.4  2.6  0.6  2.6  0.6  2.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 21 outcome measures, including the primary cardiovascular-mortality endpoint and secondary safety outcomes such as myocardial infarction, stroke, bleeding events, acute kidney injury, vascular complications, annular rupture, coronary obstruction, and conversion to open surgery. When a study evaluates multiple outcomes, the chance of obtaining at least one apparently unusual result can increase if many tests are conducted. In general, multiplicity procedures can control a chosen error rate, but the appropriate approach depends on the analysis plan and the role of each outcome.

The registry record does not report whether any multiplicity adjustment was planned or used, how outcomes were prioritized beyond the stated primary endpoint, or which analyses were designated confirmatory. It lists no analysis entries. Therefore, there are no posted inferential results for which the handling of multiple comparisons can be assessed.

The record describes the primary analysis population as participants available at that time of analysis. It does not explain how unavailable participants were handled, whether missing outcome status was imputed, or whether follow-up completeness differed between groups. It also does not report an analysis population definition beyond availability at the relevant analysis time. Missing-data assumptions and sensitivity analyses are not reported in the registry record.

In general, excluding participants without observed outcomes can affect interpretation if outcome availability is related to prognosis or group membership. The direction and size of any such effect cannot be determined without details on missingness and analysis. The posted safety counts should not be assumed to include all participants throughout an identical follow-up period unless the registry record specifies that.

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: complete heart block (11.8%), other (6.8%), infection (4.2%), death - unknown (3.6%), stroke (3.2%).

The adverse-event summary reports serious adverse events for each delivery-system group. In the Portico delivery-system group, 348 participants are listed as affected, with 501 at risk; in the FlexNav group, 358 are listed as affected, with 500 at risk. The corresponding counts for other adverse events are 72 with 501 at risk and 80 with 500 at risk. These are separate summaries and should not be combined.

The serious-event terms listed include Complete Heart Block (11.8%), Other (6.8%), Infection (4.2%), Death - Unknown (3.6%), Stroke (3.2%), and Congestive Heart Failure (3.0%). The registry record does not explain the denominator used for these percentages or whether a participant could contribute to more than one term. They should be read as reported term percentages, not reinterpreted as group-specific risks.

In general, a serious adverse event is a classification of event seriousness, not a statement that every such event has the same clinical course or relationship to a device. The registry record does not report an event-level assessment of causality or the time window for these adverse-event summaries. It also lists deaths of 16 and 10, but does not specify that these counts represent cardiovascular mortality at 30 days. They should not be treated as the primary endpoint result.

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

The record describes a completed observational registry of Portico valve implantation using two delivery-system configurations. It documents the study’s safety and device-performance purpose, the endpoint definitions, and adverse-event summaries. Those details can help readers understand what outcomes were intended to be captured and how the study groups were organized.

The record does not report the primary cardiovascular-mortality count, an estimate of its frequency, or an uncertainty interval. It therefore does not establish the observed primary outcome or its precision. The adverse-event counts are descriptive, and the non-randomized allocation prevents treating the groups as randomized controls. A difference in their reported counts would not by itself show that one delivery system caused more or fewer events.

The information also does not establish whether the observed safety experience is attributable to the valve, delivery system, participant characteristics, procedural practice, or other factors. The registry record does not report comparative adjustment, an analysis plan, or sufficient details about missing outcomes to support those conclusions. The death counts in the adverse summary cannot be substituted for the defined primary endpoint.

In general, a registry can describe outcomes in a clinical setting and identify patterns that warrant careful assessment. Its evidential strength for comparative causal claims depends on design, outcome ascertainment, completeness of follow-up, and analysis. The registry record supports a description of the registered study and posted safety counts, but not a claim of superiority, equivalence, or treatment effect between the delivery-system groups.

14. Why This Trial Matters Statistically

This registry is statistically important to read as an observational device study rather than as a randomized head-to-head trial. Its non-randomized allocation and sequential model shape what the group summaries can establish. Descriptive counts can characterize the recorded experience, but they do not automatically estimate what would have happened had comparable participants received the other delivery system.

The study also illustrates why the endpoint definition and analysis population matter. Cardiovascular mortality is defined using several causes and is assessed at 30 days from the index procedure. The record specifies that the number analyzed includes participants available at the time of analysis, but does not report the primary count or detail the handling of unavailable participants. Without both outcome information and analysis context, the precision and completeness of the primary result cannot be evaluated.

The range of listed secondary safety outcomes reflects that device assessment can involve multiple types of events. In general, multiple outcomes raise questions about which analyses were planned as primary, how statistical errors were controlled, and whether reported findings are exploratory or confirmatory. Those details are not reported in the registry record, which lists no analysis entries.

Finally, the registry distinguishes its stated purpose—characterizing safety and performance—from a causal comparison. Keeping that distinction clear prevents descriptive safety counts, term percentages, or planning calculations from being mistaken for proof of a comparative effect. The posted record is informative about design and selected safety summaries, while leaving key inferential results and methods unreported.

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 for interpretation is that the registry record does not report the primary cardiovascular-mortality result. Although the endpoint definition and time frame are stated, there is no posted count, estimate, or uncertainty interval. The death counts in the adverse-event summary have no reported link to the primary endpoint definition and cannot fill that gap.

The comparison between delivery-system groups is limited by non-randomized allocation. The registry explicitly cautions that the groups are not like-for-like controls. It does not report how system choice was made, whether the groups differed at baseline, or whether any statistical adjustment was performed. Consequently, descriptive group counts cannot be interpreted as causal contrasts.

Further limitations arise from information not reported in the registry record: outcome ascertainment procedures, the analysis plan, missing-data methods, multiplicity handling, and detailed follow-up completeness. The primary analysis population is described only as participants available at the time of analysis. Without more detail, it is not possible to judge how unavailable participants may affect the reported safety summaries.

The serious-event term percentages are listed without a stated denominator or explanation of whether participants could appear under multiple terms. The adverse-event death counts also lack a reported time frame in the record. These omissions constrain comparisons across terms and prevent treating the adverse summary as a substitute for a defined mortality endpoint. The registry lists 21 outcome measures but no analysis entries, so inferential findings for the registered outcomes are not available in the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CONFIDENCE Registry to Assess Safety and Performance of Portico System to Treat Patients With Severe Aortic Stenosis. — NCT03752866.
• Registry record last updated 2024-10-21; status last verified 2024-10.
• Results first posted 2024-10-21.
• 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 CONFIDENCE Registry is a completed, non-randomized, unmasked, sequential study sponsored by Abbott Medical Devices. It records enrollment of 1001 and evaluates Portico valve implantation using the Portico delivery and loading system or the FlexNav delivery and loading systems. Its stated purpose is to characterize procedural safety and device performance in participants with symptomatic degenerative aortic stenosis.

The primary endpoint is cardiovascular mortality at 30 days from the index procedure. The registry record describes the endpoint and lists secondary safety outcomes, but does not report the primary endpoint result or analysis entries. Adverse-event summaries include counts for serious and other events, selected serious-event terms with percentages, and death counts. Because allocation was non-randomized and the record identifies the groups as not like-for-like controls, those summaries do not establish a causal comparison between delivery systems. Important analysis, missing-data, and multiplicity details are not reported in the registry record.