EDWARDS INTUITY Valve System CADENCE-MIS Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for EDWARDS INTUITY Valve System CADENCE-MIS Study (NCT02672553), a randomized na study. The primary outcome is Median Subject Time Spent on Cardiopulmonary Cross Clamp.

2. Clinical Question

3. Trial Design

The registry record identifies this as a completed, randomized, parallel-group study with no masking. The recorded enrollment was 100. The trial compared the EDWARDS INTUITY Valve System, Model 8300A, with stented aortic bioprostheses. Its stated purpose was to compare the INTUITY system used with a minimally invasive surgical approach against commercially available aortic bioprostheses used with standard full sternotomy surgery.

The primary outcome was median subject time spent on cardiopulmonary cross clamp, measured in minutes at the time of surgery. The registry describes the timeframe as “At time of surgery; an average of 1 hour.” The primary analysis population is described as subjects with available data and as based on the AI cohort. The registry record does not report how the AI cohort was defined or how it relates to all randomized participants.

The numbers analyzed for the primary outcome were 46 in the INTUITY group and 48 in the control group. These endpoint analysis counts do not by themselves explain why the analysis counts differ from the recorded enrollment. Reasons for unavailable endpoint data, participant flow between randomization and analysis, and the handling of missing values are not reported in the registry record.

Secondary outcomes covered functional class, pressure gradients, effective orifice area, paravalvular leak, valve conversion during surgery, thoracic resternotomy, and permanent pacemaker use. The registry lists 28 outcome measures and 26 posted secondary outcomes. The specific valve models in the comparator group, details of treatment allocation procedures, and additional protocol methods are not reported in the registry record.

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: Three (3) of the subjects randomized to the Edwards INTUITY group were converted to the control group and received a commercially available surgical aortic heart valve via MIS and therefore these three (3) subjects could not be accurately categorized into the MIS-AVR or FS-AVR category and were excluded from the as intended (AI) cohort.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The outcome is reported for subjects where data is available. Analysis is based on the AI cohort

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: 3 of the subjs. randomized to the Edwards INTUITY group were converted to the control group and rec'd commercially available surgical aortic heart valves.From the overall,2 randomized to Edwards INTUITY \&1 randomized to control group were screen failures prior to procedure \& were excluded in the baseline analysis.Analysis is based on the AI cohort

6. Primary Endpoint

The registry lists the primary outcome as Median Subject Time Spent on Cardiopulmonary Cross Clamp, measured over At time of surgery; an average of 1 hour.

The primary endpoint is median time spent on cardiopulmonary cross clamp during surgery, measured in minutes. Cross-clamp time describes how long the aorta is clamped during cardiac surgery while blood flow is directed to an artificial heart and lung machine. The registry uses this time as a procedural measure for comparing the two surgical approaches and valve groups.

The reported median was 35.0 minutes for the INTUITY group, with a full range of 16.0 to 115.0 minutes. For the control group, the median was 47.5 minutes, with a full range of 32.0 to 123.0 minutes. The sponsor-reported median difference was -12.5 minutes. These are summaries of the observed endpoint values; the full ranges describe the lowest and highest recorded values, not the precision of the median estimate.

As a general statistical point, a procedural time endpoint can summarize the duration of a specific part of an operation and permit a direct comparison between groups. It does not, on its own, establish differences in other outcomes, such as recovery, symptoms, or longer-term health. The registry record does not report a confidence interval for the primary median difference, so its precision cannot be assessed from an interval estimate in the posted primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary comparison test?

The sponsor reports a Wilcoxon (Mann-Whitney) analysis for the primary endpoint, with the parameter described as the median difference in final values. As a general statistical explanation, the Wilcoxon-Mann-Whitney test ranks observations across the two groups and evaluates whether values in one group tend to be higher or lower than those in the other. It does not require the data to follow a normal distribution. It is often described as a test of medians, but that interpretation requires additional conditions, such as similarly shaped group distributions. If the shapes differ, the test can reflect broader distributional differences rather than a simple shift in medians.

The posted summaries are medians and full ranges, and the reported group comparison is a median difference of -12.5 minutes with p < 0.001. The registry does not report a confidence interval for this difference. A confidence interval, as a general concept, gives a range of values compatible with the data under the method used; it helps convey estimation precision in a way that a p-value alone cannot. The range from 16.0 to 115.0 minutes and the range from 32.0 to 123.0 minutes are observed full ranges, not confidence intervals.

How should the p-value be read?

As a general explanation, a p-value measures how surprising data at least as incompatible with a null hypothesis as the observed data would be, assuming that null hypothesis and the analysis model. It does not give the probability that the null hypothesis is true, nor does it measure the probability that the result occurred by chance in an ordinary-language sense. The sponsor-reported p < 0.001 is strong evidence against the no-difference null for this comparison under the test used. It does not quantify the clinical importance of the observed time difference.

The registry record does not report the exact test implementation, any adjustment variables, or a confidence interval for the primary comparison. No alternative primary analysis is reported. The primary endpoint is identified as a median and the comparison method is rank-based, but the record does not supply distributional diagnostics or other details that would show how the method’s assumptions were assessed.

What do the binary-outcome calculations represent?

The secondary valve-conversion outcome is reported as a count of participants. The posted counts are 3 of 49 in the INTUITY group and 0 of 48 in the control group. The unadjusted recalculation expresses the between-group contrast as a risk difference of 0.061, with a 95% confidence interval from -0.006 to 0.128 and p = 0.082. As a general explanation, a risk difference is the difference between the proportions with an event in two groups. The interval describes uncertainty in that estimated contrast under the recalculation method; because it includes zero, the data are compatible with no difference as well as with a range of nonzero differences. This simple calculation is not a substitute for any adjusted or prespecified sponsor analysis.

For outcomes with sparse counts, estimates can be imprecise and methods can behave differently, especially when one group has no recorded events. The registry record does not report a sponsor comparison for this secondary endpoint. The recalculated estimate is unadjusted and should be read as a descriptive comparison rather than as evidence that the registry’s planned analysis, if any, used this method.

Why do sample-size calculations need assumptions?

As a general statistical explanation, a sample-size calculation estimates how many participants would be needed to detect a chosen effect under specified assumptions. The planning illustration associated with the results uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not results observed in the trial. The registry record does not report the trial’s own sample-size justification, the effect size targeted at design, or whether the planning illustration matches the original protocol.

Sample-size planning is not the same as observed power. Once the data have been collected, the observed effect estimate and its uncertainty are more informative than a retrospective power calculation. The registry record reports an enrollment of 100, but that figure alone does not show how the enrollment target was chosen or whether recruitment matched the initial plan.

Why can variability matter?

As a general statistical explanation, the spread and shape of outcome data affect both the precision of estimates and the performance of statistical methods. Time measurements may be skewed or include extreme values; medians and rank-based methods can be useful summaries and tools in that setting. The full ranges indicate that observed times varied in each group, but ranges alone do not describe the distribution or quantify the standard error. Over-dispersion, when variation exceeds what a simple model assumes, can make model-based uncertainty estimates too narrow if the model is not adapted. The registry record does not report a dispersion estimate beyond the full ranges for this endpoint.

For the other outcomes, the registry includes measures with different data types, including counts, functional class, and measurements over time. A single statistical method would not necessarily suit all of them. The registry record does not report the analysis methods for every secondary outcome, details of repeated-measures modelling, or whether adjustment for baseline measurements was used. These missing details limit the ability to assess how each estimate was produced and how comparable the secondary findings are.

10. Analyses Reported by the Sponsor

The primary comparison reported by the sponsor uses the Wilcoxon (Mann-Whitney) method and identifies the result as a median difference in final values. It reports a median difference of -12.5 minutes and p < 0.001, alongside group medians of 35.0 minutes and 47.5 minutes. There is no separate recalculated primary estimate in the registry record to compare with the sponsor’s result. The sponsor’s reported analysis is therefore the primary inferential result available for this endpoint.

The unadjusted recalculation relates to the secondary valve-conversion outcome, not to the primary cross-clamp endpoint. It gives a risk difference of 0.061, a 95% confidence interval from -0.006 to 0.128, and p = 0.082. The registry record does not post a sponsor-reported statistical comparison for that outcome. Because the methods and endpoint differ, the secondary recalculation neither confirms nor contradicts the sponsor’s primary analysis.

For the primary outcome, the registry does not provide a confidence interval or additional details that would permit an independent reconstruction of the sponsor’s rank-based analysis. The sponsor’s reported result should be kept distinct from the simple unadjusted calculations for a binary secondary outcome.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary endpoint and lists 28 outcome measures, with 26 secondary outcomes posted. It records two analyses. The registry record does not report a multiplicity plan describing how the primary and secondary outcomes were prioritized, whether secondary tests were adjusted, or whether testing followed a hierarchy. Without that information, the evidential weight of multiple secondary findings cannot be judged as if each were an isolated, prespecified test.

Missing-data information is limited. The primary outcome is described as reported for subjects with data available and as based on the AI cohort. The endpoint analysis counts are 46 and 48, while the trial enrollment is recorded as 100. The registry record does not report reasons for unavailable primary values, the handling of missing values, or whether analyses were conducted under additional analysis-population definitions. It also does not explain the AI cohort designation. For adverse events, the recorded denominators differ by group and outcome category; further details about missing safety follow-up are not reported in the registry record.

Randomization is recorded, but the registry record does not report the sequence-generation method, allocation concealment, or whether any analysis adjusted for prognostic factors. Masking is recorded as none. The record does not report interim analyses, stopping rules, the trial’s sample-size justification, or a full statistical analysis plan. These omissions do not demonstrate that such procedures were absent; they mean their use cannot be established from the registry information.

As a general statistical point, missing observations can affect a comparison when availability is related to treatment group or outcome. Complete-case summaries describe participants with observed data, but may not represent all randomized participants if missingness is selective. Interpretation therefore depends on participant flow, reasons for missingness, and sensitivity analyses. Those details are not reported in the registry record, limiting assessment of the robustness of the posted endpoint result.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: muscular skeletal / dermatologic - other (12.5%), pleural effusion - bilateral (10.2%), arrhythmia - paroxysmal atrial fibrillation (paf) (8.3%), bleeding - cardiovascular - major (8.2%), pericardial tamponade - major (6.2%).

The adverse-event figures describe counts of participants in each group and should be read separately from the primary cross-clamp result. Serious adverse events were recorded for 31 of 49 participants in the INTUITY group and 27 of 48 in the control group. Other adverse events were recorded for 27 of 49 and 30 of 48, respectively. Deaths were recorded for 4 participants in each group. These are descriptive counts; the registry record does not report a statistical comparison for these figures in the registry record.

The listed serious-event terms include musculoskeletal or dermatologic other events at 12.5%, bilateral pleural effusion at 10.2%, and paroxysmal atrial fibrillation at 8.3%, along with other listed terms. The registry record does not provide further detail about event severity definitions, timing, duration, relatedness to the intervention, or the denominators underlying each listed percentage. The term frequencies do not show whether participants experienced more than one event.

As a general statistical point, safety counts can be uncertain, particularly when the number of participants is limited or follow-up differs. The counts alone do not establish a causal relationship or support a broad comparison of overall safety.

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

The primary result shows a difference in observed median cross-clamp time between the study groups: 35.0 minutes for the INTUITY group and 47.5 minutes for the control group. The sponsor reports a median difference of -12.5 minutes and p < 0.001 using a Wilcoxon (Mann-Whitney) analysis. This indicates a statistically detectable separation in the reported primary comparison under that method.

The result does not, by itself, show the size of the uncertainty around the median difference because a confidence interval is not reported. It does not establish why the times differed, or whether any difference in this procedural endpoint is accompanied by differences in other outcomes. The ranges describe the observed minimum and maximum times; they are not uncertainty intervals for the group medians.

The trial compared a particular valve system and surgical approach with commercially available stented bioprostheses used with standard full sternotomy. It does not isolate the effect of the valve from the effect of the surgical approach, because the study purpose links each group to a different approach. The registry record does not report further details that would clarify how these components were separated or controlled.

Secondary outcomes and safety counts add information about other recorded measures, but the registry record does not provide a complete statistical analysis plan or multiplicity strategy. The results therefore should not be collapsed into a single claim about comparative performance across all clinical outcomes. The primary endpoint is a measure of procedural duration, not a direct measure of long-term function or patient experience.

As a general statistical point, statistical significance and clinical importance are different questions. The p-value does not establish that an observed difference matters to patients, and the posted primary result does not state a threshold for a clinically important difference. The registry record also does not report longer-term outcomes beyond the listed secondary measures in a way that supports a comprehensive assessment of the groups.

14. Why This Trial Matters Statistically

This trial illustrates why a clinical comparison needs to be read at the level of its specific endpoint. Its primary measure is a surgical process time: median time on cardiopulmonary cross clamp. That is a distinct type of outcome from symptoms, valve measurements, subsequent procedures, or adverse events. A statistically strong result for a procedural measure should not be treated as a substitute for evidence on those other domains.

The design also pairs the valve groups with different surgical approaches: minimally invasive surgery for the INTUITY system and standard full sternotomy for the commercial bioprosthesis group. This is important for interpretation because the comparison, as described, concerns the strategies as a whole. The registry record does not report details that would allow the valve and approach contributions to be separated.

Statistically, the reported median difference and rank-based test provide complementary information: one describes the observed contrast and the other assesses the distributional comparison under a null model. The absence of a confidence interval for the primary difference leaves its estimation precision less fully described. The endpoint analysis counts and available-data wording also make participant flow and missing-data handling relevant to interpretation.

The registry’s range of secondary outcomes demonstrates the challenge of interpreting multiple endpoints. Different outcome types require appropriate methods, and multiple unadjusted tests can produce isolated findings that are not persuasive on their own. A prespecified outcome hierarchy and transparent analysis plan would help readers distinguish confirmatory questions from exploratory ones, but those details are not reported in the registry record.

These points matter beyond this study: sound interpretation depends on understanding what was randomized, what was measured, how much information was available, and how uncertainty was reported. The registry result is informative about the recorded primary procedural endpoint, while the broader comparative questions require evidence and methods beyond that single result.

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.

A central limitation is that the primary comparison combines a valve system with a minimally invasive approach and a commercial bioprosthesis with standard full sternotomy. The registry record does not describe a design that separates the influence of the valve from the influence of the surgical approach. Thus, the posted comparison is best understood as a comparison of the described treatment strategies, not as an isolated device effect.

The primary analysis is based on subjects with available data in the AI cohort, but the registry record does not define that cohort or explain why the primary analysis includes 46 and 48 subjects when recorded enrollment is 100. Reasons for missing endpoint data and sensitivity analyses are not reported. The precision of the primary median difference is also difficult to assess because no confidence interval is posted.

The control group is described as commercially available stented aortic bioprostheses, without identifying the specific models. The registry record does not report further procedural details, baseline characteristics, or information about how treatment allocation was concealed. Masking is recorded as none. These gaps restrict assessment of comparability, possible bias, and the extent to which results might apply to other settings.

There are multiple secondary outcomes, but the registry record does not report a multiplicity plan or complete statistical methods for each outcome. The available secondary information should therefore be interpreted cautiously. Adverse-event figures are also descriptive in the available record; further details about follow-up, event adjudication, and event relatedness are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: EDWARDS INTUITY Valve System CADENCE-MIS Study — NCT02672553.
• Registry record last updated 2019-01-28; status last verified 2018-08.
• Results first posted 2019-01-28.
• 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 identifies NCT02672553 as a completed randomized, parallel-group study with no masking and recorded enrollment of 100. The study compared the EDWARDS INTUITY Valve System, Model 8300A, used with a minimally invasive surgical approach, with commercially available stented aortic bioprostheses used with standard full sternotomy.

The primary endpoint was median cardiopulmonary cross-clamp time during surgery. Reported medians were 35.0 minutes and 47.5 minutes, with a sponsor-reported median difference of -12.5 minutes and p < 0.001 from a Wilcoxon (Mann-Whitney) analysis. The primary analysis included 46 and 48 subjects with available data.

Secondary outcomes addressed functional class, valve measurements, procedural events, and later interventions. Adverse-event counts and selected serious-event terms are also recorded. Details of the statistical analysis plan, multiplicity handling, missing-data methods, and primary confidence interval are not reported in the registry record.