Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement (NCT01240902), a randomized na study. The primary outcome is Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality.

2. Clinical Question

The study’s stated purpose was to evaluate the safety and efficacy of the CoreValve System in people with symptomatic severe aortic stenosis who faced high or very high risk from aortic valve surgery. That broad purpose covers different clinical questions: outcomes following TAVI in extreme-risk participants, and a comparison of TAVI with surgery in high-risk surgical participants. The registry reports the outcomes separately. It does not report a single comparison spanning all participants, nor does it establish that the extreme-risk access categories were intended as a randomized comparison with one another.

The primary outcome is reported as a Kaplan-Meier percentage at 1 year. For extreme-risk participants, the outcome combines all-cause death or major stroke; for the high-risk surgical group, it is all-cause mortality. The registry describes the analysis population as participants with an attempted implant procedure. These definitions frame what the reported rates mean: they are not interchangeable measures, and the extreme-risk outcome includes a major stroke component that is not listed in the high-risk surgical primary outcome.

3. Trial Design

The Medtronic CoreValve® U.S. Pivotal Trial was a randomized, parallel-group study with no masking reported. The registry lists an enrollment of 1453 and identifies Medtronic Cardiovascular as the sponsor. The study is marked completed. Its start date is 2010-12-10, and its primary completion is recorded as 2014-08. The phase is listed as NA.

The registry describes two risk settings and several intervention arms. In the extreme-risk setting, TAVI is listed with iliofemoral access and with non-iliofemoral access. In the high-risk surgical setting, the listed arms are TAVI and surgical aortic valve replacement. This structure matters for interpretation: the primary outcome for extreme-risk participants is not the same as the mortality outcome used in the high-risk surgical comparison. The access groups should not be read as equivalent to the randomized TAVI-versus-SAVR comparison.

The registry states that the primary-outcome population consisted of all subjects with an attempted implant procedure. The listed primary results include 489 participants in the extreme-risk iliofemoral TAVI group, 150 in the extreme-risk non-iliofemoral TAVI group, 391 in the high-risk TAVI group, and 359 in the high-risk SAVR group. Those group counts describe the reported outcome groups; they should not be taken as a substitute for a full account of participant flow or analysis-population definitions.

The trial included 20 outcome measures and 13 analyses in the registry record. Secondary outcomes include cardiovascular and cerebrovascular events, major adverse events, permanent pacemaker implantation for conduction disturbance, functional measures, days alive and out of hospital, and quality of life. The registry record does not report the detailed randomization procedure, allocation concealment, a sample-size justification, or a full statistical analysis plan. It also does not report masking beyond stating that the study was unmasked.

Because the study spans distinct risk groups, access routes, and endpoint definitions, interpretation should preserve those distinctions. The results do not form a single four-arm test of one shared primary outcome. In particular, the 1-year all-cause death-or-major-stroke endpoint in the extreme-risk group should not be directly compared with the 1-year all-cause mortality endpoint in the high-risk surgical group as if they were the same measure.

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: The first 3 successfully enrolled and implanted iliofemoral subjects at each implanting site, inclusive of both the High Risk Surgical and Extreme Risk patient populations were considered roll-in subjects, and were automatically assigned to undergo Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI).

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participant Population= Consisted of all subjects with an attempted implant procedure.

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: Participant Population= As Treated (AT) cohort. The AT cohort consisted of all Intent to Treat (ITT) subjects with an attempted implant procedure.

6. Primary Endpoint

The registry lists the primary outcome as Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality, measured over 1 year.

The primary endpoint is defined differently for the two risk settings. For extreme-risk participants, it is the percentage experiencing all-cause death or major stroke by 1 year. For high-risk surgical participants, it is the percentage experiencing all-cause mortality by 1 year. The registry reports these as Kaplan-Meier estimates and defines the primary-outcome population as participants with an attempted implant procedure.

A combined outcome such as death or major stroke can capture more than one serious event type in a single measure. All-cause mortality, by contrast, counts death from any cause and does not include stroke as a separate component. These endpoints answer different questions, so the rates should be interpreted within their own risk group and endpoint definition rather than ranked across groups.

Kaplan-Meier estimation is a time-to-event approach. General explanation: it estimates the probability of remaining free of the event over follow-up while accounting for participants whose event status is not observed for the entire period. This is useful when follow-up duration varies or some participants are censored. The registry reports a 1-year timeframe but does not report the censoring details or the underlying event counts for these primary outcomes.

The registry lists an extreme-risk iliofemoral TAVI estimate of 26.0, with a 95% confidence interval from 22.3 to 30.1. The extreme-risk non-iliofemoral result is 39.3, but no confidence interval is listed for that estimate. The high-risk arms have reported primary outcome percentages of 14.1 for TAVI and 18.9 for SAVR, but the registry does not give their confidence intervals or a numerical effect estimate for that comparison. A confidence interval describes the statistical precision of an estimate; without one, precision cannot be assessed from the registry entry in the same way.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is presented as a Kaplan-Meier percentage at 1 year. General explanation: a Kaplan-Meier estimate uses the timing of events and censoring to estimate event experience over time, rather than simply dividing the number of observed events by the number enrolled. Censoring occurs when follow-up ends without an observed event or when an event status is otherwise no longer observed. The record does not report the censoring rules, number at risk over time, or event counts supporting the primary estimates.

What does the confidence interval convey?

The extreme-risk iliofemoral estimate is 26.0, with a 95% confidence interval from 22.3 to 30.1. General explanation: a confidence interval expresses the uncertainty around an estimate under the analysis assumptions. A narrower interval generally indicates greater statistical precision than a wider one. It is not a guarantee that the true value lies inside a particular interval, and it does not address biases arising from study conduct, endpoint definition, or missing information. No interval is listed for the extreme-risk non-iliofemoral estimate, and no primary comparison interval is listed for the high-risk surgical groups.

How should the reported tests be read?

The registry records one-sided z-tests for the extreme-risk iliofemoral result and for the high-risk TAVI non-inferiority analysis. It reports p < 0.001 for each. A p-value describes how compatible data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of a result. The registry does not report enough detail to identify all hypotheses and testing conventions, including the non-inferiority margin. In particular, a non-inferiority p-value cannot be fully interpreted without the margin and the effect estimate with its uncertainty.

What can recalculated secondary comparisons establish?

Some secondary comparisons are simple, unadjusted recalculations from posted summary statistics. For continuous outcomes, the calculations use group means and standard deviations; for the binary adverse-event outcome, they use group event proportions. General explanation: these methods estimate a contrast between groups and its sampling uncertainty under simplifying assumptions. They do not account for covariate adjustment, stratification, censoring, or other design features unless those are explicitly included. The registry does not report sponsor analyses for these secondary comparisons, so the recalculated p-values should not be treated as the trial’s prespecified confirmatory analyses.

The secondary comparison for days alive and out of hospital has a reported mean difference of 0.06 between high-risk TAVI and the extreme-risk iliofemoral group, with a 95% interval from 0.028 to 0.092 and an unadjusted p-value of p < 0.001. The corresponding high-risk TAVI and extreme-risk group membership differs, so this is not the randomized high-risk TAVI-versus-SAVR comparison. For the high-risk TAVI versus iliofemoral group comparison of index procedure-related major adverse events, the recalculated risk difference is -0.009, with an interval from -0.075 to 0.057 and an unadjusted p-value of 0.792. Such estimates describe the stated group contrast and should not be interpreted as proof of equivalence.

Why do sample-size illustrations differ from trial power?

The planning illustrations use the observed effect or a stated fraction of it, two-sided significance level 0.05, equal allocation, and a normal approximation. General explanation: these are hypothetical design calculations showing how many participants per arm might be needed to detect an assumed effect under those assumptions. They are not observed power, do not show the probability that this completed trial detected an effect, and are not evidence that the trial was designed around those effects. The registry record does not report its original sample-size justification. The illustrations also do not incorporate a full account of the trial’s actual allocation, missingness, endpoint analysis, or multiplicity strategy.

For comparisons based on continuous outcomes, the recalculations use a mean difference and pooled standard deviation. For binary outcomes, they use a risk difference. General explanation: effect estimates express the magnitude and direction of a contrast, while confidence intervals show the range of values compatible with the data under the model. When an interval includes zero for a difference measure, the data are compatible with values on either side of no difference at the chosen confidence level; that does not prove the groups are equivalent. Conversely, a small p-value does not by itself establish that an effect is important.

The registry lists 20 outcome measures and 13 analyses, but the full analysis plan, hierarchy of secondary outcomes, adjustment for multiple testing, and handling of missing outcome data are not reported in the registry record. Those omissions constrain how far statistical conclusions can go beyond describing the posted estimates and the limited analyses recorded.

10. Analyses Reported by the Sponsor

The registry lists sponsor-reported primary analyses for the extreme-risk iliofemoral group and the high-risk TAVI non-inferiority assessment. For the iliofemoral group, the listed estimate is 26.0, with a 95% confidence interval from 22.3 to 30.1 and a one-sided z-test p-value of p < 0.001. For the high-risk TAVI non-inferiority analysis, the record lists p < 0.001 but does not provide an effect estimate, confidence interval, or non-inferiority margin.

The registry also lists 39.3 for the extreme-risk non-iliofemoral group, without a reported inferential analysis. It gives 14.1 for high-risk TAVI and 18.9 for high-risk SAVR, but does not provide a numerical primary treatment contrast or its confidence interval. Consequently, the sponsor’s recorded high-risk test cannot be independently reconstructed from the posted primary summaries.

The recalculated comparisons elsewhere concern secondary outcomes, not a replacement analysis of the primary endpoints. They use unadjusted methods and do not reproduce a sponsor analysis, because no sponsor analyses are listed for those secondary comparisons. There is no recorded discrepancy between sponsor analyses and recalculations. The sponsor’s primary results and the recalculated secondary results therefore address different statistical questions and should be kept distinct. The registry record does not report the full protocol or analysis plan needed to evaluate whether the sponsor’s reported tests followed prespecified procedures.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 20 outcome measures and 13 analyses. It does not report a multiplicity strategy, such as a hierarchy of hypotheses, an adjustment method, or a distinction between confirmatory and exploratory secondary outcomes. This matters because interpreting many separate tests at their unadjusted thresholds can make apparently noteworthy findings more likely by chance. General explanation: multiplicity procedures control or contextualize the error associated with testing multiple hypotheses. Without a reported strategy, secondary p-values are best treated as unadjusted evidence rather than as a set of independent confirmations.

The full statistical analysis plan is not reported in the registry record. The record also does not report the sample-size justification, interim analyses, or the details of the non-inferiority design, including its margin. Those omissions prevent a complete assessment of whether the analyses and decision criteria were set before results were known. The trial is marked randomized and unmasked, but details of sequence generation, allocation concealment, and any stratification are not reported in the registry record.

The primary analysis population is described as participants with an attempted implant procedure. The record does not give a full participant-flow account or explain how participants without an attempted procedure, incomplete follow-up, or missing outcome measurements were handled. It does not report missingness by group, reasons for missing data, or sensitivity analyses. General explanation: missing data can affect estimates when the chance of missingness is related to outcomes or participant characteristics; the direction and magnitude of any effect depend on the missingness pattern and analysis assumptions.

For the Kaplan-Meier primary outcomes, the registry does not report censoring details, event counts, or numbers at risk across follow-up. Those details are important for assessing the basis and precision of time-to-event estimates. For the high-risk non-inferiority result, the absence of a reported margin and effect interval also limits independent interpretation. The posted results can be described, but these reporting gaps mean that a comprehensive evaluation of multiplicity, missingness, and analysis-population sensitivity is not possible from the registry record alone.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemias nec (46.7%), heart failures nec (23.9%), cardiac conduction disorders (21.7%), renal failure and impairment (20.7%), supraventricular arrhythmias (19.3%).

The registry lists serious adverse events affecting 452 of 489 participants in the extreme-risk iliofemoral TAVI group, 142 of 150 in the extreme-risk non-iliofemoral TAVI group, 346 of 390 in the high-risk TAVI group, and 324 of 357 in the high-risk SAVR group. These are counts of participants affected according to the registry fields, not a measure of the number of separate event episodes. The record does not provide a statistical comparison for these group counts.

Among the listed serious adverse-event terms, the record includes Anaemias Nec at 46.7%, Heart Failures Nec at 23.9%, Cardiac Conduction Disorders at 21.7%, Renal Failure And Impairment at 20.7%, Supraventricular Arrhythmias at 19.3%, and Pneumothorax And Pleural Effusions Nec at 18.8%. The registry does not specify the denominator or provide enough detail in these summaries to infer whether categories overlap, how events were adjudicated, or how exposure time was handled.

These safety figures are descriptive. Differences across the groups cannot be attributed to treatment from these counts alone, particularly because the groups include different risk settings and access categories. The registry record does not report deaths in the adverse-event summary fields. The figures should therefore be read as recorded safety information, not as a complete comparative safety analysis.

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

The primary results describe one-year event estimates in distinct clinical groups. In the extreme-risk iliofemoral TAVI group, the recorded Kaplan-Meier estimate for all-cause death or major stroke is 26.0, with a 95% confidence interval from 22.3 to 30.1. The extreme-risk non-iliofemoral group has a listed estimate of 39.3, without an interval or a reported test. In the high-risk surgical group, the listed all-cause mortality values are 14.1 for TAVI and 18.9 for SAVR, with a sponsor-reported non-inferiority test but without the comparison estimate, interval, or margin.

These results do not establish a direct comparison between the two extreme-risk access categories, nor do they allow the extreme-risk outcome to be compared as though it were identical to high-risk all-cause mortality. They also do not supply enough detail to independently verify the non-inferiority analysis. The p-values reported by the registry do not state the size or clinical importance of an effect, and the missing estimates and design details limit interpretation.

The secondary outcomes provide additional descriptive information and some unadjusted recalculations. Those analyses may help frame questions about function, hospital use, and procedure-related events, but they are not a substitute for complete prespecified primary analyses. Since multiplicity and missing-data procedures are not reported, isolated secondary p-values should be interpreted cautiously.

General explanation: statistical evidence and clinical importance are related but distinct. An estimate describes an observed outcome or contrast; its uncertainty describes how precisely it is estimated under stated assumptions. Neither alone determines whether a result matters to an individual or how a treatment should be chosen. The registry summaries do not provide a basis for medical advice. They document outcomes in the trial groups and the extent of statistical information recorded, with important gaps in the detail needed for broader conclusions.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and population boundaries are central to clinical-trial interpretation. The registry places results from extreme-risk participants and high-risk surgical participants within one study record, but their primary questions differ. One is a combined death-or-major-stroke outcome in extreme-risk TAVI recipients; the other is all-cause mortality in a high-risk TAVI-versus-SAVR comparison. Treating those outcomes as one common measure would obscure what was actually evaluated.

It also highlights the distinction between a reported p-value and a fully interpretable treatment effect. The registry records a non-inferiority p-value for the high-risk comparison, but does not provide the margin, effect estimate, or confidence interval. Without those elements, readers cannot assess the size and precision of the contrast or independently reconstruct the decision rule. A reported test is useful information, but it is not a complete account of the evidence.

The secondary results demonstrate another common statistical challenge: multiple endpoints can offer a broad view of outcomes while also complicating inference. Unadjusted comparisons can be informative, but a multiplicity plan is important when many outcomes and tests are considered. Here, the registry lists numerous outcomes and analyses but does not report how they were prioritized or adjusted.

Finally, this record shows the value of distinguishing registry summaries from a full trial report. The entry includes group-level estimates and selected analyses, but leaves several methods details unreported, including the sample-size justification, missing-data handling, and full analysis plan. Recognizing those limits is part of sound statistical interpretation: the reported numbers can be described precisely without overstating what they establish.

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.

Several limitations specific to this registry record affect interpretation. The primary endpoint differs between the extreme-risk and high-risk surgical settings, so comparisons across those settings are not like-for-like. The extreme-risk access groups have different reported estimates, but the registry does not provide a direct comparison or establish random allocation between access routes. The group values therefore cannot be used to infer an access-route effect from this record alone.

The primary results are incomplete for independent assessment. The extreme-risk non-iliofemoral estimate has no confidence interval or reported p-value. For the high-risk surgical comparison, the record lists values for both groups and a non-inferiority p-value, but does not report the numerical treatment contrast, interval, or non-inferiority margin. Event counts, numbers at risk, and censoring details are also not reported for the Kaplan-Meier outcomes.

The registry does not report the detailed statistical analysis plan, multiplicity strategy, original sample-size justification, or interim analyses. It does not describe missing-data handling, full participant flow, or sensitivity analyses. Details of randomization and allocation concealment are not reported, and no masking was used. These omissions limit assessment of bias, precision, and whether the reported analyses followed prespecified procedures.

Secondary comparisons are unadjusted recalculations from summary statistics, and sponsor analyses are not listed for those outcomes. They may not reflect adjustment or design features used in any fuller analysis. The adverse-event summaries also lack details about event adjudication, exposure time, category overlap, and denominators for the listed term percentages. These issues do not invalidate the recorded figures, but they constrain conclusions drawn from them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement — NCT01240902.
• Registry record last updated 2022-10-25; status last verified 2022-10.
• Results first posted 2015-06-08.
• 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

NCT01240902, the Medtronic CoreValve® U.S. Pivotal Trial, was a randomized, parallel-group, unmasked study marked completed. It enrolled 1453 participants with symptomatic severe aortic stenosis at high or very high surgical risk. The listed interventions were CoreValve System TAVI and surgical aortic valve replacement.

The primary outcome was assessed at 1 year, but its definition differed by risk setting: all-cause death or major stroke for the extreme-risk TAVI group, and all-cause mortality for the high-risk surgical TAVI-versus-SAVR comparison. The registry includes sponsor-reported primary tests, selected secondary outcomes, and serious adverse-event summaries. It does not report several details needed for full independent evaluation, including the complete analysis plan, multiplicity and missing-data procedures, and key components of the non-inferiority comparison.