Clinical Evaluation of MDT-2111 in Subjects With Small Aortic Annuli and Symptomatic Severe Aortic Stenosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Evaluation of MDT-2111 in Subjects With Small Aortic Annuli and Symptomatic Severe Aortic Stenosis (NCT01634269), a na na study. The primary outcome is Composite Score of Change in New York Heart Association (NYHA) Class and Effective Orifice Area (EOA)..

2. Clinical Question

The study concerns subjects with small aortic annuli and symptomatic severe aortic stenosis who were deemed difficult for surgical intervention. Its stated objective was to evaluate the safety and effectiveness of MDT-2111 in this population. The primary endpoint combines a functional measure with an anatomical measure, assessed from baseline to 6 months.

This question is descriptive for the treated group. Without a concurrent control group, the registry results cannot estimate a treatment-versus-control difference. The endpoint also requires both its functional and anatomical components; a result for only one component would not establish whether the composite criterion was met.

3. Trial Design

NCT01634269 is a completed study sponsored by Medtronic Cardiovascular. The listed official title is Medtronic MDT-2111 CoreValve Japan 23mm Study. The registry record lists the phase as NA, allocation as NA, and masking as none. It describes a single-group model and an enrollment of 20.

The intervention is MDT-2111 TAVI 23 mm. The record identifies subjects treated through Iliofemoral and Direct Aortic access, with separate as-treated safety groups for each route and an all-subjects group. These route groups are not described as randomized comparisons, and the record cautions that the arms are not a like-for-like control comparison. Differences between their counts should not be interpreted as comparative evidence about access routes.

The listed study start is 2012-07, primary completion is 2014-02, and status is completed. The primary endpoint is assessed at baseline and 6 months in implanted subjects. The registry lists 39 outcome measures and one analysis for the primary measure. It also names NYHA class over time and MACCE among secondary outcomes, with each label appearing repeatedly in the outcome list. The registry record does not provide further details in these entries about the time-specific secondary analyses.

The record does not report a protocol-level statistical plan, the rationale for the enrollment target, or details of interim analyses. Those elements should not be inferred from the single-group design or from later planning illustrations. Because no randomized comparator is listed, the principal interpretation is the observed experience in the treated study group, not a causal comparison with another treatment.

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: Implanted subjects

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 Composite Score of Change in New York Heart Association (NYHA) Class and Effective Orifice Area (EOA)., measured over baseline and 6 months.

The primary endpoint is a composite score expressed as the percentage of participants analyzed. It combines two criteria: improvement of at least one New York Heart Association (NYHA) class from baseline to 6 months, and an effective orifice area (EOA) of 1.0 cm² or greater at 6 months. The endpoint population is implanted subjects.

NYHA class represents functional status, while EOA is an anatomical measure of the valve opening. Combining them requires success on both dimensions, rather than allowing one component to stand in for the other. This can make the endpoint relevant to a question that asks about functional and anatomical outcomes together. It also means that the composite result alone would not reveal how often each component was met separately; component-specific results are needed to understand which part drove the overall composite.

The registry record identifies the measurement time points and endpoint definition but does not report the primary endpoint result. It also does not report, in the primary endpoint entry, the separate component results or details of how missing component measurements were handled. Therefore, the percentage meeting the composite criterion and the precision of that estimate cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a single-group model, masking as none, and allocation as NA. It lists 20 enrolled participants and an implanted-subject population for the primary endpoint. It does not report a detailed statistical analysis plan, a sample-size justification, interim analyses, or a primary endpoint result. The interpretation should therefore distinguish the design details that are recorded from statistical procedures that are not reported.

What does a single-group design estimate?

General statistical context: a single-group study can describe outcomes among participants who receive the intervention. A proportion meeting an endpoint is a summary of the observed group, not an estimate of the difference between treatment and control. A causal treatment effect generally requires a defensible comparison, and this record does not list a randomized control group. Baseline measurements may help describe change over time, but change from baseline is not itself a randomized comparison and may reflect influences other than the intervention.

The registry's primary endpoint uses baseline and 6-month assessments, but the posted entry gives no numerical outcome. It therefore cannot establish the observed composite proportion, the amount of change, or how precise an estimate would be. It also does not specify in the primary endpoint entry whether analysis was based on all implanted subjects with available measurements or another rule beyond the stated population.

How should the composite endpoint be understood?

General statistical context: a composite endpoint combines multiple criteria into one outcome. Here, a participant must meet both the functional criterion—improvement of at least one NYHA class from baseline to 6 months—and the anatomical criterion—EOA of 1.0 cm² or greater at 6 months. A composite can provide a single summary of joint success, but it can conceal differences between components. Component-level results are useful because they show whether the endpoint reflects both dimensions or is largely determined by one. The registry record describes the definition but does not report the primary composite value or separate component values.

The stated unit is percentage of participants analyzed. General statistical context: a percentage is an estimate based on a numerator and a denominator, and its precision depends in part on the amount of information in that denominator. A confidence interval would communicate uncertainty around a proportion, but the registry record does not report one for this endpoint. No interval should be inferred from the enrollment count because the analyzed denominator and outcome numerator are not reported.

What do the safety counts say?

The registry lists serious adverse event counts for as-treated route groups and for all subjects. Those counts are descriptive. General statistical context: when groups are small, a few participants can have substantial influence on a proportion, and comparisons across groups can be unstable. Here, there is no randomized comparison, and the access-route groups are not identified as equivalent groups differing only in route. The counts therefore should not be treated as estimates of a route effect. The registry record does not provide a statistical comparison or precision interval for these safety counts.

Serious-event terms are listed with percentages, but the entry does not explain their denominator or whether the categories overlap. General statistical context: adverse-event terms can be non-exclusive when one participant experiences multiple types of events. Without the category definitions and denominator, the percentages cannot be added or used to infer the number of unique participants affected by each term.

What do the planning calculations represent?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the stated effect to detect is a fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is total events; for other outcomes, it is participants per arm. These are planning illustrations based on the observed effect, not the trial's own design or a record of observed power. The study itself is described as single-group, so the hypothetical two-arm assumptions do not describe its actual allocation. The registry record does not report the original sample-size justification.

General statistical context: a planning calculation depends on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and analysis method. A calculation cannot repair limitations in the design or substitute for an observed treatment comparison. Nor does a post hoc planning illustration indicate the probability that a study result is true. Since the primary result is not reported in the registry record, no interpretation of a calculated detectable effect as a measure of the study's evidential strength is warranted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 39 outcome measures and one analysis for the primary measure. Secondary outcomes include NYHA classification over time and major adverse cardiovascular and cerebrovascular events (MACCE), with each label repeated in the outcome list. The record does not explain the timing or analytic distinction associated with those repeated labels. It also does not report an approach to multiplicity, such as adjustment of inference across multiple outcomes or time points.

General statistical context: when several outcomes or repeated assessments are examined, the chance of at least one apparently notable finding can increase if each is interpreted separately. A prespecified hierarchy or multiplicity adjustment can help govern interpretation, but the registry record does not report whether such methods were planned or used. The number of listed outcome measures alone does not show that every measure was tested or that any particular adjustment was applied.

The record defines the primary endpoint population as implanted subjects but does not provide the number analyzed for that endpoint, the number meeting the composite criterion, or missing-data handling details. It does not report how incomplete NYHA or EOA measurements were addressed, whether participants with missing follow-up were excluded, or whether any imputation method was used. These omissions limit assessment of how the analyzed population may differ from the enrolled group.

The registry record also does not report an analysis plan, interim analyses, or a sample-size justification. Their absence from the record should not be replaced with assumptions about what investigators may have done. In particular, the enrollment of 20 is not enough to establish the intended precision or power. The planning illustrations are separate from the trial's own design and are not observed power.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac conduction disorders (25.0%), pericardial disorders nec (25.0%), cataract conditions (25.0%), device issues nec (25.0%), cardiac infections (25.0%).

The as-treated safety counts are reported for the Iliofemoral group, the Direct Aortic group, and all subjects. Serious adverse events affected 13 of 16 at risk in the Iliofemoral group, 3 of 4 in the Direct Aortic group, and 16 of 20 among all subjects. For the other adverse-event category, the reported affected counts are 16 of 16, 4 of 4, and 20 of 20, respectively.

These are counts of affected participants as reported in the registry, not event rates adjusted for follow-up time. The record does not state the follow-up duration used for these safety summaries or provide a comparison group. Since the route groups are not described as randomized and the record warns that they are not a like-for-like control comparison, their counts should not be used to rank routes or infer a route-related difference.

The listed serious-event terms each have a reported percentage of 25.0%. The registry entry does not clarify whether the percentages use participants, events, or another denominator, or whether categories overlap. The counts do not establish causation. Deaths are not reported in the listed safety entries; that should not be interpreted as confirmation that no deaths occurred.

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

The registry record describes a study of MDT-2111 TAVI 23 mm in subjects with small aortic annuli and symptomatic severe aortic stenosis deemed difficult for surgical intervention. It specifies a composite primary endpoint that requires both functional improvement and an anatomical threshold at 6 months. It also provides selected as-treated adverse-event counts. These details clarify the intended question and the scope of the posted safety summaries.

The record does not report the numerical primary endpoint result. It therefore does not establish what percentage of implanted subjects met the composite criterion, how the functional and anatomical components behaved separately, or how precisely the outcome was estimated. An absent result is not a null result and should not be read as evidence for or against the intervention.

The single-group design can describe outcomes in the treated population but cannot provide a randomized treatment-versus-control contrast. The Iliofemoral and Direct Aortic categories are access-route groups, not a like-for-like randomized comparison. The adverse-event counts should be read as descriptive observations in those groups. The listed serious-event percentages also lack enough denominator detail in the registry entry to support interpretation as mutually exclusive proportions.

General statistical context: an observed outcome and its uncertainty answer different questions. A point estimate describes the sample, while an interval can express the precision of that estimate under a stated method. Neither an estimate nor a planning calculation resolves the absence of a control group. The registry record does not report a primary endpoint estimate, an interval, or a detailed statistical plan, so conclusions about effect size, precision, or comparative benefit are not supported by these entries.

The study's stated objective is not itself evidence that the objective was achieved. The posted record supports a description of the study design, endpoint definition, and listed safety counts, while leaving the primary outcome result unreported.

13. Why This Trial Matters Statistically

Statistically, this study illustrates the distinction between a defined endpoint and a reported endpoint result. The primary outcome is carefully expressed as a composite of functional status and valve anatomy at a specified follow-up point, but the registry record does not include the percentage meeting that definition. A clear endpoint definition helps readers understand what was intended to be measured; without the result and its denominator, it does not answer how the study participants fared on that measure.

The single-group design also makes the target of inference important. Descriptive outcomes can characterize the treated cohort, but they do not supply the counterfactual comparison needed to estimate how outcomes would differ under another strategy. The two access-route groups should not be mistaken for a control comparison, particularly because the registry record explicitly cautions that they are not like-for-like arms.

The safety entries further demonstrate why denominators and category definitions matter. The all-subject counts are reported alongside route-specific counts, while serious-event terms are reported as percentages without an explanation of their denominator or overlap. Those details are essential for interpreting event summaries and should not be filled in by assumption.

Finally, planning calculations and observed evidence serve different purposes. The record's planning assumptions describe hypothetical two-arm calculations, whereas the trial is listed as single-group. Planning illustrations do not represent observed power and cannot replace the missing primary estimate or a concurrent comparison. Keeping these distinctions explicit prevents design descriptions, safety counts, and hypothetical calculations from being read as stronger evidence than the registry entries support.

14. 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 trial-specific limitations constrain interpretation. First, the registry record describes a single-group study with no randomized comparator. The observed treated-group experience cannot by itself estimate a comparative treatment effect. The access-route subgroups do not resolve this limitation; the record states that they are not a like-for-like control comparison.

Second, the primary endpoint result is not reported in the registry record. The entry defines a composite of NYHA improvement and EOA at 6 months, but gives no result, confidence interval, analyzed denominator, or component-level estimates. The extent of uncertainty around the primary outcome therefore cannot be assessed from the record.

Third, the enrollment is 20, and the route-specific safety groups contain 16 and 4 at risk. These counts describe the listed populations, but the record does not provide uncertainty intervals or a comparative analysis. Small groups can yield imprecise summaries; general statistical context, not a trial-specific estimate.

Fourth, the registry record does not report the statistical analysis plan, sample-size justification, interim analyses, missing-data methods, or multiplicity approach. It is therefore not possible to assess whether the reported analyses followed prespecified rules, how missing 6-month assessments were handled, or how inference across the listed outcomes was managed.

Finally, the serious-event term percentages are not accompanied by a stated denominator or clarification about overlap, and deaths are not reported in the listed safety entries. These gaps limit interpretation of the safety profile. The record's completed status does not fill in the unreported endpoint result or missing analytical details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Clinical Evaluation of MDT-2111 in Subjects With Small Aortic Annuli and Symptomatic Severe Aortic Stenosis — NCT01634269.
• Registry record last updated 2019-10-15; status last verified 2019-10.
• Results first posted 2018-12-17.
• 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.

18. Record Summary

NCT01634269 is a completed, single-group study sponsored by Medtronic Cardiovascular, with an enrollment of 20. It evaluated MDT-2111 TAVI 23 mm in subjects with small aortic annuli and symptomatic severe aortic stenosis deemed difficult for surgical intervention. The primary endpoint combines improvement of at least one NYHA class from baseline to 6 months with an EOA of 1.0 cm² or greater at 6 months.

The registry record does not report the primary endpoint result. Safety counts are listed for Iliofemoral, Direct Aortic, and all subjects as treated, but the route groups are not a like-for-like control comparison. The record does not report a detailed statistical plan, missing-data methods, sample-size justification, or multiplicity approach. Accordingly, the entries support a description of the study and its reported counts, not a randomized comparative conclusion.