Feasibility Study of the Tendyne Mitral Valve System in Mitral Annular Calcification: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Feasibility Study of the Tendyne Mitral Valve System in Mitral Annular Calcification (NCT03539458), a na na study. The primary outcome is Number of Participants With Composite Endpoint of Device Success and Freedom From Device or Procedure Related Serious Adverse Events (SAEs), as Classified by the Clinical Events Committee (CEC).

2. Clinical Question

3. Trial Design

This was a prospective, single-arm, multi-center feasibility clinical study of the Tendyne Mitral Valve System. Its stated purpose was to examine use of the device in eligible participants with symptomatic, severe mitral regurgitation and severe mitral annular calcification. The listed intervention was implantation of the Tendyne Mitral Valve System, and the sole arm description states that participants underwent a procedure with that system.

The registry lists enrollment of 11 and records the study as completed. The recorded start date is 2018-10-10, and the primary completion date is 2019-11-29. Phase is listed as NA. Allocation is also listed as NA, while masking is listed as none. These design details are consistent with an open-label, single-group feasibility study, not a randomized comparison.

For the primary endpoint, the registry states that the analyzed population includes all subjects registered and implanted in the study. It sets the assessment timeframe at 30 days post implant. The record does not report the observed endpoint count, an effect estimate, a confidence interval, or a primary endpoint analysis. Although the study is marked completed, that status does not itself supply the missing result.

A single-arm design can describe what was observed among participants receiving the device, including endpoint and safety outcomes when reported. Without a concurrent comparison group, those observations cannot isolate the device’s effect from other influences or establish how outcomes compare with an alternative. The registry explicitly cautions that its arms are not a like-for-like control comparison; in this study there is only one listed arm.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number of participants analyzed includes all subjects that were registered and implanted in the study.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Composite Endpoint of Device Success and Freedom From Device or Procedure Related Serious Adverse Events (SAEs), as Classified by the Clinical Events Committee (CEC), measured over 30 days post implant.

The primary endpoint counts participants meeting a composite of device success and freedom from device- or procedure-related serious adverse events. An independent Clinical Events Committee classified the relevant adverse events. The assessment timeframe was 30 days post implant.

Device success required all listed conditions. These included absence of procedural mortality or stroke; proper placement and positioning; freedom from unplanned surgical or interventional procedures related to the device or access procedure; and continued intended safety and performance. The latter requirement covered no evidence of structural or functional failure, no specified device-related technical failure issues or complications, and reduction of mitral regurgitation to optimal or acceptable levels without significant structural valve dysfunction and with no greater than mild (1+) paravalvular mitral regurgitation without associated hemolysis.

A composite can capture several clinically relevant aspects of an intervention in one endpoint, but its interpretation depends on the definition and on which components participants meet. Requiring every device-success condition makes the success classification conjunctive: failure to satisfy a required component means the full device-success definition is not met. Freedom from related serious adverse events is an additional part of the composite. The registry defines these criteria, but the participant count meeting the combined endpoint is not reported in the registry record. The endpoint’s observed frequency and precision therefore cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends first on identifying what was counted, in whom, and over what period. This record defines its primary outcome as a participant count, not a mean or a time-to-event estimate. The target population for that count is described as participants registered and implanted. Its timeframe is 30 days post implant. These definitions clarify the intended measurement, but the recorded endpoint count is not reported in the registry record.

What does a participant count tell the reader?

A count reports how many participants satisfy a specified outcome definition. For a binary outcome, each participant is classified as meeting or not meeting the definition. The endpoint is more elaborate than a single event: it combines device success criteria with freedom from device- or procedure-related serious adverse events. The registry does not report the participant-level classifications or the final count. It is therefore not possible to describe the observed frequency, calculate an uncertainty interval, or assess which components most often determined the composite result.

In general, an estimate of an event frequency is more informative when accompanied by a confidence interval. A confidence interval expresses the statistical uncertainty associated with an estimate under the method used; it does not guarantee that the true value lies within the interval, and it does not account automatically for design limitations or biased measurement. No confidence interval for this primary outcome is reported in the registry record. No unadjusted or adjusted primary analysis is listed either.

Why does the single-group design matter?

A single-group study records outcomes among participants who received the intervention. It can describe feasibility and observed outcomes in the enrolled population. It does not, by itself, establish what would have happened to those same participants under another intervention or without the device. That missing counterfactual is why a single-group result cannot be interpreted as a comparative treatment effect. This study has one listed device arm, and the registry expressly identifies the design as not a randomized comparison.

Masking is listed as none. In general, lack of masking can matter when outcomes involve judgment, reporting, or decisions about whether criteria have been met. Here, the registry says that all device- or procedure-related adverse events are adjudicated by an independent Clinical Events Committee. Independent adjudication describes an oversight process for event classification; it does not turn the single-group design into a controlled comparison, and it does not supply unreported endpoint results.

How should safety counts be read?

The registry reports participants at risk and affected for serious and other adverse events. These are descriptive counts within the device arm. A count of participants affected is not necessarily a count of event episodes: an affected participant could have more than one event. Likewise, terms and percentages listed for serious events need not represent mutually exclusive sets. In general, event rates and comparisons require clear definitions of the numerator, denominator, observation period, and event handling. The listed at-risk counts provide a denominator for the displayed arm summaries, but the record does not provide all details needed to reconstruct event-level analyses.

Over-dispersion is a general concern when event counts vary more than a simple statistical model expects, for example when some participants experience multiple events. That can make standard uncertainty estimates too narrow if the model assumes independent, equally variable observations. The registry’s primary outcome is a count of participants meeting a binary composite, rather than a repeated-event count, and no model specification or analysis is listed. It is therefore not appropriate to claim that an over-dispersion adjustment was used or required for the primary endpoint. Event-level modeling details are not reported in the registry record.

What do planning calculations mean?

Sample-size calculations are prospective planning tools: they describe how many participants a future study might need under specified assumptions about the effect to detect, the significance level, allocation, and statistical model. They are not evidence that an effect was observed with a particular degree of certainty. The general planning description associated with this record refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also states that the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, that description refers to total events, while other outcomes are expressed as participants per arm.

Those assumptions do not describe this study’s design, which has a single group and no like-for-like comparator. A two-arm planning scenario cannot be read as an observed comparison in this trial. The registry record does not provide the primary endpoint estimate needed to assess a planning illustration based on the observed effect, nor does it report a study-specific sample-size justification. Such planning assumptions must not be mistaken for observed power or for a result of the feasibility study.

Finally, the registry lists zero analyses. This means the record does not identify a formal statistical analysis for the outcome. It does not establish whether any analyses were conducted outside the registry record. The method, handling of missing outcome data, confidence-interval approach, and any adjustment for covariates are not reported in the registry record. Interpretation should therefore remain tied to the endpoint definitions and descriptive entries that are actually recorded.

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("Device Arm")
n      <- c(11)
events <- c(7)
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  Device Arm  11  7  63.6  30.8  89.1  35.4  84.8  34.9  84.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. The primary endpoint is a composite with several required device-success components and a freedom-from-serious-adverse-events condition. The record does not report how many components were assessed separately as additional outcomes, whether secondary or exploratory hypotheses were tested, or whether any multiplicity adjustment was planned or applied. Multiplicity matters in general when many outcomes or comparisons are examined, because repeated testing can increase the chance of a nominally notable finding. There is not enough information in the registry record to assess that issue for any unlisted analyses.

The primary-endpoint population is described as all subjects registered and implanted. The registry does not report the number of participants included in the endpoint analysis, the amount or pattern of missing outcome data, or how missing assessments were handled. It also does not state whether any participants were excluded after implantation or whether endpoint components were unavailable for some participants. The enrolled count and adverse-event denominators do not resolve these questions about the endpoint analysis population.

In general, missing data can affect an estimate if outcome availability is related to participants’ health, treatment experience, or endpoint status. Analysis choices such as treating missing outcomes as failures, excluding incomplete cases, or using imputation can lead to different interpretations. None of those approaches is identified in the registry record, so no such approach should be attributed to this study.

The registry does specify that the primary-endpoint population includes registered and implanted subjects and that adverse events are adjudicated by an independent Clinical Events Committee. It does not report a statistical analysis plan, a prespecified missing-data procedure, or the treatment of withdrawals. These details are not reported in the registry record. Consequently, the endpoint’s analysis population and robustness to incomplete information cannot be evaluated from the record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bleeding (18.2%), hemolysis (9.1%), paravalvular leak (9.1%), arrhythmia or conduction disturbance (9.1%), worsening congestive heart failure (9.1%).

The device arm lists 11 participants at risk for serious adverse events, with 5 affected. For other adverse events, 11 are listed at risk and 7 affected. The record also lists 1 death. These figures describe the study arm; they are not comparative estimates, because there is no control arm. The registry does not specify in the summary whether the listed death was related to the device or procedure.

The most common listed serious-event term is Bleeding at 18.2%. Hemolysis, Paravalvular Leak, Arrhythmia or conduction disturbance, Worsening Congestive Heart Failure, and Mesenteric Ischemia and Hemorrhagic Shock are each listed at 9.1%. These percentages are registry entries. They should not be added: a participant may be represented under more than one event term, and the record does not state that terms are mutually exclusive. The terms also do not alone explain duration, severity grading, timing, or causal attribution beyond what is explicitly stated.

Serious adverse events were adjudicated by an independent Clinical Events Committee for the primary endpoint definition. The summary does not give event-level narratives or distinguish every event’s relationship to device or procedure. These safety observations should therefore be read descriptively and within the study’s feasibility setting, rather than as a comparative estimate or a complete accounting of clinical risk.

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

The record establishes that a prospective, single-arm feasibility study of the Tendyne Mitral Valve System was conducted in participants with symptomatic, severe mitral regurgitation and severe mitral annular calcification. It defines a demanding primary composite for 30 days post implant and describes the conditions required for device success. It also reports descriptive safety entries for the device arm, including participants affected by serious and other adverse events, listed serious-event terms, and a death count.

It does not report the number of participants who met the primary composite, a confidence interval, or an analysis of the endpoint. As a result, the primary endpoint’s observed frequency and precision cannot be interpreted from this registry record. A completed study status does not supply a missing outcome estimate. The available safety information likewise does not provide a comparison with another treatment or a no-device group.

Because the study has one group and no randomized comparator, outcomes cannot be attributed to the device by comparison with an alternative. The observations may describe what occurred among enrolled participants, but they cannot establish a causal treatment effect. Nor can percentages for individual adverse-event terms be interpreted as unique participant groups or combined into a total, since overlap is not ruled out.

The record is consequently informative about the intended feasibility question, endpoint construction, and some recorded safety summaries, but limited for judging the primary outcome. It does not report enough information to evaluate missing primary-endpoint data, the analysis method, or statistical uncertainty. Any interpretation should distinguish the protocol-defined endpoint from an observed endpoint result, which is not reported in the registry record.

14. Why This Trial Matters Statistically

Feasibility studies often address whether an intervention can be undertaken in a selected clinical setting and document outcomes that may inform later evaluation. Statistically, it is important to separate that descriptive purpose from a comparative effectiveness question. This study’s single-group structure can describe recorded experience with device implantation, but it has no concurrent control arm to estimate how outcomes differ under another strategy.

The primary endpoint also illustrates how composite outcomes combine several dimensions. Device success includes procedural, positioning, intervention, performance, and valve-function conditions, while the full endpoint additionally requires freedom from related serious adverse events. A composite can provide a broad summary, but the meaning of the overall result depends on its exact definition and the contribution of its components. The registry defines those criteria but does not report the number meeting the composite, so the result cannot be interpreted component by component or as a complete endpoint frequency.

The safety summaries show why denominators and event definitions matter. Participant counts affected by serious and other events are distinct summary categories, while serious-event terms and percentages may overlap. Without event-level details or a comparator, the entries support description rather than a comparative risk estimate.

For biostatistical interpretation, the record highlights a basic principle: a study’s design, endpoint specification, and reported analysis jointly determine what can be concluded. A completed feasibility study can contribute useful descriptive information, but absent primary results, uncertainty estimates, and a comparison group, it cannot answer a treatment-effect question. Transparent reporting of participant flow, endpoint counts, missing-data handling, analysis methods, and event details would be necessary for a fuller assessment.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation of this registry record is that it defines the primary endpoint without reporting its observed participant count. No primary effect estimate, confidence interval, or analysis result is listed. Therefore, the stated primary question cannot be answered from the record. The fact that the study is marked completed does not resolve this reporting gap.

The single-group design is another important limitation for interpretation. Outcomes in the device arm cannot be contrasted with outcomes under another treatment or no device, and the record explicitly says the arms are not a like-for-like control comparison. The findings are therefore descriptive rather than comparative. The study is described as a feasibility investigation, not as a randomized trial.

The registry reports enrollment of 11, but does not give a participant flow account, the number included in the primary endpoint analysis, or the handling of missing or unavailable endpoint data. It does not report a statistical analysis plan, the method used to estimate uncertainty, or whether covariates were considered. The registry lists zero analyses, so details of any formal analysis are not available in the record.

Safety summaries provide affected-participant counts and serious-event terms, but do not include event-level narratives, timing, duration, severity grading beyond the serious classification, or complete causal attribution. The listed death count is not further characterized in the summary. Serious-event term percentages may overlap, and the record does not establish that they identify distinct participants.

The eligibility criteria and participant characteristics are not fully detailed in the record. Generalizability beyond the selected study population cannot be assessed from these registry entries. Finally, no study-specific sample-size justification or interim-analysis plan is reported in the registry record. These omissions limit assessment of design rationale and statistical precision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Feasibility Study of the Tendyne Mitral Valve System in Mitral Annular Calcification — NCT03539458.
• Registry record last updated 2024-11-18; status last verified 2024-10.
• Results first posted 2021-01-26.
• 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 describes NCT03539458, a completed, prospective, single-arm, multi-center feasibility study of the Tendyne Mitral Valve System in eligible participants with symptomatic, severe mitral regurgitation and severe mitral annular calcification. Enrollment is listed as 11. The recorded study start date is 2018-10-10, and primary completion is recorded as 2019-11-29. Phase and allocation are listed as NA, and masking is listed as none.

The primary endpoint was a participant count for a composite of device success and freedom from device- or procedure-related serious adverse events, assessed 30 days post implant and classified by an independent Clinical Events Committee. The endpoint definition is recorded, but its participant count and analysis are not reported in the registry record.

For the device arm, the record lists 11 at risk and 5 affected for serious adverse events, 11 at risk and 7 affected for other adverse events, and 1 death. Serious-event terms and percentages are also listed. There is no randomized comparator, and the registry lists zero analyses.