Mitral Implantation of TRAnscatheter vaLves: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mitral Implantation of TRAnscatheter vaLves (NCT02370511), a non-randomized na study. The primary outcome is Technical Success at Exit From the Cath Lab..

2. Clinical Question

The trial asks whether transcatheter mitral valve replacement can be performed with technical success in patients with severe symptomatic mitral valve disease who face challenging surgical circumstances. It covers three distinct clinical settings: severe calcific native mitral valve disease with severe mitral annular calcification (MAC), a failing surgical mitral ring, and a failing surgical bioprosthesis. The registry describes the native-valve group as having extremely high surgical risk; the ring and bioprosthesis groups had symptomatic failure resulting in severe mitral regurgitation or stenosis.

The intervention was transcatheter mitral valve replacement. The official title identifies the SAPIEN XT and SAPIEN 3 transcatheter heart valves and their delivery systems. The record frames the study purpose as establishing safety and feasibility, rather than comparing the device with a randomized control treatment. The principal question is whether participants could meet the registry’s definition of technical success at exit from the catheterization laboratory. The endpoint includes successful delivery and retrieval, deployment of a single valve in the correct position, adequate prosthesis performance, no need for additional surgery or re-intervention, and leaving the catheterization laboratory alive.

The record also lists procedural success as a secondary outcome and reports serious adverse-event counts and deaths for each clinical group. It does not report the primary technical-success result, so the central question cannot be answered from the posted results. The groups represent different clinical settings, not interchangeable treatment and control populations.

3. Trial Design

This was a completed, non-randomized, single-group device study with no masking. The registry lists 91 participants as enrolled. The study began on 2015-02-25, and primary completion was recorded as 2018-12. The registry lists the phase as not applicable and the condition as mitral valve disease.

Participants were categorized according to their mitral-valve setting: native mitral valve with severe MAC, valve-in-ring, or valve-in-valve. The first group had symptomatic severe calcific native mitral valve disease and extremely high surgical risk. The other groups had symptomatic failing surgical rings or bioprostheses, respectively, resulting in severe mitral regurgitation or stenosis. Each group received transcatheter mitral valve replacement.

Because allocation was non-randomized and the model was single-group, these groups are not randomized arms in a comparative trial. Their underlying conditions and prior valve procedures differ, so contrasts between their outcomes would not isolate a treatment effect. The record does not describe a concurrent control group or a masking procedure.

The primary outcome was technical success at exit from the catheterization laboratory, with a stated timeframe of 30 days. Procedural success was listed as a secondary outcome. The registry record lists four outcome measures, but does not report the primary endpoint result or details of the other outcome results in the information available for interpretation. The protocol’s sample-size justification and the detailed statistical analysis plan 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.

Overall Study

Reasons for not completing this period:

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 Technical Success at Exit From the Cath Lab., measured over 30 days.

The primary endpoint counts participants who achieved technical success at exit from the catheterization laboratory. The definition combines several procedural conditions: successful vascular delivery and retrieval of the valve delivery system, deployment of a single valve, correct valve position, adequate prosthesis performance, no need for additional surgery or re-intervention, and survival until leaving the catheterization laboratory.

A composite definition of this kind treats success as requiring all specified conditions, rather than capturing only one technical step. In this trial, adequate performance is defined as mitral valve area (MVA) > 1.5 cm2 without residual mitral regurgitation (MR) grade ≥2 (+). The endpoint therefore combines device delivery and positioning with an immediate measure of valve performance and the need for further intervention.

Technical success is used to assess whether a complex device procedure reached its specified procedural goals. It is distinct from a longer-term clinical outcome: the registry’s definition focuses on events through exit from the catheterization laboratory, although its stated timeframe is 30 days. The record does not clarify how that timeframe relates to the point-of-procedure definition.

The primary endpoint’s result is not reported in the registry record. Consequently, the count of participants meeting the definition, and the precision of that estimate, cannot be described from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the study as non-randomized and single-group. These design features determine what statistical conclusions are reasonable. Random allocation helps balance known and unknown prognostic factors across comparison groups, on average. Since allocation was not randomized, the three clinical groups should be understood as distinct cohorts defined by valve condition and prior procedure, not as treatment and control arms. Differences in their observed counts could reflect differences in the participants and clinical settings as well as any procedural factors.

What does a participant count represent?

The primary outcome is a count of participants who meet a binary definition: each participant either meets all stated technical-success criteria or does not. A count is directly interpretable as the number of participants with the defined outcome. To assess how frequent that outcome was, a denominator and an analysis population are also needed. The registry supplies the overall enrollment and adverse-event group sizes, but it does not report the primary endpoint count or its analysis denominator. A rate or uncertainty interval for the primary endpoint therefore cannot be interpreted from the posted record.

A confidence interval, as a general statistical concept, describes uncertainty around an estimated quantity under specified assumptions. It does not guarantee that the true value lies within the interval, and it does not correct for bias caused by non-randomized group selection. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be assessed from the listed primary outcome information.

Why distinguish the groups?

The native mitral valve with severe MAC, valve-in-ring, and valve-in-valve categories reflect different disease and procedural contexts. A pooled result across these categories, if reported, would summarize a mixture of clinical settings. A group-specific result would describe its own cohort. Neither form alone establishes how the device compares with another treatment. The registry’s non-randomized allocation means that between-group comparisons are potentially confounded: participant characteristics related to both group membership and outcome may explain some or all of an observed difference.

For the same reason, an unadjusted contrast is descriptive rather than a causal estimate. Statistical adjustment can sometimes address measured differences, but it cannot automatically eliminate differences that were not measured or were inadequately modeled. The registry lists no analyses, and an adjusted analysis plan is not reported in the registry record.

How should adverse-event counts be read?

The record gives counts of participants at risk and counts affected for serious adverse events and other adverse events, plus deaths, in each clinical group. Such summaries should be read with attention to the event definition, observation period, and denominator. Those details matter because adverse events may be counted as participants with at least one event or as total event episodes, and those are not the same quantity. The record’s outcome interpretation identifies event counts as participants with an event, but detailed event ascertainment and follow-up rules are not reported in the registry record.

The listed serious-event terms include percentages, but their denominator and group scope are not stated. Without that information, the percentages cannot be treated as group-specific estimates or used to compare the three cohorts. A descriptive list of terms also does not show uncertainty around each percentage.

What do planning assumptions mean?

The record describes sample-size planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. These are planning illustrations, not observed power and not evidence that the trial was designed or powered according to those assumptions. The illustrations do not replace a protocol-based sample-size justification. That justification is not reported in the registry record.

In general, planning calculations estimate the sample size needed to detect an effect under stated assumptions. Their interpretation depends on the endpoint, effect size, variability, allocation, and statistical model. A calculation based on an observed effect can be especially sensitive to how that effect was estimated. The posted primary technical-success result is absent, so the primary outcome cannot be connected to a reported effect estimate in the registry information available for interpretation.

What can be concluded from the analysis record?

The registry lists zero analyses. It therefore does not provide an inferential analysis, such as a reported hypothesis test or adjusted model, for interpreting the outcomes. That absence does not show that no analyses were conducted outside the registry; it means those analyses are not reported in the registry record. Statistical significance, effect estimates, and their precision should not be inferred from descriptive counts alone.

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("Native Mitral Valve With Severe MAC", "Valve-in-Ring", "Valve-in-Valve")
n      <- c(31, 30, 30)
events <- c(23, 20, 30)
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  Native Mitral Valve With Severe MAC  31  23  74.2  55.4  88.1  56.8  86.3  56.6  86.3
ARM  Valve-in-Ring  30  20  66.7  47.2  82.7  48.8  80.8  48.6  80.8
ARM  Valve-in-Valve  30  30  100.0  88.4  100.0  88.6  100.0  88.8  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and identifies technical success at exit from the catheterization laboratory as the primary outcome. Procedural success is listed as a secondary outcome. The other outcome measures and their results are not described in the available record. The registry also lists zero analyses, so it does not report hypothesis tests or a strategy for handling multiple outcomes.

Multiplicity arises when several outcomes or statistical tests are assessed: the chance of at least one apparently notable finding can increase as more tests are conducted. Statistical plans may address this by identifying a primary endpoint and specifying how secondary outcomes will be interpreted. The record identifies a primary endpoint, but multiplicity procedures and the planned hierarchy of other outcomes are not reported in the registry record. It would be inappropriate to assume that an adjustment was or was not made outside the registry.

The primary endpoint result is not reported, and the registry record does not describe missing outcome data, exclusions, or the analysis population for that endpoint. It also does not state how participants with incomplete endpoint information were handled. Missing-data methods can affect both the estimate and its uncertainty; no particular method can be attributed to this study from the available record.

Likewise, the record does not describe whether analyses followed an intention-to-treat, per-protocol, or other population definition. These terms refer to different rules for deciding which participants contribute to an analysis, so the denominator matters when interpreting a participant count. The posted adverse-event group sizes do not establish the analysis population used for the primary endpoint.

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: new rehospitalization for heart failure (35.5%), acute kidney injury (16.1%), atrial fibrillation (16.1%), hemolytic anemia (16.1%), new permanent pacemaker requirement (16.1%).

The adverse-event information is presented as participant counts within three clinical groups. For serious adverse events, the record lists 18 affected participants among 31 at risk in the native mitral valve with severe MAC group, 13 among 30 in the valve-in-ring group, and 8 among 30 in the valve-in-valve group. The counts listed for other adverse events are 17 among 31, 12 among 30, and 6 among 30, respectively. The death counts are 10, 7, and 1, respectively.

These are descriptive counts, not randomized comparisons. The groups differ by valve setting, and the registry does not report an analysis that adjusts for group differences. The counts alone do not identify the cause of an event or establish that the procedure caused it. The registry record also does not give the observation period and detailed ascertainment rules for these event summaries.

The listed serious-event terms include rehospitalization for heart failure at 35.5%, acute kidney injury, atrial fibrillation, hemolytic anemia, and new permanent pacemaker requirement each at 16.1%, and mitral valve reintervention after the index procedure at 12.9%. The denominator and population for these percentages are not reported in the registry record, so they should not be read as rates for a particular group.

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

The registry record documents a completed study of transcatheter mitral valve replacement in participants with severe mitral valve disease across native-valve, valve-in-ring, and valve-in-valve settings. It reports serious adverse-event counts, other adverse-event counts, deaths, and a list of serious-event terms. These data describe the reported participants and groups, subject to the event definitions and follow-up information available in the registry.

The record does not report the primary technical-success count or estimate. Therefore, it cannot establish from the posted results how often the stated technical-success criteria were met, or the precision of such an estimate. The registry’s stated purpose of assessing safety and feasibility is not itself a result. Nor does the presence of an endpoint definition demonstrate that the endpoint was achieved.

The trial was non-randomized and single-group, with clinical groups that represent different valve conditions and prior procedures. Their outcomes cannot be treated as a like-for-like comparison of treatment strategies. A difference between the groups would not, on its own, identify a causal effect of the device, and no inferential analysis is listed.

The event counts also need context about follow-up, event definitions, and analysis populations. Those details, along with missing-data handling and the primary endpoint result, are not reported in the registry record. The study therefore offers descriptive safety information, but the available record does not support a conclusion about comparative benefit or a complete statistical assessment of technical success.

14. Why This Trial Matters Statistically

This trial is statistically important because it illustrates how a device study can address a technically complex intervention in several clinical settings while leaving important limits on comparison. The three groups involve native mitral valve disease with severe MAC, failing surgical rings, and failing surgical bioprostheses. Those categories are clinically distinct, and their outcomes should not be combined or contrasted as though participants had been randomly assigned to otherwise comparable arms.

The primary endpoint is a composite procedural measure. Its criteria cover delivery and retrieval, deployment, position, valve performance, need for further intervention, and survival until leaving the catheterization laboratory. Such an endpoint can summarize whether multiple procedural goals were achieved, but interpretation depends on the definition and on a reported result. The registry supplies the definition but not the primary outcome count.

The safety summaries also show why denominators and event definitions matter. Participant counts are reported for serious and other adverse events, and percentages are listed for selected serious-event terms, but the percentage denominator is not stated. Without that context, the figures cannot be read as directly comparable rates across the groups.

More broadly, a completed registry record does not necessarily contain the analysis needed to answer every statistical question. Here, the record lists zero analyses and does not report the primary endpoint result, missing-data handling, or analysis populations. Recognizing these gaps helps distinguish what the record describes from what would require additional results or a prespecified statistical analysis.

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 consequential limitation for interpreting the primary question is that the registry record does not report the primary technical-success result. Although the endpoint definition and timeframe are stated, there is no reported count or estimate for participants meeting it. The endpoint’s precision therefore cannot be assessed.

The study is non-randomized and single-group. Its three clinical categories are not like-for-like control groups: they represent different valve conditions and prior surgical procedures. Any cross-group contrast would be vulnerable to differences in participant characteristics and clinical context. The registry lists no analyses that could support an adjusted comparison.

The adverse-event summaries lack important interpretive details in the record, including the observation period and detailed ascertainment rules. The denominator for percentages attached to serious-event terms is not reported. The record also does not specify missing-data handling, exclusions, or the analysis population for the primary endpoint.

Four outcome measures are listed, but the available information does not describe all of them or report their results. The registry lists zero analyses; multiplicity procedures and a detailed statistical plan are not reported in the registry record. The protocol’s sample-size justification is also not reported in the registry record. These omissions limit assessment of outcome selection, precision, and the relationship between planned and reported analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Mitral Implantation of TRAnscatheter vaLves — NCT02370511.
• Registry record last updated 2023-10-10; status last verified 2023-10.
• Results first posted 2021-08-16.
• 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

NCT02370511, titled “Mitral Implantation of TRAnscatheter vaLves,” is a completed, non-randomized, single-group study of transcatheter mitral valve replacement. The registry lists 91 participants enrolled and three clinical groups: native mitral valve with severe MAC, valve-in-ring, and valve-in-valve.

The primary outcome is technical success at exit from the catheterization laboratory, with a stated timeframe of 30 days. Procedural success is listed as a secondary outcome. Serious and other adverse-event counts and deaths are reported by group, along with selected serious-event terms.

The primary technical-success result is not reported in the registry record. The registry lists zero analyses, and does not report the analysis population, missing-data methods, multiplicity approach, or detailed statistical plan. The available results are descriptive and do not constitute a randomized comparison between the clinical groups.