NHLBI DIR Transcatheter Mitral Cerclage Annuloplasty Early Feasibility Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NHLBI DIR Transcatheter Mitral Cerclage Annuloplasty Early Feasibility Study (NCT03929913), a na na study. The primary outcome is The Primary Endpoint is Technical Success.

2. Clinical Question

3. Trial Design

NCT03929913 is an early feasibility study of transcatheter mitral cerclage annuloplasty. The registry lists the study as completed, with an enrollment of 19 participants. The recorded start date is 2019-05-07 and the primary completion date is 2021-02-23. The listed phase and allocation are NA, and masking is none. The design is single-group, so the registry record does not describe a concurrent control arm or randomized allocation.

The intervention is the Transmural Systems Transcatheter Mitral Cerclage Annuloplasty device. The study evaluates feasibility and safety in symptomatic heart failure accompanied by mitral valve regurgitation despite optimal medical therapy, as described in the arm description. The registry's summary explains that TMCA is a catheter procedure and describes its intended purse-string compression of the mitral valve. The protocol was changed to include people with regurgitation despite prior Mitra-Clip treatment and people with symptomatic heart failure with mild regurgitation. Other details of the eligibility criteria, enrollment process, participating sites, and participant characteristics are not reported in the registry record.

The primary endpoint is technical success, measured at exit from the catheterization laboratory. Procedural success is identified as a secondary endpoint. The record lists two outcome measures, but does not report outcome results for either endpoint. No statistical analysis is recorded. The registry record also does not report the study's sample-size justification, planned stopping rules, interim analyses, or a detailed statistical plan. Since there is no separate comparison group, the design is suited to describing observations in the treated group, not to estimating a randomized contrast between interventions.

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 The Primary Endpoint is Technical Success, measured over 1 minute following procedure discharge (Exit from the catheterization laboratory).

The primary endpoint is technical success at the specified procedural time point: one minute following procedure discharge, defined as exit from the catheterization laboratory. It is a binary participant-level outcome: each participant either meets the full definition or does not. The criteria are conjunctive, meaning that all must be present for success. They include being alive; successful deployment and correct positioning of a single intended TMCA; retrieval of the delivery system; absence of TMCA-related coronary artery compression and of an additional procedure such as PCI to relieve such compression; and no additional unplanned or emergency surgery or re-intervention related to the device or delivery system. Repositioning and recapture, if needed, are explicitly not classified as failure.

A procedural endpoint is useful in an early feasibility study because it records whether the intended device procedure can be completed under prespecified conditions at the procedural time point. The combined definition captures several distinct aspects of the procedure rather than device placement alone. That breadth also matters for interpretation: a participant must satisfy every component, and a single unmet component prevents classification as technical success. The endpoint does not, by itself, describe longer-term outcomes or establish comparative benefit. Although the registry states the endpoint definition and timeframe, the number of participants meeting it is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study with a binary primary outcome. The outcome is whether each participant meets the complete technical-success definition. A binary endpoint is often summarized as a count of participants meeting the definition and a count not meeting it; an uncertainty interval can also be used to convey how much the observed estimate may vary because of sampling. These are general statistical concepts. The registry record does not provide a primary endpoint count, an estimate, or an interval, so those quantities cannot be interpreted for this study.

What does a binary endpoint capture?

For a participant-level binary outcome, classification depends on the stated criteria and assessment time. Here, technical success is not simply whether a device was deployed. It requires all the specified conditions at the procedural assessment. The rule that repositioning and recapture are not classified as failure is part of the endpoint definition and affects how such a procedure is categorized. When a composite endpoint combines multiple conditions, its overall frequency reflects the combined rule. Component-level results can help explain which criteria were or were not met, but those results are not reported in the registry record.

As a general matter, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the method used. It is not a range containing a known fixed share of individual outcomes, and it does not measure bias or account automatically for limitations in study design. In a single-group study, an interval around a success frequency would describe uncertainty about that group's outcome frequency, not uncertainty about a randomized treatment contrast. No such interval is reported for the primary endpoint.

Why does the design affect the statistical question?

In a randomized comparison, the difference between groups can be used to estimate a contrast under the trial's design and analysis assumptions. This study has no separate comparator group: allocation is recorded as NA and the design is single-group. Its endpoint can therefore be described as an outcome among participants receiving TMCA, but there is no internal randomized estimate of what would have occurred under a different intervention. General statistical adjustment cannot create the missing concurrent control group or turn a single-group observation into a randomized comparison.

Early feasibility research commonly focuses on whether a procedure and its devices can be used as intended and on recording safety observations. That is general context, not a claim about an unreported analysis plan. The registry explicitly labels this study an early feasibility study and identifies feasibility and safety in the arm description. The specific statistical objectives beyond the registered endpoint definitions are not reported in the registry record.

What can event counts tell the reader?

Event counts give a direct description of how many participants in the listed group were affected according to the registry's categories. They do not show event timing, duration, recurrence, severity beyond the serious-event classification, or causal relationship unless those details are separately reported. Several events can occur in one participant, and a participant can appear in more than one event category. Thus, counts across different adverse-event terms should not be added or treated as mutually exclusive unless the record establishes that they are. That additional information is not reported in the registry record.

Over-dispersion is a general concern when event-count methods assume that counts vary in a prescribed way but actual variability is greater. It is more relevant to analyses of repeated events or counts than to a simple participant-level yes-or-no endpoint. The registry reports participant counts for adverse-event categories in the registry record, but does not give an event-level analysis or statistical model. There is no basis to claim that a particular count model, adjustment, or over-dispersion correction was used.

What can planning calculations establish?

Sample-size calculations are planning tools: they describe how many participants might be needed under specified assumptions to detect a chosen effect with a chosen statistical procedure. They depend on the assumed effect, outcome variability, significance threshold, allocation, and analysis method. These are general principles. The registry record does not report a trial-specific sample-size justification or planned effect size, so no claim about the original planning rationale is warranted. Planning illustrations based on an observed effect, when available, are not the study's observed power and do not prove that the trial was adequately or inadequately planned. The posted record does not report a primary endpoint result from which such an observed effect could be interpreted.

The registry records no statistical analyses for the outcomes. The specific estimator, confidence-interval method, handling of protocol deviations, analysis population, and approach to missing observations are not reported in the registry record. Without those details and without the endpoint results, the reader should distinguish the prespecified endpoint definition from any statistical analysis that may have occurred outside the registry entry. No analysis method should be attributed to the study without a record of it.

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("Transcatheter Mitral Valve Cerclage Annuloplasty")
n      <- c(19)
events <- c(17)
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  Transcatheter Mitral Valve Cerclage Annuloplasty  19  17  89.5  66.9  98.7  68.6  97.1  68.3  96.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary technical-success endpoint and a secondary procedural-success endpoint. When a study tests multiple outcomes, multiplicity can arise because the chance of at least one apparently notable result may increase as more hypotheses are tested. General methods for addressing multiplicity include prespecifying a hierarchy, adjusting statistical thresholds, or clearly treating secondary analyses as descriptive. The registry record does not report whether any multiplicity strategy was planned or used, nor does it provide outcome analyses or p-values to which such a strategy could be applied.

Missing-data handling is also not reported in the registry record. The endpoint definition specifies what constitutes technical success, but does not state how an unavailable assessment, incomplete procedure record, or other missing endpoint information would be classified. The reported enrollment is 19 participants; the record does not specify whether all enrolled participants were included in each endpoint analysis or whether any were excluded.

The analysis populations are not reported in the registry record. For example, the record does not identify an intention-to-treat, per-protocol, or other named population for endpoint analysis. No inference should be made that a particular population or missing-data rule was used. These omissions matter because endpoint estimates can depend on who is included and how unobserved outcomes are handled. With no primary or secondary outcome result reported, the impact of any missing data or multiplicity procedure cannot be assessed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: heart failure (36.8%), atrioventricular block complete (21.1%), hypotension (15.8%), acute kidney injury (10.5%), atrial fibrillation (10.5%).

For the Transcatheter Mitral Valve Cerclage Annuloplasty group, the registry reports 12 participants with serious adverse events among 19 at risk, and 19 participants with other adverse events among 19 at risk. It also records 5 deaths. These counts should be read as distinct registry summaries, not as a complete account of when events occurred or why they occurred. The registry entries do not establish that every event or death was caused by the device or procedure, and the relationship assessment is not reported in the registry record.

The serious-event terms listed include Heart failure at 36.8%, Atrioventricular block complete at 21.1%, Hypotension at 15.8%, Acute kidney injury at 10.5%, Atrial fibrillation at 10.5%, and Encephalopathy at 10.5%. The denominator used for these term percentages is not reported in the registry record. Terms may overlap within participants; the counts or percentages for different terms should not be added to produce a total number of affected participants. The registry summary does not give timing, recurrence, or participant-level overlap for these terms. These safety figures describe what was recorded in this group and cannot provide a comparative estimate against an untreated or alternative-treatment group.

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

The registry entry identifies an early feasibility evaluation of TMCA in a single group of 19 participants. It defines a primary technical-success endpoint and a secondary procedural-success endpoint, and it records adverse-event summaries. The primary endpoint's detailed definition is useful for understanding what the study intended to count as technical success: the endpoint encompasses survival to the specified procedural assessment, device deployment and position, retrieval of the delivery system, absence of specified coronary complications or corrective intervention, and absence of specified unplanned surgery or re-intervention.

However, the registry record does not report the number of participants who met technical success or procedural success. It therefore does not establish the observed frequency of either outcome. A completed study status and a clear endpoint definition are not substitutes for outcome results. The record also does not report a statistical analysis or a comparison group. No comparative effectiveness conclusion can be drawn from this study entry, and the registry entries do not support a claim that the intervention does or does not work.

The adverse-event counts provide descriptive information about events recorded in the study group. They do not, on their own, quantify risk relative to another treatment, establish causation, or resolve how events were distributed over time and across participants. The listed serious-event term percentages also lack a reported denominator in the available registry information. They should therefore be understood as registry summaries rather than as independently interpretable comparative estimates.

In general, a small feasibility study may inform whether a procedure is practicable and identify issues for further evaluation, but it cannot settle questions that require reliable comparative evidence. That general distinction is especially important for this single-group record: the design contains no like-for-like control, and the primary results are not reported. The available information supports describing the study design, endpoint criteria, and reported safety counts. It does not support conclusions about the magnitude of benefit, comparative safety, or longer-term outcomes.

14. Why This Trial Matters Statistically

This study is statistically notable because it separates a procedural feasibility question from a comparative treatment question. The primary endpoint asks whether a multi-part technical-success rule was satisfied at a defined procedural time point. That kind of endpoint can capture whether several steps and safety conditions were achieved, rather than reducing success to device deployment alone. Its interpretation depends on applying each criterion consistently, including the explicit rule that repositioning and recapture are not classified as failure.

The single-group design also clarifies the boundary of what a result could establish. A technical-success frequency, if reported, would describe the study participants and procedural setting. Without a concurrent comparator, it would not estimate a difference between TMCA and another approach. This distinction is fundamental in biostatistics: an outcome rate in one group and a treatment contrast answer different questions, even when they concern the same clinical procedure.

The record further illustrates the importance of outcome reporting. It contains endpoint definitions and safety counts, but no reported primary or secondary endpoint result and no statistical analysis. Readers cannot assess the observed technical-success frequency, its uncertainty, or how it relates to the secondary endpoint. A completed study record does not itself provide those missing estimates. Nor can a planning calculation replace an observed result or resolve the lack of a control group.

Finally, adverse-event summaries require careful interpretation. Counts describe reported participant-level categories, while causal attribution, timing, recurrence, and overlap require additional information. The registry's event counts are useful descriptive context, but not a comparative safety analysis. Together, these features make the study valuable to read as an early feasibility record while underscoring why transparent outcome and analysis reporting is necessary for stronger statistical conclusions.

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 are specific to the information recorded for this study. First, the registry record does not report the primary technical-success result or the secondary procedural-success result. Without these results, the central feasibility endpoint cannot be evaluated quantitatively. It is not possible to assess the observed frequency, the number of failures, or statistical uncertainty for either endpoint from this record.

Second, the study has a single group and no randomized or concurrent control comparison. Even complete outcome reporting would not establish a comparative effect against another procedure or care strategy. The enrollment of 19 participants also means that the study describes a limited cohort; the registry does not report enough participant characteristics to assess how broadly those observations might apply.

Third, the registry summary says the protocol was changed to allow people with mitral regurgitation despite prior Mitra-Clip treatment and people with symptomatic heart failure with mild mitral regurgitation. The record does not describe the timing or detailed implications of that change, nor does it provide subgroup results. It is therefore not possible to determine whether outcomes differed across those eligibility groups.

Finally, statistical and safety details are incomplete in the registry information. The analysis plan, analysis populations, missing-data rules, multiplicity approach, and sample-size justification are not reported. For adverse events, the available summaries do not specify timing, recurrence, participant-level overlap, or causal attribution; the denominator for the listed serious-event term percentages is not reported. These limitations restrict interpretation to the study description and recorded counts, rather than supporting a fuller assessment of outcomes or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: NHLBI DIR Transcatheter Mitral Cerclage Annuloplasty Early Feasibility Study — NCT03929913.
• Registry record last updated 2026-04-29; status last verified 2026-04.
• Results first posted 2023-03-08.
• 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

NCT03929913 is a completed, single-group early feasibility study of Transcatheter Mitral Cerclage Annuloplasty, with enrollment of 19 participants. The recorded study start date is 2019-05-07, and the primary completion date is 2021-02-23. The primary endpoint is technical success at exit from the catheterization laboratory; procedural success is listed as a secondary endpoint. The registry record does not report results for either endpoint or a statistical analysis.

For the intervention group, the record reports 12 participants with serious adverse events among 19 at risk, 19 with other adverse events among 19 at risk, and 5 deaths. The listed serious-event terms include Heart failure, Atrioventricular block complete, Hypotension, Acute kidney injury, Atrial fibrillation, and Encephalopathy. The study has no separate comparator group, and the registry does not report a trial-specific analysis plan or sample-size justification.